bluuebunny/crossref_metadata_2025 huggingface dataset:
Fenestrated Capillaries in Mice Submesothelial Mesenteric Microvasculature
Authors: Gotloib L , Shustak A. , Jaichenko J.
Published: April 2018

This study demonstrates the existence of fenestrated capillaries in the microvascular bed of mice mesentery. The 26.6% incidence of fenestrated capillaries observed in this study is similar to that found in rabbit diaphragmatic peritoneum. Fenestral diameters are too large to be identified as the large pore of Pappenheimer's theory. They appear to be too frequent to become the predicted large pore. Peritoneal permeability should be analyzed on the basis that molecular transfer occurs through multiple ways.
Optimal Reuse of Cuprammonium Rayon Hollow-Fibre Dialyzers
Authors: Chan MK. , Lau N.
Published: April 2018

The optimal number of times a hollow-fibre cuprammonium rayon (Terumo TAF) dialyzer could be used was determined in twelve patients. Each dialyzer was reused six times. There was a highly significant decrease in neutrophil count (46.9± 6.9%, mean ± s.e.m.), platelet count (9.6± 3.8%, mean ± s.e.m.) and serum C3 concentration (10.25± 2.4%, mean ± s.e.m.) 30 minutes after the commencement of dialysis. The intensity of these changes decreased with the reuse of the dialyzers up to the fourth time. There was a small, but significant increase in serum β2-microglobulin concentrations after a 6-hour dialysis. The difference between pre- and post-dialysis serum β2-microglobulin concentrations appeared to be greater during the 5th and the 6th use (18.8% and 20.5% vs 5.0% during the first use). The clearance rates of urea and creatinine showed a trend to decrease from the fourth use onwards and the ultrafiltration coefficient was significantly reduced from the third use (8.5± 4.0 mean ± s.e.m.) onwards so that at the sixth use it was only 75.8± 4.8%, (mean ± s.e.m.) of the value at the first use. It is concluded that the optimal number of uses a cuprammonium rayon hollow-fibre dialyzer can be put to is four.
Adsorption of ß2-Microglobulin on Dialysis Membranes: Comparison of Different Dialyzers and Effects of Reuse Procedures
Authors: Goldman M. , Lagmiche M. , Dhaene M. , Amraoui Z. , Thayse C. , Vanherweghem J.-L.
Published: April 2018

In order to measure ß2-microglobulin adsorption on dialysis membranes, uremic plasma was passed through different dialyzers in a simulated hemodialysis circuit in which both plasma and dialysate compartments were organized as closed loops, the ultrafiltration pressure being adjusted to minimize water shifts. Under these conditions, comparison of the amounts of ß2-m in the plasma and dialysate compartments allowed us to calculate the binding of ß2-m to the membrane at different times of the procedure. Whereas cuprophane membrane (Gambro gf 180m, 1.8m2) did not bind ß2-m, AN69 (Filtral, 1.1 m2), high flux polysulfone (F60, 1.2m2) and modified polyamide (Polyflux 130, Gambro, 1.3m2) were found to adsorb 49 ± 8 mg (mean ± SEM), 17 ± 5 mg and 38 ± 4 mg of 82-m, respectively. These data were confirmed in trace labeling experiments with 125I-ß2-m. Adsorption was a saturable phenomenon occurring during the first 90 min of in vitro dialysis. After reuse with peracetic acid, the adsorption capacity of AN69 membrane was lowered to 20 ± 4 mg of ß2-m, contrasting with the unchanged adsorption after reuse with sodium hypochlorite. These data indicate that adsorption significantly contributes to ß2-m removal during hemodialysis with certain dialyzers and that reuse procedures may affect the propensity of dialysis membranes to bind 82-m.
Influence of Haemodialysis Membranes on the Release of Granulocyte Elastase
Authors: Irvine L. , Travers M. , Simpson K. , Lowe G.D.O. , Courtney J. M.
Published: April 2018

The advantages of multiparameter assessment in the evaluation of the blood compatibility of biomaterials underline the importance of investigating possible relevant parameters. In this respect, a study has been made of granulocyte elastase to establish the influence of haemodialysis membranes on the release of this serine proteinase. Plasma levels of granulocyte elastase were determined as a complex with its natural inhibiter α1-proteinase. This elastase - α1 proteinase (E- α1 Pi)inhibitor complex was measured by a highly sensitive enzyme-linked immunoassay. The membranes evaluated were Cuprophan (15-11, Travenol) and polysulphone (F40, Fresenius). Samples were taken from patients undergoing maintenance haemodialysis, before the start of dialysis, after 15 and 90 minutes and again at the end of dialysis (4 h). This investigation clearly demonstrates the different response of the dialysers, and on correcting for surface area, the end-dialysis level of E-α1 Pi remained significantly greater for the Cuprophan membrane. The results support the view that the release of granulocyte elastase is a relevant parameter for inclusion in membrane compatibility assessment.
The Permeability of Dialytic Membranes to Endotoxins: Clinical and Experimental Findings
Authors: Passavanti G. , Buongiorno E. , De Fino G. , Fumarola D. , Coratelli P.
Published: April 2018

