50 research outputs found

    Should you test for H pylori in patients with nonulcer dyspepsia?

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    Helicobacter pylori in creases the risk of developing peptic ulcer disease (strength of recommendation [SOR]: B, cohort study), but there is no evidence that treating H pylori reduces that risk. Treating H pylori in patients with nonulcer dyspepsia reduces symptoms, but doesn't improve quality of life in the short term (SOR: B, systematic review of randomized controlled trials [RCTs] with inconsistent results), but may alleviate symptoms in the long term (SOR: B, RCT with methodological flaws). Eradicating H pylori is relatively inexpensive (SOR: A, systematic review of economic analyses)

    Congestive heart failure: therapeutics--chronic CHF

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    This issue of eMedRef provides information to clinicians on the therapeutics of chronic congestive heart failure

    Adenovirus vector delivery stimulates natural killer cell recognition

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    We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8+ T cells. Significantly, γ-irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery

    Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis

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    Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity

    Maintenance of Hair Follicle Immune Privilege Is Linked to Prevention of NK Cell Attack

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    Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56+/NKG2D+ NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56+/NKG2D+ NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56+ NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management

    SARS Surveillance during Emergency Public Health Response, United States, March–July 2003

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    In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology

    Reducing Smoking Cessation Disparities: Capacity for a Primary Care- and Technology-Based Approach Among Medicaid Recipients

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    While cigarette use among U.S adults has recently decreased, vulnerable subgroups continue to smoke at high rates, including individuals receiving Medicaid insurance. These individuals have also experienced treatment access disparities, highlighting the need for approaches that leverage their strong desire to quit. We conducted interviews with 100 adult primary care patients receiving Medicaid who were current tobacco users about their use, openness to technology-based interventions, and readiness to change. Most (92%) reported current cigarette use and readiness to change averaged 6.98 out of 10 (SD = 2.82). Nearly all were open to completing an iPad-based tobacco screening (95%) and brief intervention (90%) at their next appointment, while 91% and 88% were willing to talk with their provider or a cessation counselor, respectively, about the subsequent results. Results persisted across age, sex, and race/ethnicity. Openness to technology-based interventions in this population provides support for future work that may ultimately reduce disparities
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