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Biomedical subjects

M K Kägi

Publications and source records attributed to M K Kägi.

At least 19 recordsLinked to original sources
PubMed1999

Soluble E-selectin correlates with disease activity in cyclosporin A-treated patients with atopic dermatitis.

BACKGROUND: The expression of adhesion molecules on endothelial cells regulates leukocyte migration. The level of soluble adhesion molecules which are shed into the circulation is known to reflect the degree of inflammation, and this level can therefore be used as an indicator of disease activity. The objective of this study was first to investigate the relationship between sE-selectin levels and disease activity parameters (scores of extent, severity, itch, and sleep) in atopic dermatitis (AD) patients, and second to determine the effect of therapy with an immunosuppressive drug (cyclosporin A) on sE-selectin levels. METHODS: Fourteen patients with severe AD and 41 healthy controls were studied. sE-selectin was measured by ELISA both 2 weeks before therapy with cyclosporin A and after 16 weeks of treatment. RESULTS: At baseline, the level of sE-selectin was significantly higher in patients with AD than in healthy control subjects (P<0.0001). After treatment of AD with cyclosporin A, there was a significant reduction of the sE-selectin levels (P<0.0001). In addition, changes in sE-selectin levels significantly correlated with changes in disease activity parameters such as severity (P<0.002) and extent of disease (P<0.049). CONCLUSIONS: Soluble E-selectin is a new serologic marker in AD which reflects disease activity. Therefore, soluble E-selectin may be a useful parameter in the monitoring of this disease.

Adult↗
PubMed1999

Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study.

BACKGROUND: Cyclosporin A (CsA) has been shown to be highly effective in the therapy of atopic dermatitis (AD). However, little information exists on the treatment of AD patients with Sandimmun Neoral(R) (Neoral), a microemulsion of CsA with improved pharmacokinetic properties in comparison to Sandimmun(R). OBJECTIVE: We have compared the efficacy and tolerability of Sandimmun and Neoral. METHODS: In a randomised, monocentric, double-blind, cross-over pilot study (n = 14), each formulation was administered for 8 weeks, followed by switching to the other treatment group for another 8 weeks. RESULTS: After 2 weeks of therapy, the improvement under Neoral therapy was significantly higher than with Sandimmun (disease activity p = 0.047; extent of disease p = 0.016). In contrast, after 8 weeks of therapy, both formulations yielded similar improvement in the patients' condition. CONCLUSION: While both formulations are effective and well tolerated in the treatment of severe AD, Neoral may have a faster onset of action and higher initial efficacy, which makes it an adequate replacement for Sandimmun.

Adult↗
PubMed1998

[Specific immunotherapy--past--present--future].

Specific immunotherapy or hyposensitization has been used extensively for almost 90 years as a specific treatment of IgE-mediated allergic diseases. In hayfever and allergic asthma due to house-dust mites and animal danders (especially cat) immunotherapy is highly effective and used worldwide. The term "local immunotherapy" stands for topical administration of specific IT in allergic disorders and includes local nasal, bronchial, oral and sublingual immunotherapy. Today bronchial and oral IT can not yet be recommended for clinical practice. Local nasal IT may be indicated in carefully selected adult patients with rhinitis caused by grass- and Parietaria-pollen allergy. Sublingual (swallow) IT with pollen (Grass/Parietaria) and mite extracts can be recommended in adult patients with allergic rhinitis.

Adult↗
PubMed1998

[Therapeutic management of neurodermatitis atopica].

The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

Anti-Bacterial Agents↗
PubMed1997

Anaphylactic reactions to ingested carmine (E120).

We report five cases of anaphylactic reaction to carmine (cochineal, E120) after patients drank an alcoholic beverage. By means of positive skin prick tests (SPT) and positive RAST to carmine. IgE-mediated sensitization could be established. One nonatopic patient showed also a great amount of serum IgE antibodies to the carmine acid-albumin conjugate. Due to its widespread use in the food and cosmetic industry, carmine should be tested in the allergy work-up in case of allergic reactions after a drink or a meal.

Adult↗
PubMed1996

[Visceral and neurological complications in Varicella infections of adults].

Primary varicella-zoster virus (VZV) infections in adults generally follow a more severe course than in children and are more often associated with life-threatening complications. In the years 1992 to 1995 we observed 7 immunocompetent adults with a severe course of primary VZV infection. All 7 patients presented initially with a characteristic rash. In 6 patients the diagnosis of VZV was confirmed by ELISA on material taken from the lesions, and in all of them it was confirmed by serology. The following complications were observed: pneumonia (5x), elevated liver enzymes (4x), myocarditis (1x), encephalitis (1x) and myelitis (1x). Pulmonary lesions were characterized by bilateral interstitial infiltrates on chest-x-ray and required mechanical ventilation in 2 patients. The liver enzymes were only slightly elevated and clinically not significant. Myocarditis in one case was postulated in view of elevated creatine kinase levels, ECG-repolarization changes and AV-block III which required the insertion of a transitory pacemaker. Encephalitis presented as abnormal behaviour at work followed by seizures. Myelitis was suspected due to ascending sensory motor tetraparesis and confirmed by MRI. All patients were treated with high doses of parenteral acyclovir (3 x 10 mg/kg body weight i.v. per day) for 5-12 days. 6 patients recovered completely and only the patient with myelitis has residual neurological deficits 3 months after discharge. Although we cannot exclude the possibility that supportive therapy without acyclovir would have had the same outcome, we recommend high-dose parenteral acyclovir for treatment of visceral and neurological complications in primary VZV infections in adults.

