Over the last several years, there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as B cell-activating factor of the TNF family and a proliferation-inducing ligand have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). In this study, we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naive B cells in vitro. Monocyte-derived DCs were cultured in vitro with TLR agonists (TLR3, 4, 5, and 9) and other factors, including CD40 ligand, GM-CSF, and IL-4 as well as the neuropeptide vasoactive intestinal peptide. Under in vitro stimulation with vasoactive intestinal peptide and CD40L, IGIP mRNA expression could be up-regulated as much as 35-fold above nonstimulated samples within 12–48 h. Naive B cells cultured with exogenous recombinant human IGIP produced IgA in greater quantities than nonstimulated controls. Finally, we demonstrate that IGIP stimulation drives the production of μ-α switch circles from IgM+IgD+ naive human B cells, indicating its role as an IgA switch factor.
This study revealed that 85.3 percent of the calls referred to the blood bank physician related to physician education and the appropriateness of blood component orders. These results emphasize the need for ongoing education of medical staff in transfusion medicine issues.
In the USA, seasonal tickborne transmission of Babesia microti occurs in the Northeast and upper Midwest. A resident of Texas became infected through a red blood cell transfusion from an asymptomatic local donor who had summered in Massachusetts. The patient's infection was diagnosed by blood smear examination in January, 7 weeks post-transfusion. He died 1 week later from variceal haemorrhage complicated by haemolysis. Premortem patient specimens and archived blood from the donor unit tested positive for B. microti antibodies and DNA. Babesiosis should be included in the differential diagnosis of post-transfusion haemolytic anaemia or thrombocytopenia, regardless of the geographical region or season.
In malaria due to Plasmodium falciparum, life-threatening complications are in part related to the degree of parasitemia. Whole blood exchange and red blood cell exchange (RCE) have been used for the rapid removal of parasites from the circulation of patients with a high parasite load complicated by cerebral, pulmonary, and renal dysfunction. We have treated three 5-45-year-old patients with hyperparasitemia and end-organ dysfunction with red cell exchange by automated apheresis as an adjunct to specific anti-malarial chemotherapy. Parasitemia dropped more than 80% in all three patients immediately after the exchange, and all patients had an uneventful and full recovery. In combination with effective anti-malarial chemotherapy, apheresis RCE is a safe and rapid approach to treat complicated malaria due to P. falciparum.
Objectives
We sought to evaluate the efficacy, efficiency and physiological consequences of automated, end-point directed resuscitation systems and compare them to formula-based bolus resuscitation.
Design
Experimental human hemorrhage and resuscitation
Setting
Clinical Research Laboratory
Subjects
Healthy volunteers
Interventions
Subjects (n=7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation (BR) 2) semi-autonomous (decision-assist, DA) fluid administration and 3) fully autonomous (closed-loop, CL) resuscitation. Hemodynamic parameters, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency.
Measurements and Main Results
All approaches achieved target BP by 60 min. Following hemorrhage, the total amount of infused fluid (BR: 30ml/kg, DA: 5.6±3 ml/kg, CL: 4.2±2ml/kg, p<0.001), plasma volume, extravascular volume (BR: 17±4ml/kg, DA: 3±1ml/kg, CL: -0.3±0.3ml/kg, p<0.001), body weight and urinary output remained stable under DA and CL and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10mmHg, p<0.001) and was lower under BR than CL at 20min (BR: 57±2mmHg CL: 69±4mmHg, p=0.036). Colloid-osmotic pressure (BR: 19.3±2mmHg DA, CL: 24±0.4mmHg, p<0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration.
Conclusions
We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison to formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.
We present a case of a 20-year-old male with Wegener's Granulomatosis involving the upper respiratory tract, lungs, and kidneys. In his fourth hospital admission, the patient presented with diffuse alveolar hemorrhage and poor pulmonary function: FiO2 of 100% and PEEP of 17cm H2O on intubation. Due to a fast clinical deterioration while receiving drug therapy (cyclophosphamide and methylprednisolone), we performed nine daily 1-volume therapeutic plasma exchanges (TPE) using 5% albumin as replacement fluid. TPE resulted in a decrease in cytoplasmic anti-neutrophil cytoplasm antibodies (c-ANCA) titer from 1:1,024 to 1:16. On the ninth day of plasmapheresis, his pulmonary status was markedly improved with FiO2 of 60% and PEEP of 8 cm H2O. The patient was later extubated and discharged home in stable condition. Wegener's Granulomatosis with pulmonary hemorrhage is not included in the current guidelines for therapeutic apheresis; therefore, we report this case and, if warranted, propose this condition to be included in the guidelines.
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