Interferon-Inducible Protein-10 and the Pathogenesis of Cutaneous T-Cell Lymphomas

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.     

Fever of unknown origin in patients with HIV infection in Thailand: an observational study and review of the literature

Fever of unknown origin (FUO) is a common presentation for patients with advanced human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). We prospectively followed 72 patients, consecutively admitted to a Thai regional hospital with FUO and HIV infection to identify aetiologies and mortality in the era of available antiretroviral therapy (ART). Aetiologies of FUO were identified in 67 patients (93%), of whom 61(85%) had an infectious aetiology. The most common infectious aetiologies were Mycobacterium tuberculosis (n=30; 42%), Cryptococcus neoformans (n=17; 24%), Pneumocystis jiroveci (n=9; 13%), Toxoplasma gondii (n=5; 7%), and salmonella bacteraemia (n=5; 7%). Nineteen patients (26%) had co-infection with two or more pathogens. The median CD4 count was 120 cells/mm(3) (range, 1-581 cells/mm(3)), and the all-cause mortality was 22% (n=16). By multivariate analysis, inadequate antimicrobial treatment was the sole predictor of mortality (aOR=4.9; 95% CI=1.2-21.9; P=0.02). Overall, 58 of 72 patients (81%) had an opportunistic infection suggesting that guideline use of ART and prophylactic strategies remain unmet needs that will benefit individuals and populations with HIV/AIDS in Thailand.     

Moral professional personhood: ethical reflections during initial clinical encounters in nursing education

Moral agency is an important constituent of the nursing role. We explored issues of ethical development in Greek nursing students during clinical practice at the beginning of their studies. Specifically, we aimed to explore students' lived experience of ethics, and their perceptions and understanding of encountered ethical conflicts through phenomenological analysis of written narratives. The process of developing an awareness of personal values through empathizing with patients was identified as the core theme of the students' experience. Six more common themes were identified. Development of the students' moral awareness was conceptualized as a set of stages, commencing with empathizing with patients and nurses, moving on to taking a moral stand and, finally, concluding by becoming aware of their personal values and showing evidence of an emerging professional moral personhood. The notions of empathy, caring and emotion were in evidence throughout the students' experience. Implications for practice and nurse education are discussed.     

Seasonal variation in the epidemiology of sepsis

OBJECTIVE: We sought to investigate seasonal and regional variability in the epidemiology of sepsis and to identify underlying associations based on geography and seasonal viral infections. Understanding seasonal or regional variations may improve knowledge of sepsis epidemiology and pathophysiology and could affect healthcare planning and resource allocation. DESIGN: Retrospective cohort study using the National Hospital Discharge Survey to identify cases of sepsis, severe sepsis, influenza, and viral pneumonia using ICD-9-CM codes. Incidence rates are reported as mean cases frequencies per season per 100,000 as calculated by normalization to the 2000 U.S. Census. SETTING: Acute-care nonfederal U.S. hospitals. PATIENTS: Patients hospitalized between 1979 and 2003 in acute-care nonfederal U.S. hospitals with a diagnosis of sepsis or viral respiratory infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The seasonal incidence rate of sepsis increased 16.5% from a low of 41.7 in the fall to a high of 48.6 cases per 100,000 in the winter (p<.05). Similarly, seasonal rates for severe sepsis statistically increased 17.7% from fall to winter at 13.0 and 15.3 cases per 100,000, respectively. The greatest change in sepsis incidence occurred with respiratory sources, increasing 40% during the winter compared with the fall (p<.05). Seasonal variations in viral respiratory infections paralleled changes in sepsis incidence but did not fully account for the changes. The greatest seasonal change in sepsis rates occurred in the Northeast (+30%). Sepsis case-fatality rates were 13% greater in the winter compared with the summer (p<.05) despite similar severity of illness. CONCLUSIONS: The incidence and mortality of sepsis and severe sepsis are seasonal and consistently highest during the winter, predominantly related to respiratory sepsis. Seasonal changes in sepsis incidence vary according to geographic region. The mechanisms underlying these differences require further investigation.     

Superficial cortical siderosis

Cerebrovascular deposition of amyloid (cerebral amyloid angiopathy CAA) is most commonly recognized as a cause of spontaneous lobar intracerebral hemorrhage. On the basis of the noninvasive new MR imaging we would propose superficial cortical hemosiderosis and subarachnoid hemosiderosis as potentially useful new criteria to facilitate the diagnosis of CAA.     