This study of 20 endotoxemic patients submitted to 70 hemodialyses (HD) found a reduction of the pre-HD limulus amebocyte lysate (LAL) positivity in 50 HD (71%), without appreciable differences in terms of effectiveness between cuprophan and AN 69 membranes. To define the mechanisms responsible for the reduction in LAL positivity during HD, the membranes were used in two in vitro studies, the first of which showed that the LAL positivity of blood containing lipopolysaccharide (LPS), submitted to hemofiltration (HF) for 300 min, remained unchanged and the ultrafiltrate remained constantly LAL negative. These results suggest that the reduction in LAL positivity observed in HD in vivo, an expression of reduced endotoxemia, cannot be attributed either to the filtration of the LPS as such or to its fragmentation following blood-membrane interaction into theoretically less filtrable molecules or to mechanisms of LPS adsorption on the membrane. The in vivo reduction of LAL positivity is more likely due to removal of the filtrable endotoxin fragments already released in the body, like lipid A, the biologically active component of LPS, known to react to LAL. This hypothesis was borne out by the second in vitro study, where the LAL positivity of blood containing lipid A, treated by HF for 80 min, gradually decreased, and dialytic permeability to lipid A was confirmed by the appearance of LAL positivity in the ultrafiltrate.
Monitoring the Kinetics of Glucose Transfer across a Bioreactor Membrane with a Glucose Sensor
Authors: Velho G. , Reach G.
Published: April 2018

Bioreactors for cell culture, in which hollow fibers are sealed into a protective jacket, cells are seeded in the fibers’ outer surface and a culture medium circulates through the fibers, have been proposed as a bioartificial pancreas. We used a needle-type glucose sensor to study the kinetics of glucose transfer across the membrane of one such device. The glucose transfer was found to be dependent on the flow rate of the circulating medium, which suggests the involvement of an ultrafiltration flux across the membrane. The glucose concentration was heterogeneous within the cell compartment. This heterogeneity, and the delay in transmission of changes in glucose concentration from the circulating medium to the cell compartment, can be ascribed to the large volume of the compartment. The design of these bioreactors should therefore be modified, in order to meet the requirements of glucose transfer kinetics of a bioartificial pancreas.
The Fluid Mechanics of a Sac-Type Ventricular Assist Device
Authors: Clark C. , Jin W. , Glaser A.
Published: April 2018

Flow visualisation and velocity measurement studies have been carried out on the liquid side of a sac-type VAD. The objectives have been to identify both good (e.g. short residence times) and bad (e.g. high turbulence levels) flow characteristics. The flow was visualised using polystyrene micro-spheres illuminated with white light on selected transverse planes across the pumping chamber and its inlet and outlet connections. These results then served as a guide for velocity measurements using laser-Doppler anemometry. Flow tests were run using water or a water/glycerol mixture. Operating conditions were determined from the appropriate fluid mechanics modelling laws to ensure dynamical similarity. Initially, steady flow behaviour was investigated including the effects of removal and insertion of the tilting-disc inlet and outlet valves. In subsequent full pumping tests, using a pneumatic driver, regions of high shear, separation, and high turbulence intensity have been identified.
Micro-Pressure Sensor for Continuous Monitoring of a Ventricular Assist Device
Authors: Nitta S. , Katahira Y. , Yambe T. , Sonobe T. , Hayashi H. , Tanaka M. , Sato N. , Miura M. , Mohri H. , Esashi M.
Published: April 2018

We have been involved in the development of a clinical ventricular assist device (VAD) system. Here, we report our investigation of in vitro and in vivo stability and sensibility of pressure microsensors. The sensors were mounted in the inflow and outflow cannulae wall to measure the left atrial and aortic pressures during VAD pumping. The pressure sensitive surface of the piezoresistive effect absolute pressure sensor was coated with a thromboresistant polymer, as was the inner surface of the cannulae of the VAD.

In the in vitro and chronic animal experiments which were of more than a month duration, reliable stability and sensitivity, without any thrombus formation on the blood contacting surface of the sensors, and high sensitivity were observed. After chronic experiments, the sensitivity of sensors was reevaluated in the mock circulatory system as compared to reference values. The relationship between the output of the micro-sensors and the reference value was linear and correlated well.
Evaluation Study of Calves with Total Artificial Heart (TAH) Surviving for 218-293 Days of Pumping
Authors: Vašků J. , Vašků Jan , Dostál M. , Guba P. , Gregor Z. , Vašků A. , Urbánek P. , Nečas J. , Doležel S. , Cídl K. , Pavlíček V. , BednaříK B.
Published: April 2018

Evaluation of five longest surviving calves among a total of 54 longterm survivors, at the Brno Research Centre was performed. These calves were treated by administration of antihypertensives and partially by electrical stimulation of the right atrium to reduce central venous pressure (CVP). Treatment for CVP was effective, as compared with two groups of 5 calves each not treated in this way, and it is assumed to be an important factor for prolongation of survival. Mineralization of driving diaphragms was present in all these calves. No preventive measures of this pathologic change were performed in this group. Another complication is hemolysis, which is partly caused by immune mechanisms initiated by administration of alpha-methyl dopa and partly by mechanical destruction due to a heavily mineralized driving diaphragm. The prevention of mineralization is another important problem for future research. Other problems, concerning the survival of TAH recipients are discussed.
Model of Removal of Immunoglobulins from Plasma by Extracorporeal Immunoadsorption with Sepharose-Protein A
Authors: Davies P. A.
Published: April 2018

