Association of BK viremia with human leukocyte antigen mismatches and acute rejection, but not with type of calcineurin inhibitor.

INTRODUCTION: BK viremia and polyomavirus-associated nephropathy (PVN) represent a significant problem after kidney transplantation. Both are associated with intensified immunosuppression, but other risk factors and the impact of a screening program on outcome are incompletely understood. METHODS: Here, we report on the short- and long-term outcome of a cohort of patients, who were transplanted in 2006/2007 and included in a newly introduced systematic 3-monthly screening for BK viremia at the University Hospital Zurich. In patients testing positive for BK viremia, screening frequency was intensified and immunosuppression reduced. Patients with suspected PVN underwent transplant biopsy. RESULTS: Among 152 included patients, 49 (32%) tested positive for BK viremia, but only 8 developed biopsy-proven PVN. BK viremia had a significant impact on estimated glomerular filtration rate and proteinuria in the first 2 years. Acute rejection episodes and the number of human leukocyte antigen (HLA) mismatches were the strongest independent predictors of BK viremia in a multiple logistic model. In contrast, no particular immunosuppressive agent or regimen was associated with enhanced risk. CONCLUSION: Taken together, systematic BK viremia screening led to detection of a high percentage of viremic patients. With adjustment of immunosuppression, an excellent outcome was achieved. The independent association of HLA mismatches with BK viremia suggests impaired polyomavirus immunosurveillance in highly mismatched allografts.

Stack emissions tests in a brick manufacturing Hoffmann kiln: firing of municipal solid waste.

This article reviews the results obtained from stack emissions analysis during the co-firing process of municipal solid waste (MSW) from the municipality of Tabio, Colombia, in a Hoffmann-type brick kiln. MSW (2 tonne) was incinerated and about 18.5 tonnes of clay were processed into brick using one and four kiln chambers, respectively. During the process, the following emissions were investigated: particulate emissions, emissions of SO(2), SO(3), NO( X), metals (Sb, As, Cd, Co, Sn, Cr, Cu, Mn, Ni, Hg), hydrofluoric and hydrochloric acid, hydrocarbons (such as methane) and emission of polychlorinated dioxins and furans. Also, CO emissions were monitored during each test to evaluate the influence of MSW co-firing on that parameter. The observed emissions concentrations proved to be below the threshold values issued by MAVDT, the environmental authority in Colombia, indicating that the emissions were under control during the proposed process. In addition, statistical analysis showed that the emissions were 10-40% below the regulation limit with a confidence of 95%.

Bronchial asthma: information on phytotherapy with essential fatty acids. Interactions between essential fatty acids and steroid hormones.

The pharmacological treatment of bronchial asthma is based on the inhalation of bronchodilative beta2 agonists and steroid hormones. In view of the therapeutic successes obtained with evening primrose oil in the treatment of neurodermatitis in children, the question arises whether this phytotherapeutic substitution therapy could at least partly replace symptomatic pharmacotherapy in bronchial asthma. It is shown that this will only be successful if one dispenses with the anti-inflammatory effect of the treatment with steroid hormones.

Flavonoids and tannins: plant-based antioxidants with vitamin character.

Persistent activation of the neuroendocrine stress axis is the major cause of a continuous catabolic alteration of the metabolism. This often causes an oxidative stress situation with increased release of O2 and NO radicals and pro-inflammatory cytokines. For the correction of these metabolic states, an adequate supply of plant-based antioxidants, especially flavonoids and tannins, is indicated. These are plant-based polyphenols which, like vitamins cannot be synthesized by the animal organism. Vitamin E in combination with vitamin C and beta-carotene are currently considered worldwide as the standard antioxidative therapy. However, it has recently been shown that, depending on the iron status of the recipient, pharmacological doses of these vitamins sometimes have beneficial, but often also no effect or harmful effects, so that, for a more reliable antoxidative action, adequate dietary supply of a mixture of flavonoids and tannins seems preferable.

The role of the Th-1 to Th-2 shift of the cytokine profiles of CD4 helper cells in the pathogenesis of autoimmune and hypercatabolic diseases.

