Search PubMed⌕ Search

Biomedical subjects

U Nydegger

Publications and source records attributed to U Nydegger.

At least 19 recordsLinked to original sources

Rapid detection of antibodies to immunoglobulin A molecules by using the particle gel immunoassay.

BACKGROUND AND OBJECTIVES: Antibodies to immunoglobulin A (IgA) molecules are thought to be frequently responsible for anaphylactic reactions in transfusion medicine, but practical tests for the detection of antibodies to IgA are not yet available. MATERIAL AND METHODS: Red, high-density polystyrene beads were coated with purified IgA molecules and then used to test serum samples collected from unselected healthy blood donors (n = 105) and patients with common variable immunodeficiency and/or IgA deficiency (n = 44). For testing, the standard gel-agglutination technique (ID-Micro Typing System) was employed. RESULTS: None of the normal serum samples were reactive with IgA-coated beads and samples from only 10 patients were positive (titre range 1 : 2 to 1 : 256). Only one out of all patients studied had a history of an anaphylactic reaction and this was related to the administration of Rh(D) prophylaxis (anti-D immunoglobulin). The beads did not show non-specific agglutination and could be used repeatedly for longer than 6 months. The results were reproducible in all patients tested. CONCLUSION: The new test allows a specific and rapid detection of antibodies to IgA molecules. In order to evaluate the clinical relevance of the test, analysis is required of a wider range of antibodies that produce anaphylactic reactions.

Adult↗

Short- and long-term mechanical cardiac assistance.

With the increase in high risk patients undergoing cardiac surgery and the substantial mortality among patients waiting for cardiac transplantation, the need for mechanical circulatory support is growing. Several devices are currently available, ranging from the intra-aortic balloon pump to fully implantable ventricular assist devices. Each system has its own features, and proper patient selection as well as the timing of implantation is sometimes difficult. Algorithms for stepwise management in subgroups of patients remain controversial and the concepts of weaning patients after myocardial recovery during mechanical circulatory support need further evaluation for their long-term effects. Future identification of valuable prognostic and risk factors may help in decision-making and allow for improved survival of these often very ill patients. In this report we review the concepts of mechanical circulatory support at our institution with emphasis on a detailed overview of technical features of extracorporeal life support.

Extracorporeal Membrane Oxygenation↗

The supply of blood products in 10 different systems or countries.

Countries vary greatly in their ability to produce their own blood products including albumin and IVIgG. Part of this variability depends on the supply of plasma within the country. As has been seen most recently in the UK, the quality of the plasma and its acceptability for plasma fractionation must also be considered. Therefore concerns regarding the quality of the plasma have been added to those regarding the quantity.Only a few countries are nationally self sufficient in plasma. This has a marked effect on blood product availability and therefore the ability to treat patients. Unlike most pharmaceuticals, the plasma fractionation industry must rely, for its raw products, on plasma obtained from blood donors. As such this puts it in a potentially compromised situation since neither the supply nor the quality of the raw material can be assured and both of those will vary with time. This paper reviews the processes through which blood products are made available in 10 different systems including: Canada, England, France, Italy, Norway Scotland, Sweden, Switzerland, South Africa and USA. A series of specific questions were posed and the responses received from the various coauthors and other respondents provide comparative data on blood product availability in different areas of the world.

Blood Banks↗

Biocompatibility in transfusion medicine.

The first measurable event upon interaction of artificial surfaces with blood is adsorption of proteins within seconds or minutes. At a later stage, blood cells interact with the surfaces through the initially deposited protein layer. The chemical composition of the surface is only one criterion for differential deposition of various plasma proteins, with molecular motion (polymer chain ends, loops and their flexibility), and topography (roughness, porosity) of the surface decisively influencing the interactions as well. Initially incompatible surfaces, which may be dangerous to the patient, may be rendered compatible by physicochemical surface modifications. Modern methods to estimate biocompatibility have become so sensitive that they may detect biological modifications of the blood after contact with a surface, which has no consequence for the patient. In these cases it is often difficult to decide whether a material should be classified as biocompatible or non-biocompatible. This paper discusses some methods that we have used for the study of biocompatibility of extracorporeal circuitry. It seems to us that minute signs of laboratory evidence for bioincompatibility should not preclude usage of the material in a clinical setting.

Biocompatible Materials↗

Enhanced efficacy of autologous blood donation with epoetin alfa.