Acyclovir↗
PubMed1995

Levels of soluble ICAM-1 in atopic dermatitis. A new marker for monitoring the clinical activity?

Levels of soluble intercellular adhesion molecule-1 (sICAM-1) were measured in sera from patients with an acute exacerbation of their atopic dermatitis (AD) (n = 16) on admission to and discharge from our department of dermatology. At admission, the sICAM-1 levels in sera from patients with AD were slightly higher than those of the blood donors (n = 100) and dropped at discharge significantly (P = 0.014) after improvement of the skin conditions. Therefore, sICAM-1 may be, together with soluble interleukin-2 receptor (sIL-2), eosinophilic cationic protein (ECP), and CD14, another marker for monitoring AD.

Adult↗
PubMed1994

Human monoclonal or polyclonal antibodies recognize predominantly discontinuous epitopes on bee venom phospholipase A2.

BACKGROUND: Two hybridomas, which secrete human monoclonal antibodies of IgG4 isotype specific for the main bee venom antigen/allergen phospholipase A2, were generated. The antigenic determinants recognized by these antibodies were mapped and compared with the binding sites of murine monoclonal and human polyclonal antibodies raised against the same antigen. METHODS: Two hybridomas were developed by fusing heteromyelomas to Epstein-Barr virus immortalized B cells obtained from beekeepers. The cloned hybridomas were stable and secreted up to 40 mg/L of antibody into the culture supernatant. Phospholipase A2 specificity of the human monoclonal antibodies was confirmed by binding and inhibition ELISA and by Western blot analysis. Epitope mapping on phospholipase A2 was done with the PEPSCAN method and ELISA techniques. RESULTS: The epitopes recognized by the human monoclonal antibodies were shown to be discontinuous and did not contain the sugar residue. Similar results were obtained with polyclonal antibodies of IgG4 isotype (from beekeepers) specific for phospholipase A2, which could also inhibit the binding of the human monoclonal antibodies to phospholipase A2. In contrast, antigen binding of the human monoclonal antibodies could not be inhibited by murine monoclonal antibodies against bee venom phospholipase A2. CONCLUSIONS: The data indicate that the human monoclonal antibodies obtained are representative of a part of the polyclonal immune response to phospholipase A2 from beekeepers and may allow a more precise analysis of the humoral immune response to phospholipase A2 that is associated with protection.

Animals↗
PubMed1994

Differential cytokine profiles in peripheral blood lymphocyte supernatants and skin biopsies from patients with different forms of atopic dermatitis, psoriasis and normal individuals.

There is increasing evidence that the activation of a selected T helper cell population producing a Th2-related cytokine pattern with IL-4 and IL-5 but not IL-2 and interferon-gamma (IFN-gamma) may be involved in the pathogenesis of IgE-mediated atopic diseases and in particular of atopic dermatitis (AD). However, the existence of a 'nonatopic' (intrinsic) form of AD (NAD) with normal serum IgE levels, negative RAST tests, negative immediate type skin reactions towards environmental allergens and a negative patients and family history for IgE-mediated allergies raised the question whether this form may be explained by a different T cell activation and cytokine pattern. In the present study we compared the distribution of peripheral blood leukocyte and lymphocyte subpopulations, their activation state and cytokine production in peripheral blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD (n = 14), psoriasis (n = 6) and normal individuals (n = 13). A characteristic eosinophilia was present in AD and NAD but not in psoriasis and normal controls. The three patient groups showed significantly increased numbers of activated CD4+ and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of spontaneously released IL-2, IL-4, IL-5 and IFN-gamma from peripheral blood lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for IL-4 and IL-5 in AD patients only. Increasingly enough, patients with NAD displayed high IL-5 but low IL-4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗
PubMed1993

T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2.

Phospholipase A2 (PLA) is a biochemically fully defined glycoprotein, representing the main allergen of bee venom. We have established CD4+ T cell clones specific to PLA from subjects allergic and nonallergic to bee sting. By screening the epitope specificity of these clones with 62 synthetic overlapping dodecapeptides representing the PLA molecule, two immunogenic epitopes, PLA81-92 and PLA113-124, were identified. Additional screening, using longer peptides of up to 18 residues, revealed a third epitope at position PLA 45-62. These epitopes are recognized by specific T cell clones in association with HLA-DP and -DQ molecules, although HLA-DR-associated responses to PLA exist. Primary in vitro proliferation of unfractionated PBMC from bee sting allergic, hyposensitized, or hyperimmune subjects to PLA-derived peptides revealed the same immunogenic sites as found in the T cell clones. Among the different groups of individuals, proliferative responses to the PLA molecule and fragments thereof were generally higher in allergic patients than in nonallergic subjects. Thus, at least three linear epitopes are involved in T cell recognition of PLA, independently whether or not subjects are allergic.