A mathematical model is developed which relates the time needed to perform immunoadsorption with Sepharose-Protein A to the column dimensions and choice of whether to use one or two columns. Measurements of parameters needed to apply the model, including the reaction rate constant and adsorption capacity, are reported. It is concluded that one large column can remove immunoglobulins more quickly than two smaller columns containing the same total volume of Sepharose-Protein A, but with the penalty of a greater loss of other plasma constituents. The model involves only simple computations, and can be applied to other immunoadsorbents if the dissociation constant of the complex formed by adsorption is lower than the final plasma concentration of the molecule adsorbed.
Effects of an Acidic, Lactate-Based Peritoneal Dialysis Solution and its Euhydric, Bicarbonate-Based Counterpart on Neutrophilic Intracellular pH
Authors: Zhou X.J. , Yu A.W. , Zhou F.Q. , Ryu J. , Ing T.S. , Vaziri N.D.
Published: April 2018

An exposure of human neutrophils to an acidic (pH 5.2), lactate-based incubation mixture containing a conventional, acidic, lactate-based peritoneal dialysis solution (PDS) resulted in the development of a prompt and substantial intracellular acidosis. A comparable exposure to a euhydric, bicarbonate-based incubation mixture containing a euhydric, bicarbonate-based PDS did not bring about similar changes in intracellular pH. The absence of an intracellular acidosis in the instance of the euhydric, bicarbonate-based PDS may be the reason why this solution is more biocompatible than its acidic, lactate-based counterpart.
Autologous Blood Stem Cell Collection after Chemotherapy in Patients with Sensitive and Refractory Malignancies: A Multicenter Retrospective Study
Authors: Pierelli L. , Iacone A. , Quaglietta A.M. , Nicolucci A. , Menichella G. , Panici P. Benedetti , De Laurenzi A. , De Rosa L. , Fioritoni G. , Indovina A. , Leone G. , Majolino I. , Montuoro A. , Scimé R.
Published: April 2018

A retrospective study was undertaken to assess the factors affecting the yield of peripheral blood stem cell (PBSC) collections after chemotherapy. Fifty-five patients with malignancies, observed in 4 Italian Institutions from January 1987 to June 1991 were eligible for evaluation. This series included 19 non-Hodgkin lymphoma, 11 multiple myeloma, 9 ovarian cancer, 7 Hodgkin disease, 7 acute non-lymphocytic leukemia, 1 acute lymphoblastic leukemia, 1 neuroblastoma. Five hundred and twenty two PBSC collections were performed on 55 patients after a median of 18 days after the start of chemotherapy. The yields of PBSC collections were related to the dose of cytoreductive chemotherapy exploited for PBSC mobilization and to the number of circulating white blood cells, colony forming unit granulocyte/macrophage (CFU-GM) and the percentage of monocytes at the time of collection.

Forty-eight patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant related complications.
Potentiation of GM-CSF or GCSF Induced Mobilization of Circulating Progenitor Cells by Pretreatment with IL-3 and Harvest by Apheresis
Authors: Höcker P. , Geissler K. , Kurz M. , Wagner A. , Gerhartl K.
Published: April 2018

Recombinant human colony-stimulating factors (CSFs) are increasingly used for mobilizing progenitor cells in the peripheral blood (PB). 7 patients were treated with GM-CSF or GCSF at a dose of 5μg/kg/d for 5 days and after a treatment free interval received another cycle of the same cytokine after pretreatment with IL-3. Pretreatment with 5μg/kg/d of IL-3 for 7 days did not mobilize by itself but significantly potentiated GM-CSF or GCSF induced mobilization of PB progenitor cells in all 5 patients tested. As compared to the mobilization capacity of GM-CSF or GCSF alone, 7 day IL-3 pretreatment potentiated maximum values of CFU-GM by 3.7-6.3 fold in patients receiving GM-CSF (n=2) and by 1.8-3.3 fold in patients receiving GCSF leading to a 10-23 fold increase in numbers of circulating CFU-GM by the combination IL-3/GM-CSF, and a 26-101 fold increase by IL-3/GCSF, respectively. Stem cell apheresis in patients treated with IL-3 + GCSF or GM-CSF yielded enough PB-stem cells to ensure complete engraftment after ablative chemotherapy.
Clinical Application of Growth Factors for Collection of Circulating Hematopoietic Progenitors in Breast Cancer Patients Treated with Highdose Cyclophosphamide
Authors: Ravagnani F. , Notti P. , Siena S. , Bregni M. , Zorzino L. , Di Nicola M. , Belli N. , Gianni A.M. , Pellegris G.
Published: April 2018

Seventy-seven (68 operable breast cancer with > 9 metastatic axillary nodes and 9 inflammatory breast cancer) entered this study. During hematopoietic recovery after cancer therapy with highdose cyclophosphamide (7 g/m2; HD-CTX) circulating hematopoietic progenitors were collected by leukapheresis (LK) in all patients and then cryopreserved for autologous transplantation. Following HD-CTX, 70 patients were treated with hematopoietic growth factor(s) for 14 days: 38 with rhGM-CSF (group a), 16 with rhlL-3 (group b), 11 with sequential rhlL-3 and rhGM-CSF (group c), 5 with sequential rhlL-3 and rhG-CSF (group d). Seven control patients (group e) did not receive any growth factor.

Leukaphereses, carried out over 2-4 consecutive days per patient, were started earlier in group c and in group d patients (mean day: +12 after HD-CTX). The sequential administration of rhIL-3 and rhG-CSF (group d) resulted in clearly higher yield of CFU-GM and CD34+ cells per leukapheresis (65.9x104/Kg versus 20.9x106/Kg, respectively) if compared with other groups of treatment.
Biology and Clinical Applications of Longterm Bone Marrow Cultures
Authors: Carlo-Stella C. , Mangoni L. , Rizzoli V.
Published: April 2018

A number of clonogenic assays for short-term bone marrow culture is now available for the quantitative analysis of the various hematopoietic progenitor cell classes. The short-term assays are not suitable to analyse either stem cell selfrenewal or interactions of hematopoietic progenitors with stromal cells, especially those requiring direct cell-to-cell or cell-to-matrix contact.

