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Biomedical subjects

L Heinzerling

Publications and source records attributed to L Heinzerling.

8 recordsLinked to original sources

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents.

Antirheumatic Agents↗

[Immuno-intervention in cutaneous lymphomas].

Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders. Most of the cutaneous lymphomas present a rather good prognosis because they disseminate to internal organs late in the disease process, if at all. Since radiotherapy and intensive chemotherapy have limited efficacy, immunological interventions are regularly used in this disease group. These interventions include unspecific treatment modalities such as Interferon-alpha, Interleukin-2, but also rather specific interventions like photopheresis, fusion toxins and as a new development, antigen-loaded dendritic cells. A new humanized anti CD20-antibody can be used for patients with cutaneous B-cell lymphomas, expressing the B-cell antigen CD20 in most of the cases. We expect that new information on the immunobiology of these diseases will allow more specific immunological interventions, providing the basis for a better therapy with optimal tolerability for patients suffering from cutaneous lymphomas.

Humans↗

Intralesional therapy with anti-CD20 monoclonal antibody rituximab in primary cutaneous B-cell lymphoma.

BACKGROUND: We report the use of a new treatment modality in 2 patients with primary cutaneous B-cell lymphoma. In a 58-year-old woman with progressive nodular lesions on the scalp and face, several treatment attempts either failed or could not be used because of severe adverse effects and underlying epilepsy. The patient declined radiotherapy. A 30-year-old man presented with recurrence of tumor nodules occipitally, thoracically, on the arm, and on the right thigh after several excisions. OBSERVATIONS: Intralesional injection of rituximab, a chimeric antibody directed against the CD20 transmembrane antigen present in malignant and normal B cells, resulted in partial regression of tumor nodules. No adverse effects occurred except pain during or shortly after injection and, in one patient, a slight rise in body temperature. Due to the treatment a prolonged complete disappearance of B cells from peripheral blood samples was observed. CONCLUSION: Intralesional rituximab therapy is a nontoxic and effective treatment for cutaneous B-cell lymphoma that deserves further investigation in larger clinical trials.

Adult↗

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA.

We have recently demonstrated that DNA coding for both subunits of the murine IL-12 heterodimer exhibits a strong antimetastatic effect against B16-melanoma in C57BL/6 mice and after intratumoral injection tumor regression. Here we show that the antimetastatic effect can be detected when the DNA is injected intramuscularly 30 days before tumor cell challenge. A long-term IL-12 expression was measured for up to 50 days in the serum with a peak at day 20 amounting to about 10 ng/mL in C57BL/6 mice. CpG oligodeoxynucleotides also induce IL-12 expression, however, only for a few hours. IL-12 DNA administration induces long-lasting systemic IFN -gamma production, whereas IL-4 and TNF-alpha levels remained undetectable. NK cell-depleted mice showed a strong but reduced expression of murine IL-12. Expression of DNA encoding human instead of murine IL-12 resulted in a significantly lower and transient expression, indicating that not plasmid-derived IL-12 production alone but the immune system of the host contributes to the long- lasting antimetastatic effect. It may be attributable to an autocrine feedback mechanism maintaining murine IL- 12 expression, whereby several cell populations including NK cells are involved.

Animals↗

Cutaneous ulceration after injection of polyethylene-glycol-modified interferon alpha associated with visual disturbances in a melanoma patient.

Interferons are used in the therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma. Their short half-life that requires frequent injections can be increased by polyethylene glycol (PEG) modification. A 50-year-old patient was diagnosed as having an acrolentiginous melanoma (Breslow >5 mm, Clark level IV) and inguinal lymph node metastases. After surgical excision and lymphadenectomy, immune therapy with 6.0 microg pegylated interferon alpha(2b)/kg body weight, s.c., was started. Cutaneous ulcerations at the injection sites developed 9 months after treatment initiation. The patient also developed blurred vision and presented with binasal scotomas and pathological visually evoked potentials and electroretinogram. The cutaneous ulcerations slowly healed under local therapy and reduction of the concentration of the PEG-modified interferon from 0.86 to 0.43 mg/ml. The dosage was maintained. Two months later, the therapy was stopped due to disease progression. Vision subsequently recovered. Cutaneous reactions evolved at the sites of subcutaneous injections of PEG-modified interferon alpha(2b). Changes in vision can probably be attributed to immunotherapy.

Humans↗

Enhanced protection against viral infection by co-administration of plasmid DNA coding for viral antigen and cytokines in mice.

BACKGROUND: DNA vaccines have been shown to induce protective immunity against viral infections in different animal models. We have recently demonstrated that DNA vaccine induced protective immunity against influenza A virus and La Crosse virus (LACV) is primarily mediated by humoral immune response. OBJECTIVE: The goal of this study was to investigate whether administration of DNA coding for cytokines such as interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) could increase the protective immune response induced by vaccination with DNA coding for viral antigens. STUDY DESIGN: For the influenza A virus or LACV model, C57BL/6 or interferon-alpha/beta receptor (IFNAR-1)-deficient mice, respectively, were vaccinated once or twice with 100 micrograms of DNA encoding viral antigens. At the same time plasmid DNAs (100 micrograms) coding either for mouse GM-CSF or mouse IL-12 were administered. The mice were subsequently challenged with a lethal dose of influenza A virus or LACV and monitored for clinical symptoms (weight loss) and survival. RESULTS: To achieve a high degree of protection (70% survival) two injections of DNA encoding the influenza A virus surface protein hemagglutinin (HA) were required. Intriguingly, administration of DNA coding for IL-12 alone also led to a pronounced protective effect against virus challenge. Co-administration of DNAs encoding IL-12 and HA significantly increased the protective immunity against influenza A virus, while IL-12 expression did not improve protection upon vaccination with DNA coding for the internal nucleocapsid protein N of LACV. Co-injection of DNA coding for mouse GM-CSF and HA also showed an adjuvant effect. CONCLUSIONS: The data clearly indicate that co-administration of DNA encoding cytokines such as IL-12 and GM-CSF with DNA coding for viral antigens has adjuvant effects on the protective immune response against different viral pathogens.

Animals↗