Amino Acid Sequence↗
PubMed1993

Atopic dermatitis: correlation of peripheral blood T cell activation, eosinophilia and serum factors with clinical severity.

In the first part of this study peripheral blood lymphocyte subpopulations, their activation state and various serum parameters were measured in extrinsic and intrinsic atopic dermatitis (AD) patients compared to normal individuals. Beside the characteristic eosinophilia, significantly increased numbers of CD4+ T cells with increased expression of IL-2 receptors (IL-2R) and HLA-DR were noted in the AD patients. In addition, extrinsic AD patients showed increased numbers of CD23+ B cells and decreased numbers of CD16+ natural killer cells. Moreover, increased serum levels of eosinophil cationic protein (ECP) and soluble IL-2R as well as soluble factors that prolong survival of eosinophils in vitro could be demonstrated. In the second section of this study we determine how these blood immunological parameters relate to the clinical severity of the skin lesions of AD, by weekly analysis of 12 AD patients attending a high altitude clinic for 3 to 6 weeks. The patients were divided into two groups on the basis of treatment with topical steroids, but during the observation period a significant improvement in clinical status was observed in all AD patients independent of topical steroid therapy. A progressive decrease in eosinophil and activated T cell numbers, soluble IL-2R levels and serum eosinophil survival prolonging activity could be demonstrated, which closely correlated with the clinical severity of the AD.

Adolescent↗
PubMed1993

High proportion of gamma-delta T cell receptor positive T cells in bronchoalveolar lavage and peripheral blood of HIV-infected patients with Pneumocystis carinii pneumonias.

To investigate the local immunological situation in the lung of HIV-infected patients with Pneumocystis carinii pneumonias (HIV-PCP), we analyzed the proportion and the distribution of lymphocyte subpopulations and their state of activation in bronchoalveolar lavage (BAL) and peripheral blood of 21 HIV-PCP patients (CDC classification group IV) compared to 24 HIV-negative patients with interstitial lung diseases (ILD). Peripheral blood lymphocytes (PBL) and BAL cells were stained with monoclonal antibodies. Two-color cytofluorometric analysis (flow cytometry) was performed with a cytofluorograph (Epics Profile, Coulter Corp., Hialeah, Fla., USA). In BAL from HIV-PCP patients the number of CD3-positive lymphocytes was significantly increased, yet there was no difference in the number of macrophages and neutrophils when compared to patients with ILD. Quantification of lymphocyte subpopulations showed that the increased number of BAL CD3-positive lymphocytes in HIV-PCP patients was mainly due to a significantly increased number of CD8-positive T cells, while the pulmonary CD4-positive T cells were decreased both in relative and absolute numbers. As a consequence, an inverted pulmonary CD4/CD8 ratio resulted for HIV-infected patients with PCP. Analysis of in-vivo-activated T cells in BAL and peripheral blood when measured by the expression of IL-2R, HLA-DR and VLA-1 revealed increased numbers of IL-2R and HLA-DR bearing CD8-positive T cells but significantly decreased numbers of IL-2R and HLA-DR bearing CD4-positive T cells as well as a higher number of CD8/CD57 double positive T cells in HIV-infected individuals when compared to patients with ILD.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

Disulfite-induced acute intermittent urticaria with vasculitis.

Recognition of sulfite sensitivity by the practicing dermatologist has become increasingly important. A wide spectrum of anaphylactoid reactions can occur after ingestion of sulfite additives in foods and medications. We report the case of a 47-year-old man with severe acute intermittent urticaria. A placebo-controlled oral challenge test with 50 mg sodium disulfite resulted in an acute urticaria attack. A biopsy taken 5 h after the appearance of the urticaria demonstrated a leukocytoclastic vasculitis with eosinophilia. Avoiding foods and drugs containing sulfites is often difficult due to its widespread use. Therefore, the patient should be equipped with a medical emergency kit.

Angioedema↗
PubMed1993

Falafel burger anaphylaxis due to sesame seed allergy.

With the increasing demand for vegetarian food the consumption of vegetable burgers as an alternative to beef burgers has now become widespread. Since products of this kind are often not provided with a clear description of their components or ingredients, potential allergens generally cannot be identified by the consumer. Their ingestion, however, may lead to severe allergic reactions in sensitized individuals. Here we describe nine systemic allergic reactions to sesame seeds that were diagnosed at the Allergy Unit, Department of Dermatology, Zürich, Switzerland between 1978 and 1991. In 1991 alone, we registered three cases of anaphylactic reaction to falafel vegetable burgers in patients allergic to sesame seeds. A falafel is an oriental specialty consisting of a wheat flour bun filled with chickpea balls. It is served together with a white sauce containing freshly ground sesame seeds. Our cases highlight the potential danger of vegetarian food and underline the importance of a proper allergologic assessment to recognize food allergy promptly so that the patient can eliminate the causative allergen and use suitable medication in the event of a dietary indiscretion.

Adult↗
PubMed1992

Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis.

Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p = 0.0093) and in sCD14 (p = 0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p = 0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity.

Adolescent↗