Split Products Research Articles

Granulocyte concentrates from a single high-yield apheresis can be split to support multiple patients

Allogeneic granulocyte transfusion has evolved into a viable therapeutic option for immunocompromised severely neutropenic leukemic patients and those with hematopoietic stem cell transplant with life-threatening bacterial and fungal infections. The collection of larger cell doses of granulocyte concentrates (GCs) has been facilitated by the stimulation of donors with granulocyte colony stimulating factor (G-CSF) and dexamethasone. The synergistic effect of G-CSF and dexamethasone has allowed the collection of larger cell doses of GCs and its use has increased steadily. This has allowed us to split the high-yield GC products and facilitated distribution of the split GC products to a second or third patient who needs GCs but lacks donors. The main objective of this article was to present our rationale for splitting GC products and how the split GC units were transfused to multiple patients. We believe that split GCs are as equally effective as unsplit GCs and that multiple patients benefit from splitting GCs.

Serum copeptin level predicts a rapid decrease of overhydration after kidney transplantation

The assessment of proper hydration status in hemodialysis patients is difficult. None of currently available markers or measures is clinically relevant. Recently, human pre-pro-vasopressin (1-164) split product [copeptin (CPP)] - a new surrogate marker of hydration status - was introduced. The aim of the study was to analyze body weight changes in the early post-transplant period in relation to serum CPP levels before kidney transplantation. Serum CPP and NT-proBNP concentrations and osmolality were measured in 130 kidney recipients directly prior to transplantation and, additionally, in 78 of them at 14th day post-transplant. Hydration status at transplantation was calculated from the difference in the patient's body weight before transplantation and at the discharge. During the post-transplant hospitalization, the average weight change was -1.6 kg, varying from 10.5 kg loss to weight gain of 5 kg. The overall weight loss was significantly related to pretransplant serum concentration of CPP (r=0.238), but not of NT-proBNP or osmolality. Patients with the lowest initial CPP level (first tertile) had smaller post-transplant weight loss. The early kidney graft function was unrelated to pretransplant CPP. Multivariate regression model revealed that variability of post-transplant weight loss is explained by the number of antihypertensive drugs used prior to transplantation [β=0.213 (0.049-0.377)] and pretransplant CPP values [β=0.233 (0.069-0.397)]. Elevated serum CPP level predicts a rapid weight loss after kidney transplantation and seems to characterize the subgroup of patients with the greatest overhydration. These results suggest the dysregulation of physiological mechanisms of CPP secretion in hemodialysis patients.

Kaposiform Lymphangiomatosis, a Newly Characterized Vascular Anomaly Presenting with Hemoptysis in an Adult Woman

Disorders of the pulmonary lymphatic system include macro- and microcystic lymphatic malformations, primary or secondary lymphangiectasias, generalized lymphatic anomalies, diffuse pulmonary lymphangiomatosis, and combinations of lymphatic and other tissue anomalies, including lymphangioleiomyomatosis (LAM). We report a case of a patient with a newly defined entity classified as kaposiform lymphangiomatosis (KLA). This 50-year-old nonsmoking Hispanic woman presented with a 20-year history of cough, hemoptysis, chyloptysis, and pleuritic chest pain. Laboratory evaluation demonstrated a low normal platelet count, elevated d-Dimer, low normal fibrinogen, and elevated fibrin split products. Chest computerized tomography imaging showed enlarged hypodense lymph nodes in the mediastinum and hila, and peribronchovascular thickening, without evidence of cystic parenchymal lesions. Magnetic resonance imaging of the chest showed cystic mediastinal lymph nodes with heterogeneously increased T2 and decreased T1 signal intensity. Fiberoptic bronchoscopy revealed hyperemic mucosa with granular appearance suggestive of a submucosal infiltrative process. Pathological specimens revealed dilated, malformed lymphatic channels within the pleura, pulmonary septa, and bronchovascular bundles, and foci of perilymphatic and intralymphatic spindle cells which reacted with the Prospero homeobox protein 1 (PROX-1) immunostain. The morphology and immunohistochemistry results were consistent with a diagnosis of KLA. This newly recognized clinical-pathological entity among intrathoracic lymphatic anomalies is distinguished from generalized lymphatic anomaly and diffuse pulmonary lymphangiomatosis in part by characteristic hematological abnormalities and hemorrhagic complications, including hemoptysis, as experienced by our patient.