The technique of longterm bone marrow culture (LTBMC) allows a sustained production of myeloid cells when marrow is placed in liquid culture at relatively high cell concentration, with appropriate supplements, temperature and feeding conditions. A peculiar feature of LTBMC is that the stromal cells promote selfrenewal as well as differentiation of the stem cells, without the need to add exogenous growth factors. The LTBMC system offers an approach able to investigate not only the proliferative and differentiative events but also sustained cell production and selfrenewal of any clonogenic cell types. In the last years, the technique of LTBMC has been increasingly used by several groups to investigate hematopoietic regulation, stromal cell function and the interactions among stromal and hematopoietic cells. In the present report, the biology of LTBMC and their possible clinical applications will be reviewed.
Quantization of CD34+ Peripheral Blood Hematopoietic Progenitors for Autografting in Cancer Patients
Authors: Di Nicola M. , Siena S. , Bregni M. , Peccatori F. , Magni M. , Ravagnani F. , Zorzino L. , Bonadonna G. , Gianni A.M.
Published: April 2018

After myeloablative regimens, combined reinfusion of peripheral blood hematopoietic circulating progenitor cells (CPC) and bone marrow, yields a very rapid hematopoietic recovery. Therefore, based on the knowledge that CPC express the CD34 and CD33 differentiation antigen, we have developed a direct immunofluorescence flow cytometry assay to detect the peak of CPC in the peripheral blood of patients treated with high dose chemotherapy and growth factors. This assay, compared to CFU-GM assay, has the following advantages: 1) easy to do 2) standardized method 3) real time information on CPC number. This work illustrates the practical aspects of this assay and substantiate the widespread use of the CD34/33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation.
Peripheral Blood Cell Harvests Yield Primitive Multilineage Progenitor Cells in the CD34+/33- Fraction
Authors: Croockewit A. , Raymakers R.A. , Trilsbeek C. , Dolstra H. , Pennings A. , De Witte T.J. , Haanen C.
Published: April 2018

The presence of primitive hematopoietic progenitor cells or stem cells in peripheral blood (PBSC's) harvests was investigated in a single cell culturing assay and compared with the results obtained in aspirates of normal bone marrow. Based on the presence of CD33, rather differentiated progenitor cells (CD34+/33+) were distinguished from more primitive cells (CD34+/33-). The growth potential of CD34+/33+ and CD34+/33- cells have been studied. Single cell sorting was performed from peripheral blood harvests, obtained from three patients with multiple myeloma during hematopoietic recovery after treatment with high dose cyclophosphamide and rhu-GM-CSF. To test the effect of “stem cell recruiting factors” the cells were sorted in 96-well plates, pre-filled with liquid medium both in the presence of IL-3 + G-CSF + GM-CSF + Epo and the same growth factors supplemented with SCF+ IL-6. Addition of SCF and IL-6 to the culturing medium enhanced the plating efficiency of CD34+/33- cells considerably more than that of CD34+/33+ cells. This was observed in harvests of peripheral blood as well as in aspirates of normal bone marrow. The differences between CD34+/33+ and CD34+/33- were even more pronounced when only the large colonies (>500 cells/well) were taken into consideration. Assuming that IL-6 and SCF are “stem cell recuiting factors”, the CD34+/33- fraction contains more clonogenic cells than the CD34+/33+ fraction. In all three patients the first CD34+ cells appearing in the peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33- (>80%). At later stages when the leukocyte counts had reached higher values the CD34+/33+ cells predominated. We conclude that peripheral blood stem cell harvests contain primitive multipotential clonogenic progenitor cells (of the CD34+/33- phenotype).
CD34+ Cell Selection: Focus on Immunomagnetic Beads and Chymopapain
Authors: Silvestri F. , Banavali S. , Savignano C. , Preisler H.D. , Baccarani M.
Published: April 2018

The aim of the present study was to develop immunoadsorption techniques for purifying CD34+ cells from the peripheral blood (PB) and the bone marrow (BM). First, we compared two methods for isolating CD34+ cells from patients with acute non-lympho-cytic leukemia. Twenty-two samples (17 PB, 5 BM) were obtained from 19 patients, were density cut and, after incubation with My 10 antibody, were separated by panning or by immunomagnetic beads. Beads allowed a significantly better separation, either in terms of purification of CD34+ cells (85.5± 11.1% vs 55.7±23.8%, p= 0.003) or in terms of depletion of CD34+ cells from the negative fractions (3.9±7.6 vs 30.9±25.1%, p= 0.008). In a second study, 2 BMs from healthy subjects and 1 BM and 2 PBs from chronic myeloid leukemia patients were separated using immunomagnetic beads. The results confirmed the previous study the overall frequency of CD34+ cells in the isolated positive fractions was 85.0± 10.6% (with a recovery of 64.0±5.7%), while it was only 2.7±6.6% in the negative fractions. In particular the purity in the two normal BMs was respectively 86 and 97%. According to these results, the great majority of clonogenic cells was separated in the CD34+ fractions. Chymopapain, that was used to detach the beads from the cells, was shown to be non-toxic to the clonogenic cells.

