11 research outputs found
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Risk of Human Immunodeficiency Virus Type 1-Related Neurologic Disease in a Cohort of Intravenous Drug Users
Background: Although the proportion of cases of acquired immunodeficiency syndrome related to intravenous drug use has increased dramatically over the past decade, there has been no longitudinal examination of primary neurologic disease in this group. Objective: To study the development of neurologic disease in human immunodeficiency virus (HIV)—negative and HIV-positive men and women who were intravenous drug users over a 3.5-year period. Design: Prospective observational cohort study. Setting: Subjects were recruited from an infectious disease clinic at a New York City Hospital or from a methadone maintenance program. Participants: Ninety-nine HIV-negative (62 men and 37 women) and 124 HIV-positive (85 men and 39 women) intravenous drug users volunteered. Main Outcome Measure: The development of clinically significant manifestations in six neurologic domains. Results: With multivariate adjustment for current and past substance abuse, age, education, and head injury, we examined the odds of developing HIV-related neurologic disease. Extrapyramidal signs and reduced motor ability became increasingly apparent over time in HIV-infected men as their CD4 cell count declined and as the subjects developed the acquired immunodeficiency syndrome. Fewer neurologic signs were seen in the women. Conclusions: The impact of HIV infection among intravenous drug users parallels that in homosexual men and is independent of alcohol and other drug use
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Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users without Acquired Immunodeficiency Syndrome. Relationship to Head Injury
We examined 99 human immunodeficiency virus (HIV)—negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury
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Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users without Acquired Immunodeficiency Syndrome. Relationship to Head Injury
We examined 99 human immunodeficiency virus (HIV)—negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury
The landscape of genomic alterations across childhood cancers
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials