The role of neutrophils in severe sepsis

Neutrophils are key effectors of the innate immune response. Reduction of neutrophil migration to infection sites is associated with a poor outcome in sepsis. We have demonstrated a failure of neutrophil migration in lethal sepsis. Together with this failure, we observed more bacteria in both peritoneal exudates and blood, followed by a reduction in survival rate. Furthermore, neutrophils obtained from severe septic patients displayed a marked reduction in chemotactic response compared with neutrophils from healthy subjects. The mechanisms of neutrophil migration failure are not completely understood. However, it is known that they involve systemic Toll-like receptor activation by bacteria and/or their products and result in excessive levels of circulating cytokines/chemokines. These mediators acting together with LPS stimulate expression of iNOS that produces high amounts of NO, which in turn mediates the failure of neutrophil migration. NO reduced expression of CXCR2 on neutrophils and the levels of adhesion molecules on both endothelial cells and neutrophils. These events culminate in decreased endothelium-leukocyte interactions, diminished neutrophil chemotactic response, and neutrophil migration failure. Additionally, the NO effect, at least in part, is mediated by peroxynitrite. In this review, we summarize what is known regarding the mechanisms of neutrophil migration impairment in severe sepsis.

Inhibition of Neutrophil Migration by Hemopexin Leads to Increased Mortality Due to Sepsis in Mice

Rationale: The reduction of neutrophil migration to the bacterial focus is associated with poor outcome in sepsis. Objectives: The objective of this study was to identify soluble substances in the blood of septic mice that inhibit neutrophil migration. Methods: A pool of serum obtained from mice 2 hours after the induction of severe sepsis by cecal ligation and puncture inhibited the neutrophil migration. The proteins with inhibitory activity on neutrophil migration were isolated by Blue-Sepharose chromatography, high-performance liquid chromatography, and electrophoresis, and identified by mass spectrometry. Measurements and Main Results: Hemopexin was identified as the serum component responsible for the inhibition of neutrophil migration. In sepsis, the pretreatment of wild-type mice with hemopexin inhibited neutrophil migration to the focus of infection and decreased the survival rate from 87.5 to 50.0%. Hemopexin-null mice subjected to severe sepsis presented normal neutrophil migration, low bacteremia, and an improvement of 40% in survival rate. Moreover, hemopexin inhibited the neutrophil chemotaxis response evoked by C5a or macrophage inflammatory protein-2 and induced a reduction of CXCR2 and L-selectin as well as the up-regulation of CD11b expression in neutrophil membranes. The inhibitory effect of hemopexin on neutrophil chemotaxis was prevented by serine protease inhibitors or ATP. In addition, serum levels of ATP were decreased 2 hours after severe sepsis. Conclusions: These data demonstrate for the first time the inhibitory role of hemopexin in neutrophil migration during sepsis and suggest that the therapeutic inhibition of hemopexin or its protease activity could improve neutrophil migration to the focus of infection and survival in sepsis.

Anti-mullerian hormone is the best predictor of poor response in ICSI cycles of patients with endometriosis

Purpose: To correlate ovarian reserve (OR) markers with response in assisted reproduction techniques (ART) and determine their ability to predict poor response among patients with endometriosis (EDT). Methods: We evaluated ART cycles of 27 women with EDT and 50 with exclusive male factor. Basal follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) levels were determined. Ovarian response to gonadotropin stimulation was assessed and correlation coefficients calculated between the variables and reserve markers. Areas under the curve (AUC) determined ability of tests to predict poor response. Results: AMH was significantly correlated with response in both groups and it was the only marker with significant discriminative capacity to predict poor response among EDT (AUC = 0.842; 95% CI: 0.651-0.952) and control group (AUC = 0.869; 95% CI: 0.743-0.947). Conclusion: Infertile patients with endometriosis can benefit from the pre-therapeutic assessment of OR markers. However, regardless of disease presence, only AMH predicts poor response to stimulus.

Risk of Potential Drug-Drug Interactions among Brazilian Elderly A Population-Based, Cross-Sectional Study

Background: Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives: To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods: A population-based cross-sectional study was carried out involving 2143 elderly (aged 60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results: Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >= 75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions: Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

Temporal distribution of trauma deaths: Quality of trauma care in a developing country

Background: Examination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care. Objective: The purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas. Methods: We analyzed the National Health Minister`s System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001. Results. During the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%). Conclusions: The region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Tuberculosis among health care workers in a Brazilian tertiary hospital emergency unit

The Brazilian emergency system is being reorganized as a hierarchy in the region of Ribeirao Preto, state of Sao Paulo. We found increased occupational risk for tuberculosis in this region tertiary reference center-a nurse technician (Incidence rate [IR] 526.3/100000 inhabitants) had a risk of tuberculosis 12.6 (95% confidence interval [CI], 2.57-37.23) greater than the city population (41.8/100000 inhabitants). The system reorganization will have to make the centers adequate to deal with this problem. (C) 2008 Elsevier Inc. All rights reserved.

Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

Study of the Discriminative Validity of the PHQ-9 and PHQ-2 in a Sample of Brazilian Women in the Context of Primary Health Care

PURPOSE. This study aimed to assess the discriminative validity of the Brazilian version of the Patient Health Questionnaire (PHQ-9) and of its reduced version (PHQ-2). DESIGN AND METHODS. The sample consisted of 177 women (60 cases of depression and 117 noncases). The SCID-IV was used as the gold standard. FINDINGS. For the PHQ-9, a cutoff score equal to or higher than 10 proved to be the most adequate for the screening of depression, whereas the best cutoff score for the PHQ-2 was found to lie between 3 and 4. PRACTICE IMPLICATIONS. The systematic use of these instruments in nursing and in the context of primary health care could favor the early detection of depression.