Positive selection of CD34+ cells with immunomagnetic beads and chymopapain is a useful method for isolating almost pure progenitors from the PB and the BM for experimental use and is under investigation for clinical applications.
Umbilical Cord Blood Stem Cell Transplantation
Authors: Miniero R. , Ramenghi U. , Crescenzio N. , Perugini L. , Busca A. , Vassallo E. , Timeus F.
Published: April 2018

Human umbilical cord blood as an alternative source of hematopoietic stem cells for bone marrow reconstitution, has recently been demonstrated to yield successful HLA-matched placental blood grafts in children. It has been shown that cord blood contains sufficient progenitor cells to effect hematological reconstitution. Since then, more than 25 cord blood stem cells (CBSCs) transplants have been performed worldwide for the treatment of a variety of malignant and nonmalignant diseases. The majority of the grafts performed thus far have utilized CBSCs from HLA-identical siblings. However, much of the interest in this setting is devoted to the potential use of CBSCs for HLA-mismatched and unrelated transplants. Preliminary results suggest that allorecognition and graft-versus-host disease may be less intense in CBSCs transplants than in recipients of similarly compatible bone marrow.

This review summarizes the results and potential future applications of cord blood transplantation.
German Multicenter Studies on Plateletpheresis from Healthy Donors
Authors: Kretschmer V. , Müller N. , Godehardt E. , Borberg H. , Neumann H.J. , Weßwange T.G. ,   German Hemapheresis Study Group
Published: April 2018

It is reported on two German Multicenter Plateletpheresis Studies with the Fresenius AS 104 cell separator accompanied by a Multicenter Counting Study. 15 centers participated, a total of 1884 separations were evaluated.

It could be shown that multicenter studies help to give a more objective opinion about a cell separator and the separation protocol used if it is possible to improve the counting methods and to eliminate individual center effects by an accompanying Multicenter Counting Study. The AS 104 proved to be a good cell separator for platelet collection regarding platelet yields (3.1 x 11″ from 3.5 I citrated blood), separation efficiency (about 45%), yield prediction (SD = ≠ 15%) and leukocyte contamination (median WBC 47x106).
Applications of Extracorporeal Photochemotherapy in “Non-oncological” Diseases
Authors: Dall'Amico R. , Zulian F. , Montini G. , Andretta B. , Murer L. , Rossetti F. , Livi U. , Zacchello G. , Zacchello F.
Published: April 2018

Photopheresis (ECP) is a new therapy for oncological and autoimmune diseases consisting in the reinfusion of 3-9x 109 leukocytes, taken from the patient by leukapheresis, and treated in an extracorporeal system with 8-methoxypsoralen and ultraviolet light A. Nine patients affected by T cell immunomediated diseases (2 scleroderma, 1 chronic GVHD, 1 polyarteritis, 1 rheumatoid arthritis and 4 heart transplant patients with numerous episodes of acute rejection) were treated with ECP. Photopheresis was performed on 2 consecutive days every 3-4 weeks. All patients affected by autoimmune diseases experienced an improvement during treatment with ECP. In 2 of the 4 patients with heart transplant, rejection was reversed by photopheresis. No major side effects were observed during the treatment.

In conclusion ECP is a safe and well tolerated therapy. Although the number of patients is small, ECP seems to be an effective modality in many diseases.
Apheresis and Biocompatibility: Complement Activation
Authors: Belloni M. , Alghisi A. , Scremin L.
Published: April 2018

When blood comes into contact with plastic surfaces of extracorporeal circuits activation of different biological systems occurs, among them the complement. This will be activated mainly through the alternative pathway but also through the classical one. The activation through the latter pathway occurs when antibodies directed against polymeric materials used for the production of extracorporeal circuits or substances utilized for their sterilization are produced by the patient's immunosystem. Even if complement activation occurs almost constantly during apheretic procedures the natural inhibitory mechanisms of this system attenuate and disguise this phenomenon. Important and clinical manifestations occur in particular patients or in case of technologically more complex techniques. In apheresis the complement activation may be implicated in the relatively frequent complications such as fever and chills, hypotension, as well as in the rare but severe cases of ARDS.
In Vitro Manipulation of Peripheral Blood Progenitor Cell Collections
Authors: Carlo-Stella C. , Rizzoli V.
Published: April 2018

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used to reconstitute hematopoiesis in patients undergoing high-dose chemoradiotherapy. PBPC collections comprise a heterogeneous population containing both committed progenitors and pluripotent stem cells and can be harvested (i) in steady state, (ii) after chemotherapeutic conditioning, (iii) growth factor priming, or (iv) both. The use of PBPC has opened new therapeutic perspectives mainly related to the availability of large amounts of mobilized hematopoietic stem and progenitor cells. Extensive manipulation of the grafts, including the possibility of exploiting these cells as vehicles for gene therapy strategies, are now possible and will be reviewed.
Plasmaplateletapheresis
Authors: Zucchelli P. , Silvestri A.R.
Published: April 2018

The double-product, plasma and platelets, is the choice of the Transfusion Center of the Ospedale Maggiore in Bologna, in order to obtain a selective low-cost product taking into consideration the technical and scientific efficacy and its real applicability in our Center's routine.
Quality Assurance in Ex Vivo Progenitor Cell Manipulation
Authors: Bonfini T. , Accorsi P. , Dell'isola M. , Giancola R. , Catinella V. , D'Antonio D. , Salemme L. , Di Bartolomeo P. , Davì G. , Iacone A.
Published: April 2018

