Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Learning curves in minimally invasive esophagectomy

Surgical innovation and pioneering are important for improving patient outcome, but can be associated with learning curves. Although learning curves in surgery are a recognized problem, the impact of surgical learning curves is increasing, due to increasing complexity of innovative surgical procedures, the rapid rate at which new interventions are implemented and a decrease in relative effectiveness of new interventions compared to old interventions. For minimally invasive esophagectomy(MIE), there is now robust evidence that implementation can lead to significant learning associated morbidity(morbidity during a learning curve, that could have been avoided if patients were operated by surgeons that have completed the learning curve). This article provides an overview of the evidence of the impact of learning curves after implementation of MIE. In addition, caveats for implementation and available evidence regarding factors that are important for safe implementation and safe pioneering of MIE are discussed.     

Antibiotic hypersensitivity in CF: Drug-induced life-threatening hemolytic anemia in a pediatric patient

Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.     

PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer

Introduction  

The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK.     

Strategies to reduce pulmonary complications after esophagectomy

Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.     

Warm-reactive autoantibodies in pediatric patients: clinical and serologic correlations

The significance of warm-reactive autoantibodies in pediatric patients has not been a subject of thorough evaluation. This study was undertaken to correlate the clinical and serologic features of these antibodies to identify predictors of clinical significance. Forty-two consecutive patients with serologically detectable warm-reactive autoantibodies were studied. These patients (21 male, 21 female) had a mean age of 9 years (range: 2 mo to 21 y). Primary diagnoses included autoimmune disorders (14), sickle cell disease (14), viral infection (4), idiopathic autoimmune hemolytic anemia (2), leukemia (2), and other diseases (6). Autoimmune hemolysis, as determined by clinical and laboratory findings, was documented in 24 patients (57%). Serologic studies revealed that all patients demonstrated IgG on their red cells [Direct Antiglobulin Test (DAT) reactivity range: microscopic to 3+]; 17 (40%) also demonstrated complement (DAT reactivity range: microscopic to 2+). There was a correlation between the strength of the DAT for IgG and the presence of complement on the red cells, with both being important predictors of hemolysis. These findings may be useful in predicting the clinical significance of warm-reactive autoantibodies in pediatric patients and allow for more efficient and effective follow-up care.