Tumour-derived prostaglandin E2 and transforming growth factor-β synergize to inhibit plasmacytoid dendritic cell-derived interferon-α

In previous studies we reported that plasmacytoid dendritic cells (PDC) infiltrating head and neck cancer tissue are functionally impaired, but the molecular basis for the functional deficiency remained unclear. Here we demonstrate that tumour-derived prostaglandin E2 (PGE₂) and transforming growth factor-β (TGF-β) increase interleukin-8 (IL-8) but synergistically inhibit interferon-α (IFN-α) and tumour necrosis factor (TNF) production of Toll-like receptor 7 (TLR7)- and Toll-like receptor 9 (TLR9)-stimulated PDC. The inhibitory effect of PGE₂ could be mimicked by the induction of cyclic AMP (cAMP) and by inhibitors of cyclooxygenase. The contribution of tumour-derived TGF-β was confirmed by the TGF-β antagonist SB-431542. Suppression of tumour-derived PGE₂ and TGF-β restored TLR-induced IFN-α production of PDC. Additionally, PGE₂- and TGF-β-treated PDC display a ‘tolerogenic’ phenotype because of a downregulation of CD40 accompanied by an upregulation of CD86. Finally, in TLR-stimulated PDC, PGE₂ and TGF-β reduce the CCR7 : CXCR4 ratio, suggesting that PDC are impaired in their ability to migrate to tumour-draining lymph nodes but are retained in stromal cell-derived factor 1 (SDF-1)-expressing tissues. Based on these data, cyclooxygenase inhibitors and TGF-β antagonists may improve TLR7- and TLR9-based tumour immunotherapy.     

PDC expressing CD36, CD61 and IL-10 may contribute to propagation of immune tolerance

Human plasmacytoid dendritic cells (PDC) are blood dendritic cell antigen 2 (BDCA2) and blood dendritic cell antigen 4 (BDCA4) positive leukocytes that do not express common lineage markers. They have been described as proinflammatory innate immune cells and are the major source of αIFN in the human body. PDC-derived secretion of type I IFNs upon triggering of nucleic acid-sensing toll-like receptors (TLR) primes immune cells to rapidly respond to microbial stimuli and promotes a Th1 response. Here, we report that human PDC express CD36 and CD61 (β3 integrin), both involved in uptake of apoptotic cells and in induction of tolerance. Freshly isolated PDC and PDC within human blood leukocytes constitutively express IL-10. Thus, PDC may possess a so far neglected role in propagation of immune tolerance.     

Laryngeal edema: perioperative nursing considerations.

Laryngeal edema is a relatively rare yet serious postoperative complication for those patients undergoing general anesthesia. Maintenance of airway and breathing are always the first priority of perioperative patient care. Medical-surgical nurses working in postoperative settings must be familiar with the signs, symptoms, and necessary prompt treatment for this life-threatening condition.     

Examination of Routine Use of Prenatal Weight Gain Charts as a Communication Tool for Providers

Objectives In 2009 the IOM revised prenatal weight gain guidelines. The primary purpose of this pilot study was to assess if provider education and use of prenatal weight gain charts to track weight gain and counsel patients was associated with better patient and provider knowledge and communication about the guidelines. Methods A prospective non-randomized study conducted in four OB practices (two control, two intervention). Data sources included provider surveys (n?=?16 intervention, 21 control), patient surveys (n?=?332), and medical records. Intervention clinics received provider education on the IOM guidelines and used patient education materials and prenatal weight gain charts to track weight gain and as a counseling tool. Comparison clinics received no education and did not use the charts or patient education information. Results More patients at intervention clinics (92.3%) reported that a provider gave them advice about weight gain, compared to patients from comparison clinics (66.4%) (p?<?0.001). Intervention patients were also more likely to report satisfaction discussions with their provider about weight gain (83.1 vs. 64.3%, p?=?0.007). Intervention clinic patients were more likely to have knowledge of the guidelines indicated by 72.3% reporting a target weight gain amount within the guidelines versus 50.4% of comparison patients (p?<?0.001). Conclusion Provider education and use of weight gain charts resulted in higher patient reported communication about weight gain from their provider, higher patient satisfaction with those discussions, and better knowledge of the appropriate target weight gain goals.     

