The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation

In this study, we have identified a unique combinatorial effect of the chemokines KC/MIP-2 and the cytokine granulocyte colony-stimulating factor (G-CSF) with respect to the rapid mobilization of neutrophils from the bone marrow in a model of acute peritonitis. At 2 hours following an intraperitoneal injection of thioglycollate, there was a 4.5-fold increase in blood neutrophil numbers, which was inhibited 84% and 72% by prior administration of blocking mAbs against either the chemokines KC/MIP-2 or G-CSF, respectively. An intraperitoneal injection of G-CSF acted remotely to stimulate neutrophil mobilization, but did not elicit recruitment into the peritoneum. Further, in vitro G-CSF was neither chemotactic nor chemokinetic for murine neutrophils, and had no priming effect on chemotaxis stimulated by chemokines. Here, we show that, in vitro and in vivo, G-CSF induces neutrophil mobilization by disrupting their SDF-1alpha-mediated retention in the bone marrow. Using an in situ perfusion system of the mouse femoral bone marrow to directly assess mobilization, KC and G-CSF mobilized 6.8 x 10(6) and 5.4 x 10(6) neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 x 10(6) neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization.     

Geographic and ecologic distributions of the Anopheles gambiae complex predicted using a genetic algorithm

The distribution of the Anopheles gambiae complex of malaria vectors in Africa is uncertain due to under-sampling of vast regions. We use ecologic niche modeling to predict the potential distribution of three members of the complex (A. gambiae, A. arabiensis, and A. quadriannulatus) and demonstrate the statistical significance of the models. Predictions correspond well to previous estimates, but provide detail regarding spatial discontinuities in the distribution of A. gambiae s.s. that are consistent with population genetic studies. Our predictions also identify large areas of Africa where the presence of A. arabiensis is predicted, but few specimens have been obtained, suggesting under-sampling of the species. Finally, we project models developed from African distribution data for the late 1900s into the past and to South America to determine retrospectively whether the deadly 1929 introduction of A. gambiae sensu lato into Brazil was more likely that of A. gambiae sensu stricto or A. arabiensis.     

Imaging of dental infections

Emergency Radiology - Dental infections are a common presentation in the emergency department (ED). To help guide clinical management for these infections, the radiologist must be familiar with the...     

Intermittent outpatient ultrafiltration for the treatment of severe refractory congestive heart failure

BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory to conventional medical therapy, leading to recurrent rehospitalizations. We examined the impact of intermittent outpatient ultrafiltration (UF), using either peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic data in 19 consecutive patients with refractory CHF who received intermittent outpatient UF for at least 1 year between July 1998 and November 2002. The mean left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5 patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received hemofiltration. There were 6 patients with a normal left ventricular ejection fraction (45%). After UF was started, the number of patients that were considered inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the year before UF was initiated, the number of CHF hospitalizations during follow-up was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to 3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF, and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF is a safe, feasible therapy, but it needs further evaluation in carefully designed, prospective, randomized clinical trials. UF has the potential for offering another important therapeutic option for patients with severe and refractory CHF.     

Superoxide dismutase mimetics

In this review we describe the potential role(s) of superoxide in inflammatory disorders.     

Occlusion of the Modified Blalock–Taussig Shunt: Unique Methods of Treatment and Review of Catheter‐based Intervention

Objective. To report unique methods of treatment and review catheter‐based intervention for occluded modified Blalock–Taussig shunts (BTS). Methods. Case reports and articles involving children undergoing catheter‐based treatment for occluded modified BTS were reviewed. Results. Literature review detailed 38 patients in whom occluded modified BTS were treated with 39 catheter‐based interventions. Thrombolytics alone were delivered by catheter in 13 cases. Balloon angioplasty was performed in 23 cases, 5 with stent implantation. Both thrombolytic delivery and angioplasty were performed in 3 cases, 2 with stent implantation. Intervention was initially successful at re‐establishing modified BTS patency in 35/39 (90%) of cases. Patency could not be established in 2 patients who then proceeded to the operating for surgical shunt revision. Two deaths occurred during the procedures. Three cases at Emory University demonstrate uncommon or unique instances of catheter‐based intervention: (1) declotting of a shunt in a patient supported by extracorporeal membrane oxygenation (ECMO); (2) declotting of a shunt via a right axillary arterial approach; and (3) declotting of a shunt using a carotid arterial (ECMO) cannula for percutaneous access. Conclusions. The use of catheter‐based techniques for the treatment of BTS occlusion is highly successful, and potentially avoids high‐risk re‐operative intervention. ECMO can provide for a stable patient during the procedure. Hopefully, with improved technology and innovative procedures, more children in the future with BTS occlusion can be served by successful percutaneous intervention.