Role of Paris PM2.5 components in the pro-inflammatory response induced in airway epithelial cells

Particulate matter (PM) is suspected to play a role in environmentally-induced pathologies. Due to its complex composition, the contribution of each PM components to PM-induced biological effects remains unclear.     

Patterns of hippocampal–neocortical interactions in the retrieval of episodic autobiographical memories across the entire life‐span of aged adults

We previously demonstrated that episodic autobiographical memories (EAMs) rely on a network of brain regions comprising the medial temporal lobe (MTL) and distributed neocortical regions regardless of their remoteness. The findings supported the model of memory consolidation, which proposes a permanent role of MTL during EAM retrieval (multiple‐trace theory or MTT) rather than a temporary role (standard model). Our present aim was to expand the results by examining the interactions between the MTL and neocortical regions (or MTL–neocortical links) during EAM retrieval with varying retention intervals. We used an experimental paradigm specially designed to engage aged participants in the recollection of EAMs, extracted from five different time‐periods, covering their whole life‐span, in order to examine correlations between activation in the MTL and neocortical regions. The nature of the memories was checked at debriefing by means of behavioral measures to control the degree of episodicity and properties of memories. Targeted correlational analyses carried out on the MTL, frontal, lateral temporal, and posterior regions revealed strong links between the MTL and neocortex during the retrieval of both recent and remote EAMs, challenging the standard model of memory consolidation and supporting MTT instead. Further confirmation was given by results showing that activation in the left and right hippocampi significantly correlated during the retrieval of both recent and remote memories. Correlations among extra‐MTL neocortical regions also emerged for all time‐periods, confirming the critical role of the prefrontal, temporal (lateral temporal cortex and temporal pole), precuneus, and posterior cingulate regions in EAM retrieval. Overall, this paper emphasizes the role of a bilateral network of MTL and neocortical areas whose activation correlate during the recollection of rich phenomenological recent and remote EAMs. © 2009 Wiley‐Liss, Inc.     

Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation

OBJECTIVE: Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance. METHODS: The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery. CONCLUSION: The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term.     

Genetic polymorphisms and resistance mutations of HIV type 2 in antiretroviral-naive patients in Burkina Faso

Natural polymorphisms in the pol gene of HIV-2 may influence the susceptibility to antiretroviral drugs and the choice of treatment. We collected samples in centers for anonymous HIV testing in Ouagadougou, Burkina Faso, in patients supposedly naive for any antiretroviral treatment. Eighty-four samples were first tested as HIV-2 positive in Burkina Faso and then shipped to Brussels, Belgium, for confirmation of the serological status and plasma viral load. Fifty-two samples were confirmed as HIV-2 positive in Belgium. Twelve others were HIV-1 positive and 20 were dually reactive. Twenty-one of HIV-2 confirmed samples had an HIV-2 plasma viral load higher than 1000 copies/ml. These viruses were sequenced in the protease and reverse trancriptase genes and 17 sequences of the pol gene were obtained. Highly polymorphic positions were identified in protease and RT genes. Two samples harbored known resistance mutations: M184V RT mutation in one and Q151M with M184V in the other. Phylogenetic analysis showed that viruses in Burkina Faso did not cluster separately from published sequences from neighboring countries. The two resistant strains were unrelated. Our findings imply either that resistant viruses are circulating in Burkina Faso or that some individuals take unsupervised treatment. Both hypotheses present problems.     

Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study

Introduction

Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI).

Methods

In 217 patients with sustained hypotension, enrolled and followed prospectively, we compared the evolution of the mean arterial pressure (MAP) during the first 24 hours between patients who will show AKI 72 hours after inclusion (AKI_h72) and patients who will not. AKI_h72 was defined as the need of renal replacement therapy or "Injury" or "Failure" classes of the 5-stage RIFLE classification (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) for acute kidney insufficiency using the creatinine and urine output criteria. This comparison was performed in four different subgroups of patients according to the presence or not of AKI at the sixth hour after inclusion (AKI_h6 as defined as a serum creatinine level above 1.5 times baseline value within the first six hours) and the presence or not of septic shock at inclusion.The ability of MAP averaged over H6 to H24 to predict AKI_h72 was assessed by the area under the receiver operating characteristic curve (AUC) and compared between groups.

Results

The MAP averaged over H6 to H24 or over H12 to H24 was significantly lower in patients who showed AKI_h72 than in those who did not, only in septic shock patients with AKI_h6, whereas no link was found between MAP and AKI_h72 in the three others subgroups of patients. In patients with septic shock plus AKI_h6, MAP averaged over H6 to H24 or over H12 to H24 had an AUC of 0.83 (0.72 to 0.92) or 0.84 (0.72 to 0.92), respectively, to predict AKI_h72 . In these patients, the best level of MAP to prevent AKI_h72 was between 72 and 82 mmHg.

Conclusions

MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.     

Six-month prognosis of patients with lung cancer admitted to the intensive care unit

Background

Intensive care unit (ICU) admission of patients with lung cancer remains debated because of the poor short-term prognosis. However, ICU admission of such patients should also be assessed on the possibility to administer specific anticancer treatment and the long-term outcome thereafter.

Objectives

To identify predictive factors of hospital and 6-month mortality in critically ill lung-cancer patients.

Design and setting

Retrospective study conducted in the ICU of a university hospital.

Patients

One hundred five consecutive lung-cancer patients included between 1 January 1997 and 31 December 2006.

Interventions

None.

Results

Of the 105 patients (mean age 64.8 years), 87 (83%) had a non-small cell lung cancer (NSCLC). Extensive disease was diagnosed in 85 patients (83%) (NSCLC stages IIIB and IV or disseminated small cell lung cancer). The main reasons for ICU admission were acute respiratory failure (59%) and/or hemoptysis (45%). Forty-three patients (41%) needed mechanical ventilation (MV). The ICU, hospital and 6-month mortality rates were 43, 54 and 73%, respectively. A performance status (PS) ≥2 [odds ratio OR = 3.6 (95% confidence interval CI (1.5–8.7)] and acute respiratory failure [OR = 3.5 (95% CI (1.5–8.4)] predicted hospital mortality. In a multivariate Cox model, the cancer progression [hazard ratio HR = 6.1 (95% CI 2.2–17)] and the need for MV [HR = 3.6 (95% CI 1.35–9.4)] were independently associated with 6-month mortality. Two-thirds of the ICU survivors were able to receive anticancer treatment.

Conclusions

ICU admission should be considered in selected patients with lung cancer (PS <2, no cancer disease progression).