Pancreatic nociception – Revisiting the physiology and pathophysiology

BackgroundPain management of many pancreatic diseases remains a major clinical concern. This problem reflects our poor understanding of pain signaling from the pancreas.ObjectivesThis review provides an overview of our current knowledge, with emphasis on current pain management strategies and recent experimental findings.MethodsA systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965–2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses exploring pain and its management in disease states such as acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic cancer (PC).ResultsOver the last decade, numerous molecular mediators such as nerve growth factor and the transient receptor potential (TRP) cation channel family have been implicated in afferent nerve signaling. More recent animal studies have indicated the location of the receptive fields for the afferent nerves in the pancreas and shown that these are activated by agents including cholecystokinin octapeptide, 5-hydroxytryptamine and bradykinin. Studies with PC specimens have shown that neuro-immune interactions occur and numerous agents including TRP cation channel V1, artemin and fractalkine have been implicated. Experimental studies in the clinical setting have demonstrated impairment of inhibitory pain modulation from supraspinal structures and implicated neuropathic pain mechanisms.ConclusionsOur knowledge in this area remains incomplete. Characterization of the mediators and receptors/ion channels on the sensory nerve terminals are required in order to facilitate the development of new pharmaceutical treatments for AP and CP.     

A Higher Angiogenin Expression is Associated With a Nonnuclear Maspin Location in Laryngeal Carcinoma

Objectives

In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC).

Methods

Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes.

Results

On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression ≥5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression ≥5.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041).

Conclusion

Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.     

Evaluation of a Community Health Worker Intervention to Reduce HIV/AIDS Stigma and Increase HIV Testing Among Underserved Latinos in the Southwestern U.S.

Objectives

Latinos are at an elevated risk for HIV infection. Continued HIV/AIDS stigma presents barriers to HIV testing and affects the quality of life of HIV-positive individuals, yet few interventions addressing HIV/AIDS stigma have been developed for Latinos.

Methods

An intervention led by community health workers (promotores de salud, or promotores) targeting underserved Latinos in three southwestern U.S. communities was developed to decrease HIV/AIDS stigma and increase HIV knowledge and perception of risk. The intervention was led by HIV-positive and HIV-affected (i.e., those who have, or have had, a close family member or friend with HIV/AIDS) promotores, who delivered interactive group-based educational sessions to groups of Latinos in Spanish and English. To decrease stigma and motivate behavioral and attitudinal change, the educational sessions emphasized positive Latino cultural values and community assets. The participant pool comprised 579 Latino adults recruited in El Paso, Texas (n=204); San Ysidro, California (n=175); and Los Angeles, California (n=200).

Results

From pretest to posttest, HIV/AIDS stigma scores decreased significantly (p<0.001). Significant increases were observed in HIV/AIDS knowledge (p<0.001), willingness to discuss HIV/AIDS with one''s sexual partner (p<0.001), and HIV risk perception (p=0.006). Willingness to test for HIV in the three months following the intervention did not increase. Women demonstrated a greater reduction in HIV/AIDS stigma scores when compared with their male counterparts, which may have been related to a greater increase in HIV/AIDS knowledge scores (p=0.016 and p=0.007, respectively).

Conclusion

Promotores interventions to reduce HIV/AIDS stigma and increase HIV-related knowledge, perception of risk, and willingness to discuss sexual risk with partners show promise in reaching underserved Latino communities.Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has disproportionately affected U.S. Latinos during the last 25 years. Although Latinos constitute 16% of the U.S. population, they account for 19% of those living with HIV and 21% of new HIV infections.¹ Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended HIV testing for all people aged 13–64 years.² However, nearly half (46%) of Latino adults aged 18–64 years have never been tested, compared with 23% of black and 50% of white adults.³ Additionally, HIV testing often occurs at a late stage among HIV-positive Latinos. More than one-third (36%) of HIV-positive Latinos were diagnosed with AIDS within one year of learning their HIV status, compared with 32% of white people and 31% of black people.³ Late HIV testing hinders treatment options and may contribute to unknowing HIV transmission.Factors contributing to low HIV testing rates among Latinos include poverty, lack of health-care access, and limited availability of culturally and linguistically responsive services.^1,4–6 HIV/AIDS stigma is another factor.^7,8 UNAIDS (Joint United Nations Programme on AIDS) defines HIV stigma as the “devaluation of people either living with or associated with HIV/AIDS.”⁹ Stigma often results from fears about HIV as well as the associations of HIV with stigmatized groups such as homosexuals, sex workers, and injection drug users.^9,10HIV/AIDS stigma has negative consequences both at a population level and for individuals who are its targets, including people living with HIV/AIDS. Stigmatizing attitudes toward people living with HIV/AIDS are associated with decreased HIV testing, limited utilization of HIV prevention services, and high-risk sexual behaviors.^7,10,11 Additionally, for people living with HIV/AIDS, the stigma associated with HIV/AIDS contributes to unwillingness to disclose HIV status, unsafe sexual behaviors, delays in care seeking, reduced treatment adherence, mental health issues, and difficulties obtaining social support.^9,11–14Despite significant implications, few interventions have been developed to reduce HIV/AIDS stigma.^10,11,15 Existing interventions have often focused on specific populations (e.g., university students and health-care providers), with few interventions focused on Latinos,^11,15,16 who have high levels of stigmatizing attitudes toward people living with HIV/AIDS^1,17,18 that contribute to negative outcomes.^7,19Among Latinos, research indicates that community health workers (promotores de salud, hereinafter “promotores”) are an effective and culturally acceptable means of reaching the population with health information and motivating health behaviors.^20,21 Promotores are well positioned to promote changes in their communities because they share language and cultural values, are held in high esteem, and are perceived as role models.²¹ Promotores have been used to address health conditions ranging from chronic diseases to preventive screenings.^20–22 Several interventions have incorporated promotores into HIV prevention, finding significant changes in HIV risk behaviors, HIV counseling and testing, and other psychosocial constructs important to prevention.^16,23–29 To date, few studies have used promotores in interventions to reduce HIV stigma among Latinos.¹⁶We describe and report findings of an intervention using promotores to reduce HIV/AIDS stigma and increase willingness to seek HIV testing among Latinos in three communities in the southwestern United States: Los Angeles, California; San Ysidro, California; and El Paso, Texas.     

Worrisome Trend of New Multiple Mechanisms of Linezolid Resistance in Staphylococcal Clones Diffused in Italy

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).     

Autonomic cardiovascular alterations as therapeutic targets in chronic kidney disease

Clinical Autonomic Research - The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. We reviewed the...