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Biomedical subjects

C J Wiedermann

Publications and source records attributed to C J Wiedermann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hypersensitivity reactions associated with recombinant tissue-type plasminogen activator and urokinase.

Anaphylaxis or angioedema in response to recombinant tissue-type plasminogen activator or urokinase have been reported in only a few isolated cases. Both agents are endogenous proteins and thus considered non-antigenic. Activation of fibrinolysis may per se facilitate anaphylactoid reactions by pathophysiologic pathways that are not well understood. We report a unique case, review the literature and discuss implication for the clinician. The 25-year-old patient underwent thrombolytic treatment for extensive thrombosis of pelvic and deep lower extremity veins. The patient developed protracted anaphylactoid reactions during recombinant tissue-type plasminogen activator continuous intravenous infusion. After changing treatment to urokinase, the same symptoms recurred with more severe intensity, despite corticosteroid premedication. Symptoms resolved within hours after treatment with histamine receptor blockers. This unique observation, i.e. sequential occurrence of anaphylactoid reactions during recombinant tissue plasminogen activator and urokinase treatments, adds to existing evidence for an unspecific non-antigenic pathomechanism, and for a class effect of thrombolytics. Steroids do not prevent, but histamine receptor blockers seem to be an effective treatment of this unusual complication of thrombolytic therapy.

Abdominal Pain↗
PubMed2001

Theoretical basis for the activity of thalidomide.

The revival of thalidomide began shortly after the drug was withdrawn from the market because of its teratogenic properties. Therapeutic effects of thalidomide were found accidentally in leprosy patients with erythema nodosum leprosum (ENL). Subsequent research widened the understanding of the activity of thalidomide, and with improved methodology and the augmented background knowledge of immunology it was possible to interpret the properties of thalidomide more coherently. Effects on tumour necrosis factor-alpha (TNFalpha) release play an important role in the ability of thalidomide to affect the immune system. Alteration of synthesis and release of cytokines such as interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 and interferon-gamma is involved in the complex mechanisms of thalidomide. Thalidomide targets leucocytes, endothelial cells and keratinocytes, affecting them in a different manner and at different cellular levels. Changes in the density of adhesion molecules alter leucocyte extravasation and the inflammatory response in the tissue involved. Several mechanisms for the teratogenic action of thalidomide are currently under review, but this mode of action of the drug still remains unclear and we review evidence-based hypotheses for the teratogenicity of thalidomide. Thalidomide shows significant clinical impact in several diseases such as ENL in lepromatous leprosy, chronic graft-versus-host disease, systemic lupus erythematosus, sarcoidosis, aphthous lesions in HIV infection, wasting syndrome in chronic illness, inflammatory bowel disease, multiple myeloma and some solid tumours. In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects. However, despite the promising findings of thalidomide at the molecular level, namely its anti-TNFalpha properties and its intercalation with DNA, and activity in clinical trials, there is still a great need for more intensive research.

Animals↗
PubMed2001

The role of immune activation in endotoxin-induced atherogenesis.

Some infectious agents may contribute to atherosclerosis by maintaining a heightened state of inflammatory response. Although the risk for atherosclerosis was associated with elevated plasma levels of endotoxin, it is difficult to firmly establish what place endotoxin assumes in the etiology of this disease. As the ability for endotoxin to promote disease may depend on its ability to initiate an inflammatory response, it may be controlled by additional regulatory factors. We measured plasma levels of endotoxin and serum levels of neopterin and soluble interleukin-2 receptor in a random population of 402 men and women, 50-79 years old at the 1990 baseline evaluation (Bruneck Study). End point of the prospective survey was incident (early) atherosclerosis in the carotid arteries as assessed with duplex ultrasound. Subjects with high endotoxin levels (90th percentile) in combination with low neopterin or soluble interleukin-2 receptor levels (below median) did not differ from those with low endotoxin in their risk of incident atherosclerosis. The risk associated with high endotoxin, however, was markedly elevated in subjects with high (above median) neopterin or soluble interleukin-2 receptor levels. The study provides epidemiological evidence that the atherogenic potential of endotoxemia is affected by concomitant immune activation.

Aged↗
PubMed2001

Neuropeptides and the immune system: focus on dendritic cells.

