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  • 1
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3–4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long-term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non-respiratory infections) are rare.Methods:  All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre-IVIG replacement period, a low-dose (200 mg/kg every 3 weeks) and a standard-dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively.Results:  Seven patients followed up for a total of 116 patient-years over the three defined periods of observation were recruited. When compared with low-dose therapy, standard-dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non-respiratory and upper respiratory infections were, in comparison, resistant to therapy.Conclusions:  Overall, these data support the use of standard-dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5–7 g/l, but underlines that some categories of infectious events (non-respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance.Objective To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323–339 (OVAp).Methods BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis.Results Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4+ T cells in BLN of OVA-treated mice only.Conclusion INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4+ T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down-regulate the IgE response.Objective To monitor the long-term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis.Methods CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase.Results Low-dose immunization with PLA2 (0.1 µg) favoured a long-term, specific T helper (Th)2 response with high IgE and IL-4 production in contrast to high-dose PLA2 (10 µg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL-4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2, which was also dose-dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen-specific, it could be induced in the high- and low-dose immunization groups, and was not solely dependent on IgE levels.Conclusion Though low-dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model-based data.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Venom immunotherapy is definitely indicated in severe systemic anaphylactic reactions to bee stings. but is not devoided of risks of anaphylaxis. Safer methods of Immunotherapy need to be developed.Objective To delineate phospholipase A2 Tcell epitopes using shoti I5mer vs long 40–60mer overlapping peptides, and to approach the potential interest of a venom immunotherapy based on the use of long peptides (1–60. 51–99. 90–134) mapping the whole phospholipase A2 molecule vs a restricted number of immunodominant epitopes.Methods Proliferation of a CD8+ T cell depleted peripheral blood mononuclear cell fraction and short-term T-cell lines from unselected bee venom hypersensitive patients in response to phospholipase A2 synthetic peptides.Results Whereas T-cell proliferation to 15mer overlapping peptides was weak, T-cell response to long overlapping peptides was in contrast vigorous in all patients, mostly directed to C-terminal peptide 90–134. Our results did not support the concept of rare dominant T-cell epitopes. and disclosed T-cell responses to multiple epitopes in several patients. No significant IgE-binding to long overlapping peptides was detected except in one patient against peptide 90–134.Conclusion 15mer peptides might not be sensitive enough to fully delineate all potential T-cell epitopes scattered along the allergen. Since they do not bind IgE in vitro or only weakly, and taking into account a T-cell response frequently directed to multipie epitopes, long overlapping peptides may represent ideal tools for immunotherapy.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 33 (1995), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: The objective was to validate acoustic rhinometry (AR) in a nasal challenge with allergen. Methods: Nasal response to allergen provocation was based on clinical and symptom scores, cross-sectional changes of the nasal mucosa as measured by AR with the Rhinoklack® system, and peak nasal inspiratory flow (PNIF), in atopic and nonatopic volunteers. Results: After allergen challenge, mean variation in minimal cross-sectional area (ΔMCA), as measured by AR, or in peak nasal inspiratory flow (ΔPNIF) in nonatopic volunteers, was −0.4±14.3% and 5.2±15.7%, respectively, compared to baseline. This allowed the determination of a reaction threshold of −29% for ΔMCA and of −26% for ΔPNIF. All but one of the 30 atopic patients reached the AR reaction threshold, whereas all patients reached the PNIF reaction threshold. AR and PNIF closely correlated with clinical and symptom scores for nasal congestion, since there was no significant difference at reaction threshold between both methods. Conclusions: In an allergen provocation test, AR appears to be as specific and sensitive as peak nasal inspiratory flow, with the advantage of being independent of the patient's active cooperation. Discrepancies between both methods emphasize the role of nasal cavity anatomy in measuring nasal congestion by AR.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Over a period of 5 years, an isolated light chain ‘K = 9, λ= 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti-δ- and anti-ɛ-specific antisera identified four δ heavy chains, all associated with a λ light chain, and no ɛ heavy chains. For evaluation of the role of two-dimensional polyacrylamide gel electrophoresis ‘2D-PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D-PAGE. δ Heavy chains migrated to gel areas clearly distinguishable from other heavy chains α, γ, or μ, and in a wide range of isoelectric points ‘pl: 5.4-8). In one serum, the monoclonal δ chain had a pi range comparable to that of albumin and was undetectable. However, all four δ chains were easily identified when analyzed from affinity-purified immunoglobulin fractions. These observations showed the following:1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, Ostrongly confirming the need for further analysis with anti-δ antisera, before assumption of a light-chain disease.2) 2D-PAGE analysis of affinity-purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases.3) However, although 2D-PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time-consuming and expensive, and does not appear suitable for routine practice as a first-line diagnostic procedure.2D-PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 52 (1997), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1434-9949
    Keywords: Key words:Cyclophosphamide – Heart failure – Mixed connective tissue disease – Myocarditis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: A 30-year-old woman with mixed connective tissue disease was admitted with Wernicke’s aphasia and progressive dyspnoea with chest pain. Multiple brain infarcts on a computed tomographic scan were compatible with a thromboembolic aetiology. Echocardiography showed marked hypokinesia of the posterior wall, biventricular dilatation and a decreased left-ventricle ejection fraction (40%). A diagnosis of myocarditis was made on myocardial biopsies disclosing interstitial lymphocytic infiltrates and myocardial fibre necrosis. A treatment with steroids and monthly pulsed cyclophosphamide was introduced. The heart function rapidly improved as assessed by a left-ventricle ejection fraction of 55% and remained stable 17 months thereafter.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical microbiology & infectious diseases 18 (1999), S. 871-878 
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Around 5–10% of adults infected with hepatitis B virus (HBV) develop a chronic liver disease such as chronic active hepatitis (CAH), and it is unclear whether the clinical outcome depends solely on the immune response or whether viral factors also play a role. In this study, a search was therefore made for nucleotide mutations in the basic core promoter (BCP) and amino-acid substitutions in the precore/core region of HBV infecting patients with CAH or with acute hepatitis. The nucleotide sequences of the BCP and of the precore/core region were determined in virus from ten patients with CAH and ten with acute hepatitis. The precore/core sequences were also analysed in 14 additional patients (6 with CAH, 8 with acute hepatitis). In seven of the ten patients with CAH, five types of mutations were found in the BCP. Deletions in the precore/core region were observed in six patients. In all six patients where only the precore/core region was studied, amino-acid substitutions were present. In contrast, in the ten patients with acute hepatitis studied for BCP, a mutation was found in the BCP of one patient only. Of the 18 patients in whom the precore/core was studied, three had an amino-acid substitution in this region. The results show a clear link between CAH and both HBV BCP and precore/core region mutations, suggesting these mutations may play a role in the persistence of HBV infection.
    Type of Medium: Electronic Resource
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