Posttraumatic Stress Disorder,Depression, and HIV Risk Behavior Among Ohio Army National Guard Soldiers

We examined the relationship between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and human immunodeficiency virus (HIV) risk behavior among the Ohio Army National Guard (OHARNG). We analyzed data collected from a sample of OHARNG enlisted between June 2008 and February 2009. Participants completed interviews assessing HIV risk activities defined by the Behavioral Risk Factor Surveillance System, and were screened for PTSD and MDD based on DSM‐IV criteria according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM‐IV; American Psychiatric Association, 1994). Logistic regression was used to examine the independent and combined effects of PTSD and MDD on past‐year HIV risk behavior. Of 2,259 participants, 142 (6.3%) reported at least 1 past‐year HIV risk behavior. In adjusted models, relative to soldiers with neither disorder, screening positive for MDD only was associated with HIV risk behavior (adjusted odds ratio [AOR] = 2.33, 95% CI = [1.15, 4.71]), whereas PTSD was not significant (AOR = 1.60, 95% CI = [0.80, 3.20]). Participants with both PTSD and depression were most likely to report HIV risk behavior (AOR = 2.75, 95% CI = [1.06, 7.11]). Soldiers with PTSD and MDD may be at greater risk for HIV infection due to increased engagement in HIV risk behavior. Integrated interventions to address mental health problems and reduce HIV risk behavior are in need of development and evaluation.     

Plasmapheresis in the treatment of hypertriglyceridemia‐induced pancreatitis: A community hospital's experience

Background: Hyperlipidemic pancreatitis is a potentially fatal complication of hypertriglyceridemia (HTG). The current mainstay of treatment for the hypertriglyceridemia associated with pancreatitis includes heparin, insulin and lipid lowering agents. Experiences with plasmapheresis are limited. Here, we report our experience using plasmapheresis in the treatment of four patients with acute severe HTG‐induced pancreatitis. Methods: Four patients with acute severe HTG‐induced pancreatitis due to severe primary hyperlipidemia exacerbated by secondary factors were studied. In addition to the standard treatment (insulin or heparin infusion), antibiotics and lipid lowering agents, two were treated within the first 48 hours, and two with early (<24 hours) plasmapheresis with 5% albumin. Results: All four patients had a significant improvement in their triglyceride levels using plasmapheresis with an average reduction in TG levels of 70.4% per treatment and 89.3% with the first treatment. However, there was no clear relation between the use of plasmapheresis and either improvement in APACHE II scores, length of stay in either the ICU or overall hospital length of stay or in the prevention of complications secondary to severe pancreatitis, including in the two patients who received plasmapheresis in the first 24 hours. Conclusion: Our report showed that plasmapheresis was successful in lowering TG levels. However, in the absence of a comparison with standard treatment (heparin or insulin infusion and lipid lowering agents) the effect of plasmapheresis on lowering the morbidity and length of stay of patients with HTG‐induced acute severe pancreatitis is uncertain and warrants further investigation into its efficacy. J. Clin. Apheresis 25:229–234, 2010. © 2010 Wiley‐Liss, Inc.     

The Asthma Outreach Project: A Promising Approach to Comprehensive Asthma Management

We describe a pilot system of coordinated asthma care emphasizing home visits by a community-based lay worker collaborating with a pediatrician, pharmacist, and public health nurse. Study participants included 23 low-income children with moderate to severe asthma and their families at an inner-city pediatric clinic. This system was successfully implemented, and client satisfaction was extremely high. Utilization review showed a reduction in hospitalizations, emergency department visits, and unscheduled clinic visits, and an increase in follow-up clinic visits. This model of care may reduce unscheduled service use and deserves further study as an alternative for asthma management among similar patient populations.