Neuropeptides are small, biologically active peptides derived from the central and peripheral nervous system. It is increasingly clear that besides their function as neurotransmitters, these peptides have an influence on almost all body functions including the immune system. Since dendritic cells are the most efficient antigen-presenting cells that stimulate naive T cells, thus promoting adaptive immunity, it is not surprising that interactions between neuropeptides and dendritic cells take place. The current review addresses several aspects of dendritic cell-related neuroimmunology and focuses on the role of neuropeptides as immunomodulators. Moreover, we present a novel concept of neuropeptide-mediated regulation of dendritic cell migration. The importance of chemokines in immunity is generally accepted. It may be that not enough attention has been paid to the possible role of nervous system-derived peptides in regulating immune reactions.

Animals↗
PubMed2000

B lymphocyte-derived IL-16 attracts dendritic cells and Th cells.

Interaction of B lymphocytes with Th cells is a fundamental step in the establishment of humoral immunity, and recent evidence suggests that direct interaction between B lymphocytes and dendritic cells (DCs) is also an important prerequisite. Factors involved in the selective recruitment of Th cells and DCs by B lymphocytes are insufficiently defined. We set out to delineate the role of IL-16, the soluble ligand of CD4, which is expressed on Th cells and DCs. B lymphocytes express IL-16 mRNA and synthesize bioactive IL-16 protein, and IL-16 is expressed in lymph node follicles in situ. B lymphocyte supernatant efficiently induces migration of CD4+ Th cells, monocyte-derived DCs, and circulating blood DCs in nitrocellulose filter-based assays. Neutralization of IL-16 bioactivity strongly inhibits this migratory response, suggesting that IL-16 might be a major chemotactic factor derived from B cells. The present data further support the idea that IL-16 might have a role in the initiation of cellular as well as humoral immunity by mediating the cellular cross-talk among T lymphocytes, B cells, and DCs, leading to recruitment of these cell types at common anatomical sites.

B-Lymphocytes↗
PubMed2000

Successful use of continuous intravenous prostacyclin in a patient with severe portopulmonary hypertension.

INTRODUCTION: Portopulmonary hypertension, defined by a mean pulmonary artery pressure > 25 mm Hg in the presence of normal pulmonary capillary wedge pressure and portal hypertension, is a known complication of end-stage liver disease that has been associated with high morbidity and mortality at the time of liver transplantation. DESIGN: Descriptive case report. PATIENT: A 32 year old male patient suffering from end-stage hepatitis C liver cirrhosis presented with severe portopulmonary hypertension. At presentation the following pulmonary hemodynamics were measured: systolic pulmonary artery pressure (PAP) 76 mm Hg, mean PAP 42 mm Hg, pulmonary vascular resistance index (PVRI) 931, pulmonary capillary wedge pressure (PCWP) 9 mm Hg, and cardiac output (CO) 4.03 l/min. INTERVENTION: After acute hemodynamic testing the patient received 8 ng/kg/min epoprostenol (prostacyclin) by continuous intravenous infusion with an infusion pump. Hemodynamic evaluation was performed monthly by transthoracic echocardiography and right heart catheterisation after 5 months. RESULTS: After 5 months of continuous therapy right heart catheterisation revealed the following hemodynamics: systolic pulmonary artery pressure (PAP) 59 mm Hg, mean PAP 32 mm Hg, pulmonary vascular resistance index (PVRI) 561, pulmonary capillary wedge pressure (PCWP) 7 mm Hg, and cardiac output (CO) 6.95 l/min. This presents a decrease in systolic pulmonary artery pressure of approximately 22%, a decrease in mean pulmonary artery pressure of approximately 30%, a decrease in pulmonary vascular resistance of approximately 40% and an increase in cardiac output of approximately 73%. Echocardiography demonstrated a decrease in estimated systolic pulmonary artery pressure of about 37% after 8 months of therapy. No complications were observed during epoprostenol therapy. CONCLUSION: In this adult patient suffering from end-stage liver disease and portopulmonary hypertension, administration of continuous intravenous epoprostenol resulted in significant reduction of pulmonary hypertension and therefore in acceptance for orthotopic liver transplantation. Utilisation of this new therapeutic strategy might be a helpful pharmacological tool for patients with portopulmonary hypertension to make them acceptable for orthotopic liver transplantation.