Morphology Engineering of Porous Media for Enhanced Solar Fuel and Power Production

The favorable and adjustable transport properties of porous media make them suitable components in reactors used for solar energy conversion and storage processes. The directed engineering of the porous media’s morphology can significantly improve the performance of these reactors. We used a multiscale approach to characterize the changes in performance of exemplary solar fuel processing and solar power production reactors incorporating porous media as multifunctional components. The method applied uses imaging-based direct numerical simulations and digital image processing in combination with volume averaging theory to characterize the transport in porous media. Two samples with varying morphology (fibrous vs. foam) and varying size range (mm vs. μm scale), each with porosity between 0.46 and 0.84, were characterized. The obtained effective transport properties were used in continuum-scale models to quantify the performance of reactors incorporating multifunctional porous media for solar fuel processing by photoelectrochemical water splitting or power production by solar thermal processes.

Plasma Fibrin Degradation Products (Fdp ) In Patients With Pre Eclamptic Toxaemia (Pre-eclampsia)

Plasma fibrin degradation products (F.D.P.) assay measures the amount of fibrin split products in the blood. The high levels of F.D.P. in pre-eclampsia suggests that abnormal amount of degradation products are most likely due to localized lysis of fibrin in the uterine vascular compartment. The present case control study was designed to determine the relationship between plasma fibrin degradation products and pre-eclampsia. The study was carried out in the department of Biochemistry, Chittagong Medical College during the period of September 2011 to August 2012. The samples were collected from the department of Obstetrics and Gynecology, Chittagong Medical College Hospital, age from 18- 40 years. The data were collected by a structured questionnaire including age, socioeconomic condition, gravida, para, edema, blood pressure, proteinuria, history of hypertension, family history of pre-eclampsia and diabetes mellitus. Considering the cost of experiment and length of time, total 60 patients were included in this study. Among them 40 were considered as case (Blood Pressure > or = 140/90 mm of Hg and proteinuria > 0.3 gram/day) and 20 were considered as control (Blood Pressure < 140/90 mm of Hg and no proteinuria). Plasma fibrin degradation products were measured in all samples. Study showed that plasma FDP were more increased in pre-eclamptic patients than that of normal pregnancy (21.52 + 16.47 ugm/ml Vs 10.63 + 7.12 ugm/ml), P = <0.01. Result showed that percentage of raised plasma FDP is more in preeclamptic patients (100%) than that of normal pregnancy (75%), P= <0.01. Pearson's Correlation Coefficient (r) showed that there were positive correlation between blood pressure and plasma FDP (systolic blood plessure and plasma FDP, r=0.221,P=>.0.05 and diastolic blood pressure and plasma FDP, r=0.285,P=<0.05). Significantly raised level of plasma F.D.P. in pre-eclampsia help to formulate a management plan and thereby reduce the complications of this disease. JCMCTA 2013; 24 (1):9-13

Glucagon-like peptide-1 (GLP-1) and its split products GLP-1(9-37) and GLP-1(28-37) stabilize atherosclerotic lesions in apoe−/− mice

BackroundGlucagon-like peptide-1 (GLP-1) based therapies are new treatment options for patients with type 2 diabetes. Recent reports suggest vasoprotective actions of GLP-1. Similar beneficial effects might be reached by GLP-1(9-37) and the c-terminal GLP-1 split product (28-37) although both peptides do not activate the GLP-1 receptor. We therefore investigated the actions of GLP-1(7-37), GLP-1(9-37) as well as GLP-1(28-37) on vascular lesion formation in a mouse model of atherosclerosis. Methods and resultsGLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) and LacZ (control) were overexpressed for a period of 12 weeks in apoe−/− mice on high-fat diet (n = 10/group) using an adeno-associated viral vector system. Neither of the constructs changed overall lesion size. However, GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) significantly reduced plaque macrophage infiltration (GLP-1(7-37): 40.6%, GLP-1(9-37): 47.0%, GLP-1(28-37): 40.1% decrease, p < 0.05) and plaque MMP-9 expression (GLP-1(7-37): 41.6%, GLP-1(9-37): 50.2%, GLP-1(28-37): 44.0% decrease, p < 0.05) compared to LacZ in the aortic arch. Moreover, all GLP-1 constructs increased plaque collagen content (GLP-1(7-37): 49.3%, GLP-1(9-37): 86.0%, GLP-1(28-37): 81.9% increase, p < 0.05) and increased fibrous cap thickness (GLP-1(7-37): 188.0%, GLP-1(9-37): 179.9% GLP-1(28-37): 111.0% increase, p < 0.05).These effects of GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) on plaque macrophage infiltration, MMP-9 expression and plaque collagen content were confirmed in the aortic root. ConclusionGLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) reduce plaque inflammation and increase phenotypic characteristics of plaque stability in a murine model of atherosclerosis.Future studies are needed to determine whether these effects translate into improved plaque stability and less cardiovascular events in high-risk patients with type 2 diabetes.

1-Organyl-2-azasilatran-3-ones

New 1-organyl-2-azasilatran-3-ones have been synthesized via the reaction of trifunctional silanes RSiX3 (R = Et, Pr, Ph, CH2=CH, or ClCH2; X = Cl or Me2N) with N,N-bis(2-hydroxyethyl)glycinamides (HOCH2CH2)2NCH2C(O)NHR (R = H or Me) and their N′,O-trimethylsilyl derivatives. The obtained products can be hydrolyzed to give the corresponding organylsilanetriols. Lithiation of 1-methyl- and 1-phenyl-2-azasilatran-3-ones with n-butyllithium or their reduction with lithium aluminum hydride leads to the products of splitting of the atrane backbone RSiBu3 and RSiH3 (R = Me or Ph), respectively.

On split products of quaternion algebras with involution in characteristic two

The question of whether a split tensor product of quaternion algebras with involution over a field of characteristic two can be expressed as a tensor product of split quaternion algebras with involution is shown to have an affirmative answer.

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

Photoelectrochemical application of mesoporous TiO2/WO3 nanohoneycomb prepared by sol–gel method

A mesoporous TiO2/WO3 nanohoneycomb at a molar ratio of 3:1 was prepared by sol–gel method for photoelectrochemical splitting of water. In order to create a highly porous structure, the composite TiO2/WO3 with a block copolymer internal template was deposited on the substrate covered with polystyrene (PS) nanospheres. A mesoporous TiO2/WO3 composite nanohoneycomb was obtained after removing the PS spheres and copolymer by thermal treatment. It exhibited a lower band gap energy than TiO2 so that the optical absorption edge was shifted toward the visible light region. It also showed a better photoelectrochemical efficiency of water splitting and higher production of hydrogen due to lower energy gap, higher reactive surface area, and better charge separation efficiency.

Thrombin split products (prothrombin fragment 1 + 2) in urine in patients with suspected deep vein thrombosis admitted for radiological verification

IntroductionThe appearance of prothrombin fragment 1+2 (F1+2) in urine has been associated with postoperative hypercoagulability and thromboembolism. We wanted to assess if F1+2 was released in urine (uF1+2) in patients with procoagulant disorders, and if higher levels were found in patients with radiological verified deep vein thrombosis (DVT). Materials and methodsConsecutive patients were interviewed on comorbidities and medications. An unselected total cohort (n=534) and a control cohort (n=177) were analysed. A urine sample (10ml) was collected and snap frozen before levels of uF1+2 were measured with an ELISA kit. Visualisation of DVT was done with compression ultrasound, supplied with venography when feasible. All patients were followed up for 3-6months. ResultsDVT was diagnosed in 108/534 patients. Statistical significant higher uF1+2 levels were found in patients with DVT (p<0.001), in DVT positive patients with ongoing malignancy (p=0.034) and in pregnant women compared to the control cohort (p<0.001). Non-significant increased urine concentrations were found in DVT positive vs. DVT negative patients with infections and traumas. ConclusionsLevels of uF1+2 was associated with DVT both in the total cohort and in the control cohort as well as in most patients with coexisting conditions.

Fibrin nanoparticles as Possible vehicles for drug delivery

BackgroundSeveral issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem. MethodsFibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice. ResultsFNP were spherical with size ranging from 25 to 28nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-α and downregulation of IL-6 cytokines after 6h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic. ConclusionOwing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications. General significanceOur results demonstrate the safe and promising use of FNP for biomedical applications.

Clinical and Prognostic Significance of C3d and C4d Positive Immunopathology Pattern Versus C4d Positive Alone

Purpose Immunopathologic evidence of complement activation is important for the diagnosis of antibody mediated rejection. Two long-lasting complement split products are routinely assayed in biopsies, C3d & C4d. Since C4 cleavage precedes C3 cleavage in the complement cascade, detecting both C3d and C4d in tissue suggests complement activation has run to completion, whereas a C4d(+) C3d(-) pattern may indicate halting of the cascade by regulators of complement. Worse clinical outcomes in patients with C4d(+)C3d(+) staining have been reported, but not reproduced. Methods and Materials Patients with ≥3 C4d(+) biopsies and ≥3 or Results There were 95 C4d(+) patients, 24 women, mean age of 42.4 (13 months – 68 years). 66 patients were also C3d(+). Graft dysfunction, CAV, and cardiovascular mortality occurred most often in C4d(+)C3d(+) patients (p figure ). For C4d(+)C3d(+) patients, mean time to death was 48 (14-155) months and mean time to development of CAV was 50 (25-84) months. For C4d(+)C3d(-) patients, mean time to death was 46 (20-108) months and mean time to development of CAV was 106 (60-156) months. Conclusions The prognostic significance of C4d/C3d patterns in this cohort is similar to other reports. Because adverse outcomes also occurred in C4d(+)C3d(-) cases, the prognostic significance of C4d staining alone cannot be ignored. Staining for both C3d & C4d is therefore recommended.

Complement split product C4d deposition in placenta in systemic lupus erythematosus and pregnancy‐induced hypertension

Systemic lupus erythematosus (SLE) and pregnancy-induced hypertension (PIH) are related to premature delivery and intrauterine growth restriction (IUGR), and share histological findings of the placenta. Association with complement dysregulation has been reported in pregnancy for both disorders. The purpose of this study was to investigate the utility of C4d immunohistochemistry for placentas with SLE- and PIH-associated pregnancy. C4d staining was performed on paraffin-embedded tissue of placentas from 26 patients with SLE, 26 with PIH, and 25 control cases. We used the H-score with a range of 0-300 for the evaluation of C4d immunoreactivity. Placentas of SLE and PIH cases showed a higher H-score than control cases (average, SLE, 38.3 (P < 0.05); PIH, 17.8; control, 1.68), with linear staining on the membrane of syncytiotrophoblast. C4d-high groups comprised 50% (12/26) of SLE and 35% (9/26) of PIH cases, with H-scores ranging 14-270 and 15-170. C4d-high groups were significantly associated with low-placental weights and low birth weight in both SLE and PIH (P < 0.05), and lower gestational age (P < 0.05) in PIH cases. These results suggest that C4d might be utilized as a biomarker evaluating the subsequent risk for IUGR and disease control during the gestation period in these patients.

Construction of Smart Building Skins with Flow and Bend Split Products

Global energy price development causes a growing demand for energy efficient architectural building concepts. As a part of a systemic approach, smart building skins provide an option to reduce overall energy demands. In this regard, intelligent adaptivity of the building skin promotes environmental responsivity ensuring optimized energy use. Smart skins as eco-technological environments are mostly produced with serialized and prefabricated elements. Advances in serialized pre-fabrication reduce costs in relation to structural complexity of smart skin designs. Integral potentials of flow and bend split components for adaptable façade structures are projected with an exemplified foldable structure defining a cost-effective production solution for smart skins. Integrated, experimental scripting methods, jointing and mechanizing techniques are applied for this first prototype.

Frustrated Lewis pair-like splitting of aromatic C–H bonds and abstraction of halogen atoms by a cationic [(FPNP)Pt]+species