In the setting of elective orthopedic surgery, epoetin alfa has been shown to facilitate autologous blood (AB) donation and reduce allogeneic blood requirements. However, the most appropriate dose and route of administration remains to be defined. A randomized, double-blind, placebo-controlled study was therefore conducted to compare the effect of different subcutaneous (s.c.) doses of epoetin alfa on hemoglobin (Hb) and endogenous erythropoietin (EPO) levels and transfusion requirements in 62 patients donating AB prior to hip surgery. Epoetin alfa (100 or 200 IU/kg s.c. on days -30, -23, -16, and -9 prior to surgery, in conjunction with oral iron supplementation) dose-dependently ameliorated the reduction in Hb levels associated with AB donation. No patient treated with epoetin alfa required allogeneic blood compared with two placebo recipients (one of whom required additional blood because of reoperation). The results of this study confirm that relatively low dosages of epoetin alfa minimize the decrease in Hb levels during AB donation and help to reduce exposure to allogeneic blood in patients scheduled for elective orthopedic surgery.

Blood Transfusion↗

[Old and current aspects of intravenous immunoglobulin therapy].

The natural variety of IgG isotype function suggests the use of IgG for therapeutic purposes. Whereas the clinical efficacy of substituting IgG through the i.m. and i.v. routes in combating infectious complications has long been known, the usefulness of i.v. IgG in comparatively high doses for the treatment of autoimmune disease states has been discovered serendipitously upon observing normalized platelet concentrates in IVIG-treated patients with immune thrombocytopenias. In such situations, a network of regulated humoral immune capacity, inherent to the large plasma pool of healthy donations, is conferred on the recipient and helps to reestablish homeostasis of deficient immune function. The indications for IVIG in diseases with abnormal immunity are rarely first choice but must be considered when conventional and cheaper options have failed. This is the case with the following diseases: idiopathic thrombocytopenic purpura, myasthenia gravis, Guillain-Barré disease, systemic lupus, rheumatoid arthritis, Evans syndrome, auto- and alloimmune cytopenias, polymyositis/dermatomyositis as well a haemorrhagic syndrome due to inhibitors against clotting factor VIII. In order to achieve synergism, a combination of IVIG with other therapeutic measures such as immunosuppressive agents, plasma exchange and/or immunosorption may be advisable. With such combinations, particularities in disease dynamics may be taken into account acceptable dosage recommendations for the treatment of autoimmune disease are not always available. The mechanisms of action of successful IVIG infusions are not yet completely understood. Those experimentally identified include: neutralization of autoimmune induction mechanisms; activity as anti-idiotypic agents; down-regulation of the Fc receptor apparatus, up-regulation of interleukin-1 receptor antagonist; deviation of complement activation to non-inflammatory targets and modulation of superantigens.

Aged↗

[Treatment of severe idiopathic cold-agglutinin diseases using interferon-alpha 2b].

Cold agglutinin disease is an immunohemolytic anemia in which the autoantibody directly agglutinates human red blood cells below body temperature, maximally at 0 to 5 degrees C. The disease is considered to occur in primary (idiopathic) or secondary forms. The secondary form is noticed in the setting of infections (e.g. Mycoplasma pneumoniae, infectious mononucleosis), or patients with lymphoproliferative disorders. Affected patients show varying clinical presentation ranging from mild to serious hemolytic anemia, episodic hemoglobinuria, acrocyanosis, or other peripheral vaso-occlusive events which are all occasioned by cold exposure. In mild chronic cold agglutinin disease preventing cold exposure usually suffices to avoid disease exacerbation. However, treatment of severe disease is difficult. Splenectomy or glucocorticoids are generally disappointing, but exceptions have been reported. Treatment with alkylating agents, as for example chlorambucil or cyclophosphamide, may be effective in some patients. However, late effects, and in particular their carcinogenic potential when used as long-term treatment, must be born in mind. We report on a 59-year-old woman with severe cold agglutinin disease who was at first treated successfully with chlorambucil and prednisone. Based on in vitro evidence, primary cold agglutinin disease can be considered as a low grade malignant lymphoproliferative disorder in which interferon-alpha has been shown to be an effective therapeutic agent, at least in forms such as hairy cell leukemia. We therefore switched therapy to interferon-alpha 2b (three million units/m2 body surface area subcutaneously three times weekly). 18 months after treatment initiation there was no remission, but improvement of clinical and laboratory signs of the disease was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Autoimmune↗

[Stem cell apheresis--experiences in children].