Adult↗
PubMed2000

Imported malaria: six cases of severe Plasmodium falciparum infection in Innsbruck, Austria, within a period of five weeks (February/March 1999)

Six patients (age, 30-76; 3 male, 3 female) with severe malaria tropica were admitted to the Department of Internal Medicine of the Innsbruck University Hospital within a time period of five weeks. All patients had recently visited classical malaria regions some days before admission: five patients the sub-Saharan Africa and one patient Thailand and Vietnam. All six patients had to be treated in the Intensive Care Unit. Three patients developed an acute respiratory distress syndrome. Two patients died of multi-organ failure. All six patients were treated with quinine and doxycycline intravenously. In one case, exchange transfusion was performed. Only two of six patients had taken prophylactic medication: one patient chloroquine and proguanil and the other mefloquine (she suffered from a severe gastroenteritis during the journey).

Acute Disease↗
PubMed2000

Dendritic cell migration in different micropore filter assays.

Dendritic cells (DC) are highly motile and have been shown to migrate in vitro or in vivo towards various chemoattractants. Micropore filter methods with polycarbonate filters are generally used in these in vitro experiments. Among others, the main drawback of these filters is their thickness, which does not allow any assessment of effects of absolute concentration compared to gradients. The aim of this study was to establish a chemotaxis assay for dendritic cells using nitrocellulose filters, which can be adapted for checkerboard studies to distinguish between chemokinesis and chemotaxis. Immature DC were generated by culture of peripheral blood mononuclear cells using granulocyte-macrophage colony-stimulating factor and interleukin-4. We tested cell migration into nitrocellulose in a Boyden microchemotaxis chamber (leading front assay) and compared this method to the commonly used polycarbonate filter technique. Dendritic cells migrated well into nitrocellulose towards gradients of formyl peptide, complement fragment 5a, and monocyte chemotactic protein-3. The nitrocellulose method appeared to be more sensitive as compared to experiments testing migration across polycarbonate filters. Subsequent checkerboard analyses confirmed chemotactic activities of formyl peptide and complement fragment 5a. However, depending on the assay system, chemotaxis in polycarbonate filters but chemokinesis in nitrocellulose filters were observed for monocyte chemotactic protein-3. Measurement of DC migration in a cellulose nitrate micropore filter assay is more sensitive than the commonly used polycarbonate method and can be adapted for checkerboard analyses.

Chemokine CCL7↗
PubMed2000

Modulation of neutrophil migration and superoxide anion release by metoprolol.

In addition to having anti-sympathotonic effects, beta-blockers are thought to have some adrenoceptor-independent properties. Such ancillary effects are described for carvedilol acting as oxygen radical scavenger and for propranolol which blocks protein kinase C and phosphatidate phosphohydrolase. The goal of our in vitro experiments was to identify ancillary effects of the widely used beta-blockers metoprolol and atenolol in neutrophils. Neutrophil chemotaxis was tested using the leading front assay in a modified Boyden microchemotaxis chamber. Respiratory burst activity was detected fluorometrically. Inhibition of protein kinase C activity was tested with purified alpha-, beta- and gamma-isoenzyme preparation. Metoprolol dose-dependently inhibited formyl peptide-stimulated neutrophil chemotaxis and formylpeptide- and phorbol myristate acetate-triggered oxygen free radical production. These actions were not affected by the competitive presence of the beta-receptor agonist, orciprenaline. Effects of metoprolol, as well as of propranolol, and the signaling enzyme blockers were strongly time dependent. Propranolol mimicked effects of staurosporine on respiratory burst, whereas the effects of metoprolol were similar to bisindolylmaleimide, a specific protein kinase C blocker. Atenolol, a hydrophilic beta-blocker, neither affected neutrophil chemotaxis nor respiratory burst. In a cell-free system, metoprolol did not interfere with the activity of the purified protein kinase C alpha-, beta- and gamma-isoenzymes. Adrenoceptor-independent inhibition of neutrophil chemotaxis and free radical production is a novel mode of action of metoprolol that may be relevant for beneficial effects ot the beta-blocker in heart failure and endothelial preconditioning.

Adrenergic beta-Antagonists↗
PubMed2000

Secretoneurin: a functional neuropeptide in health and disease.