Dissociable functional connectivity changes during the Stroop task relating to risk, resilience and disease expression in bipolar disorder

Reduced cognitive control is considered a core feature of bipolar disorder (BD). Abnormalities in ventrolateral prefrontal cortex (VLPFC) and other functionally linked regions that underpin cognitive control during the Stroop Colour Word Task (SCWT) have been reported in patients with BD and their relatives. In this functional magnetic resonance study we used psychophysiological interaction analysis to examine functional connectivity during the SCWT in 39 euthymic BD patients, 39 of their first-degree relatives (25 with no Axis I disorders and 14 with major depressive disorder) and 48 healthy controls. The aim of this study was to identify potential diagnosis-specific functional connectivity changes differentiating patients with BD from their relatives with MDD, as well as functional connectivity correlates of resilience in relatives of BD patients who remain well. Psychophysiological interactions in healthy controls revealed a negative functional connectivity between the VLPFC and the ventral anterior cingulate cortex and insula and a positive connectivity between the VLPFC and the caudate and parietal cortices. Abnormalities in fronto-insular connectivity emerged as a key correlate of predisposition and disease expression for BD. Reduced fronto-cingulate connectivity was also observed in association with predisposition to BD irrespective of clinical outcome. BD patients and their MDD relatives showed additional abnormalities in frontal-basal ganglia connectivity while increased coupling between the ventral and dorsal lateral PFC was observed in relatives without any Axis I disorder. These findings suggest that during the SCWT the VLPFC and subcortical regions are involved in a dynamic interplay. Breakdown in these interactions is associated with risk and disease expression for mood disorders while increased functional coupling between dorsal and ventral prefrontal regions may reflect adaptive functional changes associated with resilience.     

Sex differences in bipolar disorder: a review of neuroimaging findings and new evidence

Jogia J, Dima D, Frangou S. Sex differences in bipolar disorder: a review of neuroimaging findings and new evidence.
Bipolar Disord 2012: 14: 461–471. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The sex of an individual is known to modulate the clinical presentation of bipolar disorder (BD), but little is known as to whether there are significant sex‐by‐diagnosis interactions on the brain structural and functional correlates of BD. Methods: We conducted a literature review of magnetic resonance imaging (MRI) studies in BD, published between January 1990 and December 2010, reporting on the effects of sex and diagnosis. In the absence of any functional MRI (fMRI) studies, this review was supplemented by original data analyses focusing on sex‐by‐diagnosis interactions on patterns of brain activation obtained during tasks of working memory, incentive decision‐making, and facial affect processing. Results: We found no support for a sex‐by‐diagnosis interaction in global gray or white matter volume. Evidence regarding regional volumetric measures is limited, but points to complex interactions between sex and diagnosis with developmental and temperamental factors within limbic and prefrontal regions. Sex‐by‐diagnosis interactions were noted in the pattern of activation within the basal ganglia during incentive decision‐making and within ventral prefrontal regions during facial affect processing. Conclusions: Potential sex‐by‐diagnosis interactions influencing the brain structural and functional correlates of disease expression in BD have received limited attention. Our data suggest that the sex of an individual modulates structure and function within subcortical and cortical regions implicated in disease expression.     

Polyclonal Outbreak of Vancomycin-resistant Enterococcus faecium in a Pediatric Oncology Department

We present a polyclonal outbreak of vancomycin-resistant enterococci (VRE) colonization in a pediatric oncology department and the role of a bundle of actions. After the occurrence of VRE bloodstream infections in 2 patients, an active surveillance of VRE colonization was started. Enhanced infection control measures and closure of the department to new admissions for the first 3 months were implemented. Among 32 patients screened for VRE, 21 were found colonized. Daily prevalence of VRE colonization among hospitalized patients ranged from 40% to 75%, but no new VRE infections occurred. Monthly incidence of VRE colonization decreased from 2.5 to 0.6 cases per 100 occupied bed-days at the end of this outbreak by the implementation of the above-mentioned measures. All VRE isolates tested were Enterococcus faecium carrying VanA gene. Pulsed field gel electrophoresis showed a polyclonal outbreak. A case-control study did not show any particular risk factors for colonization. High use of glycopeptide was noted before study outbreak that was drastically decreased during the study but only temporarily. Control of VRE in pediatric oncology departments with high colonization rates is challenging and requires a multifaceted strategy. Polyclonal spread of VRE found in this study suggests a possible effect of prior antimicrobial overuse and the critical need for antimicrobial stewardship especially in the era of multidrug-resistant bacteria.