This manuscript explores new chemistry that can be related to the unobserved 14-electron [(FPNP)Pt]+ transient (FPNP = (4-F-2-(iPr2P)C6H3)2N). Its reactivity can be accessed via abstraction of triflate from (FPNP)PtOTf (1) with K[B(C6F5)4] in various solvents serving as substrates. With benzene, toluene and fluorobenzene, net heterolytic splitting of an aromatic C–H bond across the N–Pt bond is observed, without any detectable intermediates, leading to the [(FPN(H)P)Pt–Ar]+ products (Ar = Ph, 3a; Ar = C6H4Me, 3b (ortho), 3c (meta), 3d (para); Ar = o-C6H4F, 3e). The latter can be alternatively prepared by protonation of the neutral (FPNP)Pt–Ar compounds. Compounds 3a–3e do not release free arene under thermolysis at 80 °C, and compounds 3b/c/d do not interconvert under ambient temperature. With chlorobenzene and bromobenzene, the kinetic product is the κ1-Cl or κ1-Br adduct [(FPNP)Pt–Cl–Ph]+ (4) or [(FPNP)Pt–Br–Ph]+ (10). Compound 4 rearranges into a C–H splitting product [(FPN(H)P)Pt–C6H4Cl]+ (3f), while 10 slowly reacts by formal transfer of Br atom to Pt. An analogous Cl atom transfer to Pt is observed upon the reaction of 1 with K[B(C6F5)4] in dichloromethane, producing [(FPNP)PtCl][B(C6F5)4] (9a) which features an oxidized FPNP ligand framework. X-Ray diffractometry established structures of [(FPN(H)P)Pt–C6H4F-o][B(C6F5)4] (3e, disordered rotamers), [(FPN(H)P)Pt–C6H4Me][B(C6F5)4] (disordered meta- and para-isomers 3c/d), and [(FPNP)PtCl][HCB11Cl11] (9b). DFT calculations at the PBE0 and M06-L levels on the free [(FPNP)Pt]+ cation predict a relatively small (10–12 kcal mol−1) separation between the singlet and the triplet states. The relatively low triplet energy is probably related to the viability of the unexpected halogen atom abstraction reactions.

Neutralizing complement resistance improves cell-mediated killing (CDCC) of HER2 positive breast cancer cells by Trastuzumab and Pertuzumab

Event Abstract Back to Event Neutralizing complement resistance improves cell-mediated killing (CDCC) of HER2 positive breast cancer cells by Trastuzumab and Pertuzumab Srinivas Mamidi1, Simon Hoene1 and Michael Kirschfink1* 1 University of Heidelberg, Institute for Immunology, Germany The therapeutic potential of anti-cancer mAbs is hampered by the ability of malignant cells to acquire resistance to complement, primarily by the over-expression of membrane complement regulatory proteins (mCRPs) such as CD46, CD55 and CD59. Trastuzumab and Pertuzumab are anti-HER2 monoclonal antibodies approved for the treatment of HER2-positive breast cancers, which exert only minor complement-mediated cytotoxicity (CDC). Upon opsonisation of tumor cells with the C3 split product iC3b, complement receptor 3 (CD11b/CD18) on NK cells and macrophages mediates complement-dependent cellular cytotoxicity (CDCC). Here, we investigated whether treatment of HER2 positive tumor cells with trastuzumab and pertuzumab not only leads to direct destruction by CDC but also induces CDCC and if silencing of mCRPs with siRNA enhances cell-mediated cytotoxicity. Small interfering RNAs (siRNAs), which are chemically stabilized by 2´-O-methyl sugar modifications, were encapsulated in liposomes (AtuPLEX) for delivery to Her2/neu high expressing BT474 breast tumor cells to knockdown synthesis of CD46, CD55 and CD59. Upon mCRPs knock down, CDC was significantly increased when BT474 tumor cells were treated with both trastuzumab and pertuzumab. Complement-induced apoptosis and caspase activation was augmented if mCRPs were neutralized in tumor cells. Incubation of tumor cells with both antibodies also led to increased C3 deposition (opsonization), and further augmented tumor cell killing by M1 and M2 macrophages. Furthermore, incubation of mCRP neutralized BT474 cells with PBL or NK92 cells further augmented cell-mediated cytotoxicity. Thus, the combination of both trastuzumab and pertuzumab induces CDCC and neutralization of complement regulators further enhances their anti-tumor effects. Keywords: Complement resistance, siRNA, Immunotherapy, trastuzumab, Pertuzumab Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Mamidi S, Hoene S and Kirschfink M (2013). Neutralizing complement resistance improves cell-mediated killing (CDCC) of HER2 positive breast cancer cells by Trastuzumab and Pertuzumab. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00959 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Michael Kirschfink, University of Heidelberg, Institute for Immunology, Heidelberg, Germany, kirschfink@uni-hd.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Srinivas Mamidi Simon Hoene Michael Kirschfink Google Srinivas Mamidi Simon Hoene Michael Kirschfink Google Scholar Srinivas Mamidi Simon Hoene Michael Kirschfink PubMed Srinivas Mamidi Simon Hoene Michael Kirschfink Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Validation of cord blood split products prepared by an automated method