Chromogranins belong to an evolutionarily conserved family of proteins that serve as neuropeptide pro-proteins, besides having other functions. The secretogranin-II-derived peptide secretoneurin is a 33-amino-acid polypeptide generated by proteolytic cleavage at paired dibasic sequences that exerts its effect by binding to specific receptors. Secretoneurin receptors have been kinetically and functionally characterized indicating that they are G-protein linked. Localization of secretoneurin and functional studies have helped to elucidate roles for secretoneurin, ranging from effects in the central nervous system to the modulation of the inflammatory response in the periphery. It has been shown that secretoneurin possesses biologic activities such as stimulation of dopamine release from striatal neurons and activation of monocyte migration, suggesting that the peptide may modulate both neurotransmission and inflammatory response. With an array of actions as diverse as that seen with other sensory neuropeptides, there is scope for numerous studies and therapeutic possibilities.

Animals↗
PubMed2000

Inhibition of human peripheral blood neutrophil respiratory burst by alcohol-based venipuncture site disinfection.

Ethanol inhibits the respiratory burst of neutrophils. Therefore, the effects of alcohol-based skin disinfection on oxygen metabolism in neutrophils were tested using 70% ethanol or an ethanol-isopropanol-n-propanol mixture. Neutrophil respiratory burst activity as assessed fluorometrically by oxidation of 2', 7'-dichlorofluorescein diacetate increased at 10 min after disinfection with 70% ethanol compared to the activity at 30 s. The increase was significant for triggering oxidative burst with formyl-peptide but not with phorbol myristate acetate.

1-Propanol↗
PubMed2000

Plasma-induced endothelial activation associated with incident atherosclerosis: prospective results from the Bruneck Study.

BACKGROUND: Whether systemic inflammation is an epiphenomenon of atherosclerosis or whether it is part of the atherosclerosis causal pathway requires further study. DESIGN: As part of a prospective population survey on the course and aetiology of atherosclerosis, we investigated the effects of plasma on the endothelial monolayers inducing activation for leukocyte transmigration. METHODS: An age- and sex-stratified random sample of inhabitants of Bruneck (Italy) with and without atherosclerotic disease aged 50-69 years was selected. Carotid arteries were evaluated by duplex sonography at baseline (1990). Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). Frozen plasma samples from baseline were available for a random sample of 152 men. Monolayers of endothelial cells cultured in micropore filter insets were pre-treated with plasma, then normal human neutrophils were added to the endothelial cells and subsequent transmigration through the monolayers and micropore filters was measured. RESULTS: The endothelial monolayers were activated for transmigration of leukocytes more potently by plasma from participants with carotid artery plaques than participants without it. Increased endothelial activation with plasma at baseline was associated with the development of new atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Plasma from individuals with prevalent atherosclerosis of the carotid arteries activates the endothelium for leukocyte transmigration, suggesting the presence of systemic pro-inflammatory mediators. In an epidemiological survey, follow-up data on new lesion formation after 5 years indicated that plasma-mediated endothelium activation for interaction with leukocytes precedes the development of atherosclerotic lesions.

Aged↗
PubMed2000

Neuropeptide-induced chemotaxis of eosinophils in pulmonary diseases.

Eosinophilic lung diseases include various disease entities, and the incidence of pulmonary infiltration with eosinophilia is on the rise. Because eosinophils, well known as inflammatory cells, respond to peripheral neuropeptides in vitro and in vivo, and these peptides are also present in human airway nerves, their interactions are thought to play a major role in the initiation and perpetuation of inflammatory lung diseases. This article reviews the current literature on eosinophil biology and interactions of these cells with the neuroendocrine system. Also, implications of tachykinins and other neuropeptides in eosinophilic pulmonary diseases is discussed based on recently investigated mechanisms. Eosinophils and sensory nerves most likely influence each other in a two-directional way in the pathogenesis of pulmonary diseases. Although release of sensory neuropeptides is involved in most conditions of airway hyperresponsiveness, increased bronchial resistance, and lung eosinophilia, the role of these nervous system-derived mediators in pulmonary diseases may be underestimated.

Chemotaxis, Leukocyte↗
PubMed2000

Hepatocyte growth factor plasma levels after myocardial infarction are not affected by recombinant tissue-type plasminogen-activator therapy.

