Dermatologic manifestations of AIDS in children

A wide variety of clinical expressions of the acquired immunodeficiency syndrome (AIDS) has been apparent from the earliest case reports in adult patients and pediatric patients. Both human immunodeficiency virus (HIV) infection and AIDS in children are associated with an increased prevalence of several dermatologic manifestations. In this article we present a review of the recent literature describing the cutaneous manifestations of pediatric AIDS. The cutaneous manifestations of AIDS in children can be divided into three categories: (1) neoplastic manifestations; (2) viral, bacterial and fungal manifestations, and (3) vascular lesions and other manifestations. Pediatricians as well as dermatologists may be the first physicians to recognize and to treat the clinical manifestations of AIDS.     

Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-γ, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ± 2.8 pg/ml; controls, 3.2 ± 0.7 pg/ml) and IFN-γ (39.2 ± 67.6 pg/ml; controls, 8.4 ± 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ± 2.6 pg/ml), whereas IFN-γ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ± 200.4 pg/ml and 56.6 ± 38.4 pg/ml, respectively; controls, 17.4 ± 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ± 1.2 pg/ml; controls, 2.4 ± 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ± 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-γ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human immunodeficiency virus type 1 infection

Dysfunction of neutrophils (polymorphonuclear leukocytes [PMNL]) and macrophagic cells occurs as a consequence of human immunodeficiency virus type 1 (HIV-1) infection. Macrophages contribute to the resolution of early inflammation ingesting PMNL apoptotic bodies. This study investigated macrophage ability to phagocytose PMNL apoptotic bodies in patients with HIV-1 infection in comparison with uninfected individuals and the effect of HIV Nef protein on apoptotic body phagocytosis to determine if phagocytic activity is impaired by HIV infection. Monocytes/macrophages were isolated from 10 HIV-1-infected patients and from five healthy volunteers, whereas PMNL were isolated from healthy volunteers. Macrophage phagocytosis of apoptotic PMNL was determined by staining of apoptotic bodies with fluorescein-conjugated concanavalin A or with fluorescein-labeled phalloidin. Our data show significant impairment of PMNL apoptotic body macrophage phagocytosis in subjects with HIV-1 infection presenting a concentration of CD4(+) T lymphocytes of >200/mm(3) and in particular in those with <200 CD4(+) T lymphocyte cells/mm(3). In addition, HIV-1 recombinant Nef protein is able to decrease phagocytosis of apoptotic PMNL from normal human macrophages in a dose-dependent manner. The results of our study suggest that impaired macrophage phagocytosis of PMNL apoptotic bodies may contribute to the persistence of the inflammatory state in HIV-infected subjects, especially during opportunistic infections that are often favored by defective phagocytic activity.     

Cytokines and anorexia nervosa

OBJECTIVE: Recent studies have indicated that the inflammatory cytokines could be implicated in anorexia nervosa and in its complications. To determinate the potential role of interleukins (IL-1, IL-2, IL-4, IL-6, IL-10), interferon (IFN gamma), tumor necrosis factor (TNF-alpha), and transforming growth factor (TGF-beta2) in anorexia nervosa, serum concentrations of these cytokines were measured in patients suffering from anorexia nervosa in comparison to healthy subjects. METHOD: Twenty-nine anorexic women according to DSM-IV criteria participated in the study. The control group consisted of 20 healthy women without eating disorders, mood disorders, and immunological disorders. RESULTS: We find that serum IL-2 and TGF-beta2 concentrations were both significantly decreased in anorexic patients, although the other cytokines did not differ significantly between the two groups. CONCLUSION: Our results show that in patients with anorexia nervosa, there are lower levels of specific cytokines (especially IL-2 and TGF-beta2). These levels may reflect the combination of impaired nutrition and weight loss, therefore, the dysregulation of these cytokines may contribute in anorexia's complications. Follow-up studies should examine the effects of parameters such as starvation, psychopathologic factors, and psychoneuroendocrinological perturbation which could affect interplay between cytokines, neuropeptides, and neurotransmitters.     

Meningoencephalitis caused by human herpesvirus-6 in an immunocompetent adult patient: Case report and review of the literature

Summary Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, and has been implicated as a possible cause of encephalitis in pediatric and adult patients. A case of meningoencephalitis in an otherwise healthy, immunocompetent 59-year-old woman is described. The diagnosis of HHV-6 meningoencephalitis was confirmed by detecting viral DNA in cerebrospinal fluid collected in the acute stage of the disease by polymerase chain reaction. The patient was treated with acyclovir and recovered without any sequelae. The current knowledge of the pathophysiology, clinical course and outcome of HHV-6 meningoencephalitis in immunocompetent adult patients is also reviewed.     

Histone deacetylase 6 inhibition enhances oncolytic viral replication in glioma

Oncolytic viral (OV) therapy, which uses genetically engineered tumor-targeting viruses, is being increasingly used in cancer clinical trials due to the direct cytolytic effects of this treatment that appear to provoke a robust immune response against the tumor. As OVs enter tumor cells, intrinsic host defenses have the potential to hinder viral replication and spread within the tumor mass. In this report, we show that histone deacetylase 6 (HDAC6) in tumor cells appears to alter the trafficking of post-entry OVs from the nucleus toward lysosomes. In glioma cell lines and glioma-stem–like cells, HDAC6 inhibition (HDAC6i) by either pharmacologic or genetic means substantially increased replication of oncolytic herpes simplex virus type 1 (oHSV). Moreover, HDAC6i increased shuttling of post-entry oHSV to the nucleus. In addition, electron microscopic analysis revealed that post-entry oHSVs are preferentially taken up into glioma cells through the endosomal pathway rather than via fusion at the cell surface. Together, these findings illustrate a mechanism of glioma cell defense against an incoming infection by oHSV and identify possible approaches to enhance oHSV replication and subsequent lysis of tumor cells.     

An Investigation of Goodman's Addictive Disorder Criteria in Eating Disorders

The aim of this study was to examine how far Goodman's addictive disorder criteria were met by individuals with eating disorders according to subtypes. The study provided a cross‐sectional comparison among three samples of eating disorders [restricting anorexia nervosa (R‐AN), N = 68; purging anorexia nervosa (P‐AN), N = 42; and bulimia nervosa (BN), N = 66], a sample of substance‐related disorders (SRDs, N = 48) and a sample of matched controls (N = 201). Diagnosis of addictive disorder was made following Goodman's criteria. Addictive personality traits were assessed with the Addiction Potential Scale of the Minnesota Multiphasic Personality Inventory—2 and with the Zuckerman's Sensation Seeking Scale. Results showed that individuals with BN met Goodman's addictive disorder criteria in the same proportion as drug‐addicted individuals (65% vs 60%, p = NS). They both showed higher rates than R‐AN individuals (35%; R‐AN versus BN: F = 11.9, p < 0.001 and R‐AN versus SRD: F = 7.16, p < 0.01). Although BN and SRD showed higher rates of addictive disorders compared with P‐AN, differences were not significant. Scores on the Sensation Seeking and on the Addictive Potential scales paralleled the distribution of addictive disorders, with individuals with BN and with P‐AN showing higher levels than individuals with R‐AN. Results showed that a subgroup of individuals with an eating disorder experiences their disorder as an addiction and may deserve specific therapeutic attention. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.