Masashi Rotte

Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo.

We studied here the long-term maintenance of distinct populations of T helper type 1 (TH1)-lineage cells in vivo and found that effector TH1 cells, defined by their secretion of interferon-γ (IFN-γ), are short-lived and do not efficiently develop into long-term memory TH1 cells. In contrast, a population of activated TH1-lineage cells that did not secrete IFN-γ after primary antigenic stimulation persisted for several months in vivo and developed the capacity to secrete IFN-γ upon subsequent stimulation. These data suggest that a linear differentiation pathway, as defined by the transition from IFN-γ–producing to resting memory cells, is relatively limited in vivo and support a revised model for TH1 memory differentiation.

IL-10 Is Required for Optimal CD8 T Cell Memory following Listeria monocytogenes Infection

IL-10 is an important immunoregulatory cytokine that plays a central role in maintaining a balance between protective immunity against infection and limiting proinflammatory responses to self or cross-reactive Ags. We examined the full effects of IL-10 deficiency on the establishment and quality of T cell memory using murine listeriosis as a model system. IL-10−/− mice had reduced bacterial loads and a shorter duration of primary infection than did wild-type mice. However, the number of Ag-specific T cells in secondary lymphoid and nonlymphoid organs was diminished in IL-10−/− mice, compared with wild-type mice, at the peak of the effector response. Moreover, the frequency and protective capacity of memory T cells also were reduced in IL-10−/− mice when assessed up to 100 days postinfection. Remarkably, this effect was more pronounced for CD8 T cells than CD4 T cells. To address whether differences in the number of bacteria and duration of primary infection could explain these findings, both strains of mice were treated with ampicillin 24 hours after primary infection. Despite there being more comparable bacterial loads during primary infection, IL-10−/− mice still generated fewer memory CD8 T cells and were less protected against secondary infection than were wild-type mice. Finally, the adoptive transfer of purified CD8 T cells from previously infected wild-type mice into naive recipients conferred better protection than the transfer of CD8 T cells from immune IL-10−/− mice. Overall, these data show that IL-10 plays an unexpected role in promoting and/or sustaining CD8 T cell memory following Listeria monocytogenes infection.

IFN-γ Mediates the Death of Th1 Cells in a Paracrine Manner

Th1 cells have different capacities to develop into memory cells based on their production of IFN-γ. In this study, the mechanism by which a homogenous population of IFN-γ-producing CD4 T cells was eliminated in vivo was assessed. When such cells were transferred into naive mice and activated with Ag, a striking decrease in the frequency of cells in the spleen and lung was observed. However, administration of neutralizing anti-IFN-γ Ab at the time of Ag challenge largely prevented the elimination of such cells. To determine whether IFN-γ was mediating its effects directly and/or indirectly, the ability of IFN-γ to effectively signal in such cells was assessed in vitro. Indeed, there was reduced phosphorylation of STAT1 in response to IFN-γ as well as markedly reduced expression of the IFN-γR β-chain. Furthermore, transfer of such cells into IFN-γR-deficient mice limited their death following activation with Ag. Together, these data suggest that IFN-γ acts in a paracrine manner to mediate the death of activated IFN-γ-producing Th1 cells. In contrast to Ag stimulation, administration of CpG alone resulted in the elimination of Th1 cells in IFN-γR−/− mice. These results show that in response to Ag stimulation, the death of IFN-γ-producing effector Th1 cells is controlled in an IFN-γ-dependent manner, whereas in response to innate activation, the death of IFN-γ-producing Th1 cells can occur through an IFN-γ-independent pathway. Collectively, these data show the multiple mechanisms by which Th1 effector cells are efficiently eliminated in vivo.

Soft Tissue Foreign Body Removal Technique Using Portable Ultrasonography

Retained foreign objects account for as much as 2% of soft tissue injuries sustained in the wilderness. Subcutaneously embedded fragments are often missed during the initial medical evaluation and may result in morbidity secondary to delayed removal. Although the utility of ultrasonography in the emergency department for the detection of retained objects is established, the potential use of point-of-care ultrasound to aid with foreign body removal in the field has not been well described. We present 2 case reports that demonstrate the value of ultrasonography in detecting and successfully removing foreign bodies sustained in the wilderness, and outline a procedural technique that minimizes morbidity and uses equipment available in wilderness medical field kits. We propose that with the advent of portable and handheld ultrasound units, foreign body removal in the field has become feasible and may decrease the morbidity of soft tissue injuries, particularly in austere and wilderness environments with limited access to immediate medical care.

Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the FcεRI β subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on FcεRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of FcεRI β and γ subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating FcεRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the FcεRI β subunit is a crucial step in the initiation of FcεRI signaling and that Lyn is limiting for FcεRI-induced secretion of inflammatory mediators.