Stem cell apheresis, as a means to support patients during aplasia, has become an important support in the management of patients with various malignant diseases in need for heavy therapeutic regimens. Progress in this field is due, among other reasons, to better knowledge of pathophysiology in haematopoiesis and of the functioning of cytokines. Furthermore, the technical feasibility of apheresis has been improved to such an extent as to allow for collection of a stem cell-containing fraction almost in pure form. Our experience with stem cell apheresis is relatively short but includes also children between the ages of 1 and 21 years (median: 5 1/2 years). Whereas the clinical results have been published elsewhere, we here report our experience in terms of safety, using the Fresenius AS 104 machine.

Adolescent↗

[Efficacy of 2 different leukocyte filters for erythrocyte concentrates].

By leukocyte reduction in red blood cell concentrates to < 5 x 10(6) leukocytes per transfused unit, febrile non-hemolytic transfusion reaction as well as alloimmunization and transmission of certain viral diseases (CMV, HTLV-1) can be prevented. Using a Nageotte hemocytometer with a large-volume chamber, the residual leukocyte number after filtration of 40 buffy-coat free red blood cell units with the filters Pall RC100 and Sepacell R500 B1 was determined in a clinical routine setting. Both tested filters underscored the limit (< 5 x 10(6) leukocytes per unit) set by the American Association of Blood Banks. Hemoglobin loss accounted for 8.9 g (Pall RC100) versus 7.7 g (Sepacell R500 B1), which is about 15-18% of the hemoglobin content of a red blood cell concentrate.

Blood Component Removal↗

Reduction of plasma cold agglutinin titers by means of plasmapheresis to prepare a patient for coronary bypass surgery.

A 53-year-old man with abnormally elevated cold agglutinins was treated successfully by plasma exchange so that he was able to sustain coronary artery surgery and extracorporeal circulation. Two plasma exchanges, consisting in the exchange of one plasma volume with a 5% albumin solution each, were performed in our intensive care unit with careful monitoring of vital parameters. The plasma exchanges resulted in a reduction of the titer of the cold agglutinins and of the thermal amplitude as well. With the exception of postoperative bleeding requiring re-intervention, the patient was successfully operated and could be dismissed on the 16th postoperative day in good condition.

Agglutinins↗

Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors.

Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti-idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender.

Antibodies, Anti-Idiotypic↗

[Benefits and side effects of preoperative autologous blood donation in 11 heart surgery patients].

Patients scheduled for cardiac surgery are prone to adverse reactions during blood donation due to hemodynamic instability. 11 selected patients donated three units of red blood cell concentrates and three units of fresh frozen plasma (FFP) preoperatively in 11-day intervals under careful hemodynamic monitoring. 24 hours preoperatively autologous plasmapheresis (500 ml) was carried out in 10 patients at bedside. No complications were seen in any patients. The patients' mean hemoglobin concentrations were 142 +/- 11, 133 +/- 6, 128 +/- 7 and 126 +/- 7 g/l (mean +/- 1 SD) before each autologous blood donation and before the plasmapheresis respectively. No significant changes were noted in major hematological and chemical screening tests. Serum iron, iron-binding capacity and ferritin levels remained within the normal range. Due to additional perioperative blood saving methods, such as reinfusion of centrifuged oxygenator-blood (559 +/- 119 ml) and shed mediastinal blood (518 +/- 353 ml), only two patients needed additional transfusion of 1 homologous red cell unit each. On average 2.18 autologous red cell concentrates were retransfused per patient.

Blood Chemical Analysis↗

[Anti-A/B-IgM/G immune response to accidental A-O transfusion and to Toxocara canis infestation].

We have applied a sensitive and reproducible AB0-ELISA, in combination with a hemagglutination test, for the study of class- and subclass specific humoral immune response in the AB0 system upon challenge by the intravenous route (A-type blood in a 0-recipient) and by helminthic A and B blood group antigen (Toxocara canis). After accidental transfusion, peak booster concentrations of anti-A-IgG reached 411 micrograms per g total IgG, with IgG1 and IgG2 subclasses evenly distributed. With Toxocara canis immunity, anti-A/B-IgG rose to 244 and 382 micrograms/g IgG, nearly 100% over the mean value of 15 healthy blood donors; it is noteworthy that these IgG levels almost exclusively consisted of IgG1. Both observations suggest that unusual presentation of A antigen to host leads to a predominant if not exclusive IgG booster reaction.

ABO Blood-Group System↗