Over the past few years, hemopoietic transplant has evolved from an investigational phase to routine therapy, thus becoming a potentially curative strategy for a large variety of diseases. Several transplant situations are still outstanding and the need for ex vivo graft manipulation for different transplantation products is growing. To obtain an ideal graft, many different methods, even sophisticated manipulations, may be required. Since transplantation products play an important role in disease outcome, the assessment of graft quality to ensure standard compliance is needed. The development of a regulatory approach to these new manipulated hematopoietic products is very complex and should come under current Good Manufacturing Practices (cGMPs). Manufacturing approach to these new blood products must be urgently introduced to accounting Quality System in Transfusion Medicine. The best way to develop compliance with standards, in agreement with internationally accepted criteria, is, likely, an accreditation system in transplantation programs.
Personalized Approach to Define Transfusion Support to Surgical Patients
Authors: Mercuriali F. , Inghilleri G. , Biffi E.
Published: April 2018

Preoperative autologous blood donation (PABD) is accepted as a standard of care to reduce the risk of allogeneic blood transfusion. However, autologous blood is considered more costly than allogeneic blood. PABD can be made more cost-effective by reducing the cost of collection and by avoiding overcollection of units. When MSBOS and SOPCAB are used to identify and exclude from PABD procedures associated with low transfusion requirements, and to define the number of units to be collected, the overall AB wastage is still around 15% (ranging from 6% to 15% for different surgical procedures). To optimize the PABD program we have developed a more personalized approach to define each patient's transfusion requirement based on the predicted blood loss in mL of RBCs, calculated per surgical operation in the previous 6-12 months, along with the blood loss that the patient can tolerate. The latter depends on the baseline circulating RBC mass and the RBC mass compatible with the patient's clinical and cardiocirculatory condition. To fulfill transfusion requirements for each patient the most effective strategy can be selected according to the type and time to surgery, PABD applicability; age and clinical status of the patients taking into account what each of the different techniques can provide in terms of volume of RBCs produced or conserved.
Tackling Uncertainty in US Local Climate Adaptation Planning
Authors: Stults Missy , Larsen Larissa
Published: April 2018

Climate adaptation presents some new forms of planning uncertainty. We identified thirteen types of climate change uncertainty and grouped these into four categories. Next, we summarized eleven planning techniques, noting that only six of these techniques reflect an adapt and monitor approach that actively engages uncertainty. We then evaluated the types of uncertainty and planning techniques identified in forty-four US local climate adaptation plans. We found no communities used scenario planning or robust strategies despite the emphasis placed on these techniques in the literature.
Suppressive effects of neonatal bisphenol A on the neuroendocrine system
Authors: Ahmed RG , Walaa GH , Asmaa FS
Published: April 2018

The aim of this study was to assess the effects of neonatal bisphenol A (BPA) administration on neuroendocrine features (the thyroid–brain axis). BPA (20 or 40 µg/kg) was orally administered to juvenile male albino rats ( Rattus norvegicus) from postnatal days (PNDs) 15 to 30. Both doses resulted in lower serum thyroxine (T4), triiodothyronine (T3), and growth hormone levels and higher thyrotropin level than the control levels at PND 30. In the neonatal cerebellum and cerebrum, vacuolation, pyknosis, edema, degenerative changes, and reductions in the size and number of the cells were observed in both treated groups. Alternatively, elevations in oxidative markers (lipid peroxidation, nitric oxide, and hydrogen peroxide [H2O2]) at both dose levels were recorded at PND 30, along with decreased activities of antioxidant markers (ascorbic acid, total thiol [t-SH], glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) with respect to control levels. Thus, the BPA-induced hypothyroid state may disturb the neonatal thyroid–brain axis via production of free radicals, and this could damage the plasma membrane and cellular components, delaying cerebrum and cerebellum development.
The neurobiology of focus and distraction: The case for incorporating mindfulness into leadership
Authors: Mohapel Paul
Published: April 2018

Increasingly health leaders are experiencing greater demands and pressures, which require the need for better focus while limiting unwarranted distractions. This article offers a neurobiological explanation of how the brain focuses and becomes distracted, in order to help health leaders gain insight into their own effectiveness. Two main neural circuits are contrasted: the mind-wandering default mode circuit and the attentional central executive system. These two systems act in an antagonistic pairing, where the degree of toggling between systems is associated with the degree a person can sustain focus and filter out unwarranted distractions. Excessive multitasking appears to compromise the neural switch of these two systems, thereby diminishing our focus and concentration. In contrast, mindfulness practice is shown to have the opposite effect by enhancing the neural switch, thereby enhancing leadership focus that can lead to greater flexibility, foresight, regulation, and creativity. To conclude, leaders who are excessively distracted, such as with multitasking, may be compromising cognitive brain functioning, while engaging in mindfulness may replenish the brain and thereby enhance leaders’ ability to sustain focus and tap into higher cognitive functioning.
Color Vision Impairment Differentiates Alzheimer Dementia From Dementia With Lewy Bodies
Authors: Flanigan Patrick M. , Khosravi Mitra A. , Leverenz James B. , Tousi Babak
Published: April 2018

Objective:

Dementia with Lewy bodies (DLB) is frequently misdiagnosed for Alzheimer dementia (AD), especially in its earlier stages. We characterized color vision impairment (CVI) in patients with DLB versus patients with AD to determine its usefulness in improving accuracy of early diagnosis.

Methods:

We retrospectively reviewed charts of patients with AD, DLB, and patients with mild cognitive impairment suspected to be in the prodromal phase of DLB (pro-DLB) or prodromal phase of AD (pro-AD). All patients underwent an online 15-hue color vision arrangement test.