The task of the immune system is the continuous elimination of endogenous cellular debris and the elimination, when necessary, of exogenous structures. It therefore seems useful and practical to add to the paradigms 'self' and 'not self' the term 'altered self'. The concept of stress, introduced by W. B. Cannon and H. Selye in the 1930s, covers the wide range of aggressive environmental influences which for their part result in a uniform shift of the metabolism in the direction of catabolism. This results from the activation of the neuroendocrine stress axis, hypothalamus-pituitary-adrenals, and causes an increased release of catecholamines and glucocorticoids. These latter substances limit life-threatening acute-phase reactions by endogenous inflammation mediators. The purpose of the shift of the cytokine profiles of the CD4 lymphocytes from Th-1 to Th-2 is, with the return of a raised cortisol level to normal values, to temporarily take over the anti-inflammatory functions of the cortisol. A sustained Th-2 shift is an expression of a persistent hypercortisolism in autoimmune states. The suppression of the anti-inflammatory effects of cortisol as a result of states of excessive stress leads to hypercatabolic diseases such as AIDS, sepsis and toxic shock syndrome and protein calorie malnutrition (NAIDS). In the prevention and treatment of AIDS and NAIDS, besides the elimination of the causes of stress, the prophylactic and therapeutic efforts are based mainly on the activation of the mesenchymal production of anabolic matrix components, mainly glycosaminoglycans, and the neutralization of O2 and NO radicals and inflammation mediators from macrophages by polyanions and polyphenols. In our opinion, in sepsis and toxic shock syndromes, lasting reduction of the mortality rates for these diseases is best achieved through the early administration of high intravenous doses of gammaglobulins.

The pathogenesis and prevention of atherosclerosis.

Most measures taken to prevent atherosclerosis still aim at lowering the cholesterol content of the plasma lipoproteins by dietary and pharmacological means. This approach has only proved successful to a limited extent. Diseases secondary to atherosclerosis are still the commonest cause of death in western industrialized countries. As all metabolic processes are regulated by opposing processes of equilibrium, i.e. by processes directed towards performance and recovery, we asked ourselves whether the fatty degeneration and sclerosis of the arteries could be causally related to a continuous dysregulation of these processes. We consider this to be the case, with a continuous deficiency of glycosaminoglycans (heparin, heparinoids) on the endothelial surface of the vessels. Numerous studies indicate that in the case of thinning of the anionic glycosaminoglycan film on the endothelial surface, the lipoprotein-lipase and antithrombin III activity induced by heparin is reduced, as result of which hyperlipoproteinaemia and increased tendency to thrombosis can only by compensated for to an inadequate extent. The formation of glycosaminoglycans is a characteristic of all mesenchymal cells, whereby the exogenous introduction of glycosaminoglycans into the extracellular space is of decisive importance for adequate glycosaminoglycan synthesis. Since Engelberg reported outstanding results obtained with heparin injections in the prevention and treatment of atherosclerotic disorders of the cardiac circulation, we considered it appropriate to use the well-proven dietary supplement of glycosaminoglycans in rheumatology, in the treatment of arthrosis, as well as in the prevention and treatment of atherosclerosis.

Stress-induced suppression of the cellular immune reactions: on the neuroendocrine control of the immune system.

Immune competence is considered as a state of equilibrium between humoral and cellular immunity. This notion fits well with the functionally antagonistic cytokine profiles in cell groups of CD4(+)-helper cells as described by Mosmann and Coffman. The Th-1 cells release mainly IL-2, IL-12 and IFN gamma and thereby stimulate the cellular immune reactions. Conversely, the Th-2 cells produce predominantly IL-4, IL-6 and IL-10, thus enhancing humoral immune reactions. Recently, it has been shown that the lymphokine profiles in Th-2 are linked to changes of the humoral balance between cortisol and dehydroepiandrosterone. These studies show that there exist states of equilibrium between T- and B-cell-mediated immune reactions, which may selectively be altered to the disadvantage of the T-cellular immunity by a stress-induced enhancement of cortisol release. In an attempt to restitute stress-induced immunosuppression, a dampening of the cortisol release hormone in the hypothalamus should, therefore, be of primary importance.

Can we find a solution to the human immunodeficiency virus/acquired immune deficiency syndrome controversy? Is acquired immune deficiency syndrome the consequence of continuous excessive stressing of the body?