Resuscitation of the pregnant patient: What is the effect of patient positioning on inferior vena cava diameter? ,

STUDY OBJECTIVE Patients in the third trimester of pregnancy presenting to the emergency department (ED) with hypotension are routinely placed in the left lateral tilt (LLT) position to relieve inferior vena cava (IVC) compression from the gravid uterus thereby increasing venous return. However, the relationship between patient position and proximal intrahepatic IVC filling has never assessed directly. This study set out to determine the effect of LLT position on intrahepatic IVC diameter in third trimester patients under real-time visualization with ultrasound. METHODS This prospective observational study on the labor and delivery floor of a large urban academic teaching hospital enrolled patients between 30 and 42 weeks estimated gestational age from August 2011 to March 2012. Patients were placed in three different positions: supine, LLT, and right lateral tilt (RLT). After the patient was in each position for at least 3 min, IVC ultrasound using the intercostal window was performed by one of three study sonologists. Maternal and fetal hemodynamics were also monitored and recorded in each position. RESULTS A total of 26 patients were enrolled with one excluded from data analysis due to inability to obtain IVC measurements. The median IVC maximum diameter was 1.26 cm (95% confidence interval [CI] 1.13-1.55) in LLT compared to 1.13 cm (95% CI 0.89-1.41) in supine, p=0.01. When comparing each individual patients LLT to supine measurement, LLT lead to an increase in maximum IVC diameter in 76% (19/25) of patients with the average LLT measurement 29% (95% confidence interval 10-48%) larger. Six patients had the largest maximum IVC measurement in the supine position. No patients experienced any hemodynamic instability or distress during the study. CONCLUSION IVC ultrasound is feasible in late pregnancy and demonstrates an increase in diameter with LLT positioning. However, a quarter of patients had a decrease in IVC diameter with tilting and, instead, had the largest IVC diameter in the supine position suggesting that uterine compression of the IVC may not occur universally. IVC assessment at the bedside may be a useful adjunct in determining optimal positioning for resuscitation of third trimester patients.

Use of Ultrasound to Diagnose and Manage a Five-Liter Empyema in a Rural Clinic in Sierra Leone

We report the case of a dyspneic patient with a five-liter pleural empyema that was diagnosed and managed in a resource-limited clinic in a rural part of Sierra Leone. The diagnosis and management of this condition are usually guided by imaging modalities such as X-rays or CT scans. However, these resources may not be available in austere settings in developing countries. Because emergency physicians work in a variety of clinical settings, they should be well versed in the use of portable ultrasound machines to diagnose, treat, and manage many different conditions.

Effect of the Sphere Standards on the incidence of communicable and infectious diseases in a returnee camp in South Sudan

Abstract Background The Sphere Standards are primarily focused on factors that acutely affect survival instead of guiding long-term development in displaced populations and have gained consensus in more than 200 aid organisations. However, research was not available to back up every Standard and in those cases the Standards were based on expert or consensus opinion. Therefore, research to validate or refine the Standards will be of benefit to the humanitarian community and the people they serve. Methods A retrospective study was done at a UN High Commissioner for Refugees camp for returnees from Sudan to South Sudan before and after an intervention to introduce the Sphere Standards for water, sanitation, and hygiene (WASH). Data were collected from May 17, 2012, to July 31, 2012. The daily proportion of the camp diagnosed with a communicable or infectious disease was calculated by comparing the daily camp population to the daily counts from the camps medical clinic. A χ 2 analysis was done to compare the weekly disease proportions before and after the camp met the Sphere Standards for WASH. Findings The camp clinic recorded 12 655 consultations. The weekly prevalences of the camp population diagnosed with diarrhoea, an upper respiratory tract infection, or a lower respiratory tract infection in the week before the camp met the Sphere Standards were 0·67%, 0·59%, and 0·34%, respectively. 2 weeks afterwards, they were 0·99%, 1·68%, and 0·57%, respectively. In the fourth week the prevalences for all three decreased (0·82%, 1·48%, and 0·39%, respectively). This pattern was statistically significant for all age groups and also for subgroup analysis on returnees younger than 5 years. Percentages for the diseases tracked ranged from 0·14% to 1·68% with p Interpretation Factors such as the massive influx of returnees to the camp and the introduction of local pathogens into the returnee camp population probably muted the initial effects of improved WASH on the camp. These results suggest that achievement and maintainence of the Sphere Standards will have a significant, although possibly delayed, effect on the incidence of communicable and infectious diseases during a complex humanitarian emergency. Funding None.

That's Not An Abscess!

[Ann Emerg Med. 2013;62:98.] A 45-year-old woman presented to a refugee camp clinic near Juba, South Sudan, with 1 week of a painful lesion on her left thigh. She had been treated 2 days before and received a diagnosis of cellulitis. Physical examination revealed a 0.5-cm lesion draining serosanguineous fluid, with surrounding induration (Figure 1). A mobile organism was removed from the wound (Figure 2; Video E1, available online at http://www.annemergmed.com). Figure 1. A mobile, white organism observed inside the wound on the patient’s left thigh.