Hepatocyte growth factor (HGF), a cytokine involved in tissue regeneration, angiogenesis and lateral vessel growth, is secreted as a biological-inactive, single-chain precursor named pro-HGF. In case, of tissue injury pro-HGF is proteolytically cleaved at the extracellular locus by serine proteases. Results obtained from in vitro experiments showed that urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) can cleave single-chain HGF. In this study we measured serum HGF levels in patients with acute myocardial infarction (MCI). Two groups of patients were compared. One group (n = 7) was treated with a conventional therapy and the other group (n = 7) was subjected to a thrombolytic therapy with recombinant tissue-type plasminogen activator (rtPA). Serum samples were collected at time of admission and subsequently 12-16 hours, 20-30 hours and 50-60 hours after onset of chest pain. At admission and before administration of rtPA, serum HGF levels peaked at 16.8 +/- 2.2 ng/ml in the lysed group and at 20.7 +/- 6.5 ng/ml in the non-lysed group. Levels then continuously declined, reaching lowest values 50-60 hours after onset of chest pain (3.2 +/- 1.3 ng/ml in the group treated with rtPA versus 4.4 +/- 0.9 ng/ml in the non-lysed group). No statistical significant difference could be detected between the two groups at any time. We suggest that serine proteases other than tPA are involved in HGF activation in vivo.

Acute Disease↗
PubMed1999

A role for IL-16 in the cross-talk between dendritic cells and T cells.

Dendritic cells (DCs) in the periphery capture and process Ags, migrate to lymphoid organs, and initiate immune responses in T cells. IL-16, the soluble ligand for CD4, is a potent chemoattractant for CD4+ T cells, eosinophils, and monocytes and is mainly derived from activated T cells. Because migration is a fundamental property of DCs, we asked whether IL-16 induces chemotaxis in DCs and whether DCs are a source of IL-16. DCs were generated by culture of monocytes in IL-4 and GM-CSF for 6 days and subsequently highly purified employing magnetic beads. Migration was assayed by nitrocellulose and polycarbonate filter-based assays, and distinction of chemotaxis and chemokinesis was performed by a checkerboard analysis. Messenger RNA and protein data revealed constitutive expression and release of IL-16 by day-6 DCs. Gradients of rIL-16 induced a chemotactic response of DCs. Furthermore, the chemotactic activity of DC supernatant toward DCs themselves and T cells was mainly due to IL-16, because the addition of neutralizing Abs completely abrogated the migratory response. However, after induction of maturation by the addition of TNF-alpha and PGE2 DCs, neither expressed IL-16 mRNA nor produced IL-16 protein. We conclude that IL-16 may play a role in the trafficking of DCs and may be a major chemotactic signal from DCs toward themselves and toward T cells.

Cell Communication↗
PubMed1999

Thrombolytic therapy in adult meningococcal purpura fulminans with acute renal failure and severe perfusion deficits to the extremities.

OBJECTIVE: To investigate whether systemic administration of recombinant tissue plasminogen activator would improve organ perfusion in an adult patient with fulminant meningococcal disease. DESIGN: Descriptive case report. PATIENT: A 45-year-old female with meningococcal septic shock, purpura fulminans and multiple organ failure who was treated in an eight-bed medical intensive care unit of a University hospital. INTERVENTION: In addition to standard aggressive treatment, on each of three consecutive days the patient received recombinant tissue plasminogen activator infusions at a dose of 20 mg over 4 hrs. RESULTS: Urine output was recorded before, during, and after the recombinant tissue plasminogen activator infusions. In addition, the patient's peripheral perfusion status was documented by clinical assessment. The patient showed a dramatic improvement in urine output, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator therapy. The amount of exogenous vasopressor and inotropic support required to maintain the patient's hemodynamic status also rapidly decreased. CONCLUSIONS: In this adult patient, recombinant tissue plasminogen activator therapy resulted in improved organ perfusion similar to that reported for paediatric patients. The findings indicate a need for controlled studies concerning the use of thrombolytics in severe meningococcal disease.

Acute Kidney Injury↗
PubMed1999

Septicaemia and endomyocarditis caused by Aerococcus urinae.

Aerococcus urinae, an uncommon urinary tract pathogen, was recently shown to cause septicaemia and endocarditis in a few patients in Denmark and the Netherlands. In Austria this is the first report of a fatal course of endomyocarditis by Aerococcus urinae, associated with multiple septic infarcts.

Adult↗