In this study, we studied whether the contents of the two compartments of automatically processed cord blood (CB) units are comparable with respect to cell counts and viability and therefore suitable for clinical therapy. CB-derived stem cells are increasingly used for allogeneic transplantation. Many centres prepare the transplants by automated methods allowing to split the product into two portions. CB was collected at different sites in Germany and transported to a single centre for processing. Before and after cryopreservation laboratory analyses were performed to compare the quality of the two CB segments. In total, 33 products were processed [mean collection volume: 18·6 ± 1·2 mL (range 15·2-20·2 mL) segment A; mean: 4·7 ± 0·3 mL (range 4·2-5·2 mL) segment B]. CD34+ cell counts, viability of CD34+ cells and many other haematological parameters showed a good comparibility between the two segments. However, lymphocyte counts and results of clonogenic assays were significantly different between the two segments of the split product. We conclude that the preparation of the cord blood unit by the automated process results in a homogenous distribution of stem and progenitor cells. However, our findings show that the clonogenic capacity differs between the two segments.

Two septic transfusion reactions presenting as transfusion-related acute lung injury from a split plateletpheresis unit

We report two simultaneous cases of Staphylococcus aureus sepsis initially consistent with and diagnosed as transfusion-related acute lung injury. The sepsis in both cases resulted from transfusion of two split products from a single contaminated plateletpheresis unit. In each case, the platelets were given along with numerous other blood products during posterior spine surgery. The discussion includes presentation, clinical course, diagnosis, and similarities between sepsis and transfusion-related acute lung injury. The cases and discussion highlight the importance of considering sepsis as part of the differential for any patient believed to have transfusion-related acute lung injury with clinical features of sepsis. Data were collected from the patients' electronic medical records and the hospital laboratory medicine database. Our cases highlight the importance of vigilant investigation in patients suspected of transfusion-related acute lung injury, as septic transfusions are easily missed and may mimic or coexist with transfusion-related acute lung injury. Sepsis should be strongly considered whenever clinical features such as hypotension, leucopenia, and fever are noted in patients with suspected transfusion-related acute lung injury. In comparison to patients receiving red blood cells or plasma, platelet transfusion recipients are at a greater risk for sepsis from a contaminated unit. Patients developing sepsis from a contaminated blood product may meet the clinical definition of transfusion-related acute lung injury. In such cases, if the clinical syndrome is attributed solely to transfusion-related acute lung injury and bacterial sepsis is not suspected, the correct diagnosis may be missed or delayed. Consequently, appropriate treatment for sepsis would also be delayed or not provided and likely result in increased morbidity and mortality.

Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion

BackgroundRevascularization of amputated extremities after prolonged ischemia is complicated by reperfusion injury. We assessed ischemia/reperfusion (I/R) injury of porcine extremities after prolonged preservation using extracorporeal circulation (ECC). MethodsForelimbs of 32 pigs were divided into four groups based on ischemia times: group I: 6 h, group II: 12 h, group III: 0 h plus replantation, and group IV: 6 h plus replantation. Limbs were perfused with autologous blood using ECC for 12 h except group II with only 5 h perfusion. Limbs from groups III and IV were heterotopically replanted with a 7-d follow-up. Contralateral limbs served as controls in all groups. Tissue, plasma, and serum were analyzed for the extent of I/R injury. ResultsNo significant differences in tissue wet/dry ratios were found within or between groups. This finding was confirmed by histology, except for an increased damage in group IV muscles compared with baseline (P = 0.016). Complement C3 deposition was only increased in group IV muscle (P = 0.031), group II nerves (P = 0.046), and group II vessels (P = 0.037). Group IV muscle and nerve tissues were the only ones with significant IgM antibody deposition (P = 0.031) at end of perfusion. Values were normal again after replantation. Reduced complement activity and elevated IL-6, IL-8, MCP-1, VEGF, PDGF-bb, bFGF, and complement split products were found during perfusion but were normal again after replantation. Staining for heparin sulfate proteoglycans and von Willebrand factor confirmed minimal activation of endothelial cells. ConclusionThe results demonstrate that prolonged limb preservation using ECC has minimal impact on I/R-induced tissue injury. Extracorporeal perfusion is a potential limb-preserving technique encouraging further studies for use in limb revascularization.