Results:

Fifty-two patients were included in this study with a median age of 77 years, of which 44% were female. No significant differences in gender, age, or Montreal Cognitive Assessment existed among patients with AD (n = 15), pro-AD (n = 5), pro-DLB (n = 8), and DLB (n = 24). Of the 52 patients, 4 (2 AD, 1 DLB, and 1 pro-AD) had CVI history from a young age and were excluded from final analyses. New-onset CVI prevalence differed significantly based on diagnosis: patients with pro-AD (20%), patients with AD (15%), patients with pro-DLB (38%), and patients with DLB (78%, P < .001). In a stepwise multivariate logistic regression analysis to determine factors associated with CVI, “diagnosis type” as a binary variable (DLB or pro-DLB vs AD or pro-AD) was the only variable retained in the model (odds ratio = 9.8 [95% CI: 2.3-42.1], P < .001).

Conclusions:

Color vision impairment in patients with DLB showed a prevalence similar to the core features of DLB (∼80%) and can be supportive to a diagnosis of DLB versus AD. Pending prospective confirmation of our findings, simple online color vision testing could be incorporated into multivariate diagnostic tools to possibly improve accuracy of early diagnosis of DLB.
The Use of the Newest Vital Sign Health Literacy Instrument in Adolescents With Sickle Cell Disease
Authors: Caldwell Elizabeth Perry , Carter Patricia , Becker Heather , Mackert Michael
Published: April 2018

The purpose of this article is to discuss the use of the Newest Vital Sign (NVS) health literacy instrument in adolescents with sickle cell disease. The NVS evaluates both literacy and numeracy (the ability to understand and work with numbers) as well as the ability to locate and apply information. It is important to validate the NVS for use in adolescents, as the only currently validated instrument, the Rapid Estimate of Adolescent Literacy in Medicine–Teen (REALM-Teen), does not measure numeracy or the ability to locate or apply information. This cross-sectional, descriptive, exploratory correlational study included appraisal of data from completion of the REALM-Teen and NVS instruments by a convenience sample of 75 adolescents with sickle cell disease. The mean age of this study sample was 14.7 years ( SD = 2.2). The mean grade level of participants was 8.7 ( SD = 2.2). Internal consistency for the NVS in this population was acceptable (α = .63). Criterion validity was based on correlations between raw scores on the NVS and raw scores on the REALM-Teen. There was a significant moderate, positive correlation between NVS and REALM-Teen scores ( r = .38, p < .01), demonstrating good criterion validity. Preliminary evidence for reliability and validity of the NVS in this population was established.
The Balloon-Gas Procedure: A Technique for Repair of Retinal Detachments Requiring Large Volumes of Gas
Authors: Kreissig I. , Kamel H.
Published: April 2018

This report describes the balloon-gas procedure, a technique for obtaining large volumes of intraocular gas.

With the balloon-gas procedure a kind of “external fluid-gas exchange” allows for the safe injection of up to 1.0 ml of gas without previous pars plana vitrectomy or surgical drainage of subretinal fluid. From April 1985 to October 1988, in Tübingen, this procedure was utilized in 36 retinal detachments with breaks not suited for scleral buckling: giant tears (nine eyes), large dialyses (seven eyes), posterior breaks (16 eyes), and multiple breaks at different latitudes (four eyes). Follow-up ranged from six to 28 months (average 16 months).

Initial retinal reattachment was achieved in 28 eyes (77.8%). Reasons for initial failure were proliferative vitreoretinopathy in six eyes, and a missed break in two. Redetachment occurred in three eyes. All 11 failures were reoperated using segmental sponges (eight eyes) and gas injection (three eyes). Final reattachment was achieved in 29 of the 36 eyes (80.6%), and final failure was due to proliferative vitreoretinopathy in all seven detachments.
Proton Beam Irradiation for Treatment of Experimental Human Retinoblastoma
Authors: Svitra P. P. , Budenz D. , Albert D.M. , Koehler A.M. , Gragoudas E.
Published: April 2018

Proton beam irradiation was used to treat human retinoblastoma (Y-79 cell line) grown subcutaneously in the athymic “nude” mouse. Thirty-four tumors were included in the experimental groups, of which twenty-three were irradiated and eleven served as controls. Tumors were irradiated with protons produced at the 160 megavolts Harvard cyclotron. The dose delivered to the tumor ranged from 7.5 to 27.5 proton gray in a single treatment, and 25.0 proton gray delivered in two fractions separated by 24 hours. Reduction of tumor growth was significantly greater than controls (p<0.001) with treatment doses greater than or equal to 17.5 proton gray. Histologic examination revealed a marked decrease of mitotic activity in all specimens examined 48 hours after treatment at these higher doses. Total regression without evidence of remaining malignant cells was noted in three tumors treated at 17.5 proton gray or above. Our results indicate that human retinoblastoma in a murine host, with a tumor mass similar to that seen in a clinical setting, is sensitive to radiation by high energy protons.
Long-term follow-up Study of Nonsenile Detachment of the Retinal Pigment Epithelium
Authors: Laatikainen L. , Hoffren M.
Published: April 2018