The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency virus antibody negative high-risk individuals. The disease is brought under control by cellular immune reactions and the anti-human immunodeficiency virus antibody test remains negative. Apart from proof that infection with human immunodeficiency viruses has occurred, a positive result in an anti-human immunodeficiency virus-antibody test is also an indication of an independent immunosuppression state. According to the definition of the Centers of Disease Control classical acquired immune deficiency syndrome is the consequence of infection with human immunodeficiency virus in association with continuous excessive stress, such as observed in the known risk groups. At the center of the pathogenetic process is hypercortisolism-determined damage of T lymphocytes, in which insufficiency of thymus is prominent. For this reason, in our view, there are indications for shifting efforts from the prophylaxis of infection with human immunodeficiency viruses to the prophylaxis of acquired immune deficiency syndrome by reducing stress factors.

[50 years of blood transfusion services of the Swiss Red Cross]. / 50 Jahre Blutspendedienst des Schweizerischen Roten Kreuzes.

In the postwar years the Swiss Red Cross set up and developed a blood transfusion service based on strictly nonremunerated donation. It comprises the Blood Transfusion Service Central Laboratory foundation in Berne and the Swiss Red Cross Regional Blood Transfusion Centres association. The Central Laboratory's responsibilities cover provision of stable blood plasma products and transfusion equipment and the organization of extensive services in the entire field of transfusion medicine. The Regional Centres supply the country with labile cellular blood preparations. The growth of this organization over the last 50 years is described.

Immunomodulation by intravenous immunoglobulin.

In 1980, it was observed in a child with idiopathic thrombocytopenic purpura (ITP) that intravenous administration of pooled human immunoglobulin-G (IVIG) was followed by a rapid increase of the platelet count. Prompted by this finding, a pilot study and two prospective multicenter studies on children with ITP were organized. Efficacy of this new treatment for ITP was soon confirmed worldwide. In addition to the immediate effect, long-term observations following administration of IVIG suggested the occurrence of modulation of the immune response. Also, concomitant with studies on the mechanism of action of IVIG, the use of IVIG in the treatment of patients with other immune-related disorders was explored.

Intravenous immunoglobulins: pharmacological aspects and therapeutic use.

The requirements for a present-day IVIG preparation are outlined. These are mainly: fully preserved activities of the recognition and effector functions of the IgG molecule, a normal subclass distribution, and a normal half-life after infusion. The therapeutic uses of IVIG preparations are discussed as follows: Antibody substitution in cases of generalized or partial antibody deficiency in immune-compromised patients. These include the following diseases: hypogammaglobulinemia (congenital and acquired, including the neonates); drug-induced and viral immunosuppression. Antibody substitution in cases of selective antibody deficiency in otherwise immune-competent patients. These include acute cases of consumptive antibody deficiencies of the Jarisch-Herxheimer reaction type; in particular, chronic inflammations which apparently involve ineffective immune responses in which the organism is unable to build up sufficient amounts of antibodies with the required partial specificity, which is indispensable for overcoming the disease. Modulation of the immune system by Ig-Ig interactions (mainly idiotype-anti-idiotype interactions) and Ig-Fc-receptor interactions, as it is known from the RES blockade during IVIG treatment of idiopathic thrombocytopenic purpura.

Immunoglobulin in chronic inflammatory diseases.

Several case studies are presented to illustrate the success of intravenous gammaglobulin (IVIG) therapy in ulcerative colitis, Crohn's disease, chronic anterior uveitis, herpes zoster, and relapsing genital herpes simplex. Hypothetical mechanisms explain the marked improvement of the chronic disorders, with particular emphasis on substitution of specific antibodies. The recently recognized heterogeneity of the major histocompatibility complex (MHC) is explored as one possible explanation for low and high responders to particular antigens. It is suggested that various chronic inflammatory disorders result from ineffective immune responses, and that the administration of IVIG may shift the delicate balance between the pathogen and the host to favor the latter.

[A Swiss family with the red cell antigen Pk (author's transl)]. / Eline Schweizer Familie mit dem Erythrozytenantigen Pk.

The first Swiss family with the very rare bloodgroup Pk is described. It was possible to construct the family tree through 7 generations. Due to intermarriage between cousins, the 5 Pk people can be traced back to one of three ancestors. Coupling of the gene f[3], which leads to the production of the antigene Pk on erythrocytes when in homozygote condition, with an other blood group system, could not be recorded. Natural anti-P was found in all of the Pk peoples' serum. The haemolysing effect in an incompatible transfusion, probably due to anti-P, is shown in one example.