Re-assessment of a series of fluorescein angiograms of 76 patients referred to our hospital for central serous retinopathy (CSR) between 1973 and 1982 revealed 10 eyes of 8 patients (7 males, 1 female) aged 50 years or younger (mean age 42.6 years, median 43.5, range 36-49) with serous detachment of the retinal pigment epithelium (PED) with (3 eyes) or without (7 eyes) detachment of the neuroretina. Two eyes had two discrete PEDs and two eyes showed minor pigmentary disturbance outside the PED. In the remaining six eyes no other pigment epithelial (PE) changes were observed. In five patients no PE changes were found in the fellow eye. During the follow-up period of 2.8 to 14.3 years (mean 7.3, median 6.4) three eyes had one recurrence of symptoms. The long-term prognosis was good. None of the eyes developed subretinal neovascularization or geographic atrophy, in eight eyes PED flattened with a mild degree of pigment dispersion at the site, two eyes had persistent shallow PED. The latest visual acuity was 1.0 or better in nine eyes, and 0.6 in one. It is concluded that no treatment of nonsenile PED seems to be warranted.
Retinal Ischaemia and Relative Afferent Pupil Defects in Central Retinal Vein Occlusion
Authors: Grey R.H.B. , Bloom P.A.
Published: April 2018

A consecutive series of 40 patients were assessed for relative afferent pupil defects and retinal ischaemia by fluorescein angiography.

A strong correlation was found between density of afferent defect and area of retinal non-perfusion. There was an increasing incidence of rubeosis iridis with more severe grades of afferent defects or ischaemia.
Fluorescein Angiography - Is it Safe to use in a Pregnant Patient?
Authors: Olk R.J. , Halperin L.S. , Soubrane G. , Coscas G.
Published: April 2018

We sent questionnaires to 424 retina specialists in order to compile information on the use of fluorescein angiography in pregnant women. Four-hundred and three specialists responded. Of these, 313 (78%) had never performed fluorescein angiography on a pregnant woman. Ninety specialists (22%) had performed at least one fluorescein angiogram on a pregnant woman; detailed information was obtained on 105 patients. Authors of previous reports that included fluorescein angiography during pregnancy provided information on an additional 11 patients. Substantiated side effects were nausea and/or vomiting in seven patients. Anomalies at birth, an undescended testicle and syndactyly, were reported in two children. There was one stillbirth with pathologic findings classic for toxemia and one fetal death not related in time to fluorescein angiography. One therapeutic abortion was performed for complications in toxemia. One spontaneous abortion occurred 3 days after fluorescein angiography in a patient who was four weeks pregnant. Eight children born to toxemic mothers had low birth weights. Based on our data, we conclude that fluorescein angiography does not offer a high rate of birth anomalies or complications during pregnancy.
Idiopathic Sclerochoroidal Calcification: New Observations
Authors: Munier F. , Zografos L. , Schnyder P.
Published: April 2018

Two cases of idiopathic sclerochoroidal calcification are reported with follow-up of two and ten years. In addition we have reviewed 102 cases of choroidal osteoma, including six misleading case reports which actually described idiopathic sclerochoroidal calcification and not choroidal osteoma. Clinical manifestation and the angiographic features of idiopathic sclerochoroidal calcification are outlined. The “differential diagnosis of intraocular deposition of calcium salts is discussed in detail.
Hypertensive Gas Technique for Enucleation of Choroidal Melanomas: A Preliminary Report
Authors: Kreissig I. , Jost B.
Published: April 2018

The hypertensive gas technique induces avascularity within the eye during enucleation of a melanoma. Before touching the eye for enucleation, pressure is raised to maximum by an intravitreal injection of approximately 1.4 ml of gas (perfluorocarbon, air) resulting in a rock-hard eye. Avascularity persists for the duration of enucleation. From 9/1987 to 6/1989, 15 patients with choroidal melanomas were enrolled in a prospective study with the hypertensive gas technique instead of prior radiotherapy (the death rate in that series was five out of 26 melanoma patients at three years). Inclusion criteria for the hypertensive gas technique study were the same as for our previous irradiation series: (1) absence of detectable metastases and (2) a choroidal melanoma too large for a radioactive plaque. The average base diameter of melanomas measured 13.2 mm, height 8.4 mm. The cytology was: 11x spindle, 3x mixed, 1x epithelioid cells. At re-examination in 7/1991 (average follow-up 33 months) two diabetics had died with no detectable metastases prior to death, and one of the 15 melanoma patients had died with metastases 24 months after enucleation. So far the hypertensive gas technique for enucleation of a melanoma eye seems to have no adverse effect on survival. It seems to be a simple alternative to the precautions taken otherwise and it facilitates enucleation with pratically no bleeding from the globe.
Repeated Melting of Corneal Grafts in a Patient with Rheumatoid Arthritis and Sjögren's Syndrome
Authors: Petroutsos G. , Drosos A. , Psilas K.
Published: April 2018

We present a case of corneal melting in a patient with severe rheumatoid arthritis and Sjögren's syndrome. The melting appeared in the area of a bacterial corneal ulcer that healed after treatment with antibiotics. No signs of scleritis were present. Repeated melting of two corneal grafts was seen after surgery.
Clinical Evaluation of Indocyanine Green Video-Angiography in the Diagnosis of Choroidal Neovascular Membrane Associated with Age-Related Macular Degeneration
Authors: Yuzawa M. , Kawamura A. , Matsui M.
Published: April 2018

The Authors compared ICG video-angiographic findings in 85 eyes of 78 cases of presumed choroidal neovascular membrane (CNM) associated with age-related macular degeneration with those diagnosed by fluorescein angiography. The detection rate of CNM was 68% with indocyanine green (ICG) video-angiography and 59% with fluorescein angiography. ICG video-angiography can be especially useful for identifying hemorrhagic or exudative detachments of the retinal pigment epithelium. In these cases, detection of CNM by ICG video-angiography was generally far superior to that by fluorescein angiography. However, some CNM in which leakage was identified with fluorescein angiography could not be visualized by ICG video-angiography.