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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 91 records · Page 5Linked to original sources
PubMed2000

Multifocal fixed drug eruption to paracetamol, tropisetron and ondansetron induced by interleukin 2.

Fixed drug eruptions (FDEs) represent an uncommon subset of drug reactions where typically dusky red skin eruptions recur at the same site each time a drug is administered. Multifocal FDEs are defined by skin eruptions at more than one site. We describe a patient with metastatic melanoma who developed a multifocal FDE to paracetamol, tropisetron and ondansetron during chemoimmunotherapy with interleukin 2 (IL-2) and dacarbazine. This case is unique since to our knowledge there has been no previous report of such a drug reaction to tropisetron. Moreover, recurrences were induced by drugs which were chemically unrelated (i.e. tropisetron and paracetamol). We propose that this unusual skin reaction to multiple drugs was induced by IL-2 administered during immunochemotherapy for the metastatic melanoma.

Acetaminophen↗
PubMed2000

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↗
PubMed2000

Primary cutaneous T-cell-rich B-cell lymphoma and Hodgkin's disease in a patient with Gardner's syndrome.

A 50-year-old patient, suffering from familial polyposis (Gardner's syndrome), initially presented with several nodules on his left arm. Histological examination revealed primary cutaneous T-cell-rich B-cell lymphoma (TCRBCL). Staging procedures failed to detect any systemic involvement. Three years after total excision of the tumours, the patient presented with a non-specific dermatitis, enlarged axillary lymph nodes and splenomegaly. Histological and immunohistochemical examination of lymph node and spleen biopsy specimens resulted in the diagnosis of Hodgkin's disease (HD) of the nodular sclerosis type. Sequence analysis of single cells micromanipulated from skin and from lymph node lesions indicated that both lymphoma infiltrates were derived from the same precursor germinal centre B-cell clone. This is a case showing a clonal relationship between TCRBCL and HD, providing support to the B-cell origin of Hodgkin and Reed-Sternberg cells.

Gardner Syndrome↗
PubMed2000

Cutaneous T-cell lymphomas: prognosis and quality-of-life issues.

Cutaneous lymphomas (CL) include lymphocytic malignancies derived from B cells, T cells, or other cell types such as natural killer cells. Cutaneous T-cell lymphomas are the most common CL, especially mycosis fungoides, Sézary syndrome, and the spectrum of large-cell CD30(+) lymphoproliferative disorders. It is important to understand that these diseases have a much better prognosis than their nodal counterparts; therefore, treatment has to be stage adapted and palliative. Due to the anatomical localization, these lymphomas have significant impact on the quality of life of the patient.

Humans↗
PubMed2000

Historical perspective on the use of retinoids in cutaneous T-cell lymphoma (CTCL).

Vitamin A and its analogues influence differentiation and proliferation and may also alter immune responses. Limited clinical efficacy of these compounds given alone or as part of a combination therapy has been shown in various types of cutaneous T-cell lymphoma (CTCL), including mycosis fungoides, Sézary syndrome, and prelymphomatous disorders such as parapsoriasis en plaques. Compounds used mostly in small, nonrandomized trials are isotretinoin (13-cis-retinoic acid), etretinate, acitretin, and all-trans-retinoic acid. Clinical responses have been found despite persistent residual disease with atypical lymphocytes in various compartments. The exact mechanism of action of retinoids in CTCL is unclear and depends on the presence of retinoid receptors on the tumor cells, which is variable in different forms of CTCL. Therapies combining retinoids with psoralen-ultraviolet A or with interferons may have a synergistic effect, which deserves confirmation through randomized trials in the future.

History, 20th Century↗
PubMed1999

Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia.

BACKGROUND: The cause of persistent eosinophilia and the hypereosinophilic syndrome is unknown. Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5, a cytokine required for the growth and differentiation of eosinophils. We examined T-cell surface markers, rearranged T-cell-receptor genes, and in vitro production of cytokines by T cells from patients with idiopathic eosinophilia. METHODS: The expression of surface molecules on T cells was measured by flow cytometry. Cytokine expression was measured by enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemical analysis. To identify dominant (clonal) rearrangements of the T-cell receptor within the lymphocyte population, Southern blot analysis (beta chain) and the polymerase chain reaction (gamma chain) were performed according to standard protocols. RESULTS: Among 60 patients with idiopathic eosinophilia, 16 had circulating T cells with an aberrant immunophenotype. In each of these patients, the abnormal immunophenotype was unique. Evidence of clonal rearrangements of the T-cell receptor was obtained in 8 of the 16 patients. In most instances, the abnormal T cells expressed large amounts of surface proteins associated with T-cell activation (the alpha chain of the interleukin-2 receptor and the HLA-DR antigen). Moreover, the aberrant T cells produced large amounts of interleukin-5 in vitro. CONCLUSIONS: Clonal populations of abnormal T cells producing interleukin-5 occur in some patients with idiopathic eosinophilia.

Adult↗
PubMed1999

Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-gamma in melanoma cell cultures established from CNS lesions.

In advanced stages of malignant melanoma (MM), metastases to the CNS are frequently observed. Few results are available on trophic factors and immunological features involved in the process of invasion and adhesion of circulating metastatic cells into the CNS. A direct comparison of remote metastases found in different locations of the same patient might help to identify such properties. For this purpose, we screened a panel of MM cell cultures, which had been established from patients with surgically removed MM lesions of the CNS, for expression and regulation of immunorelevant molecules. The results were compared with standard controls and cultures established from non-CNS metastatic lesions of the same patients. No significant differences were observed for expression of HLA-I, HLA-II, ICAM-1 and the melanoma-associated antigens Mage-3, MelanA and tyrosinase. Constitutive expression of the neuronal cell adhesion molecule (NCAM) was found in all CNS-derived samples and in fewer than 50% of non-CNS derived cultures. IFN-gamma was found to have a weak up-regulating effect in all non-CNS-derived cultures, except normal melanocytes. However, in 6/7 CNS-derived cultures, pre-treatment with IFN-gamma reduced expression of NCAM to 28% to 77% of the level in untreated cultures. The presence and regulation of NCAM differs between MM cells derived from CNS metastases and non-CNS-derived melanocytic cells. Thus, NCAM might be a candidate immunoregulating molecule involved in the formation of CNS metastases of MM.

Antibodies, Monoclonal↗
PubMed1999

[Delay of the diagnosis of an amelanotic malignant melanoma due to CO2-laser treatment--case report and discussion].

The incidence of malignant melanoma is steadily increasing. The best prognostic indicator of melanoma is the vertical tumor thickness. Early recognition of melanoma by the naked eye is often difficult, because many lesions simulate its clinical presentation. We report on a 47-year-old man with a red papular skin lesion treated by CO2 laser. The histological diagnosis of an amelanotic malignant melanoma was thus delayed for one year. Clinically ambiguous skin tumors should never be treated by laser prior to a diagnostic biopsy.

Carbon Dioxide↗
PubMed1999

[UV exposure in Switzerland: time- and topography-associated factors important for the skin].

The intensity of UV-A and UV-B-radiation in Switzerland shows big differences that result from the various altitudes, the season and the time of the day. Additionally the intensity of UV-radiation is influenced by other factors like aerosols, cloudiness and ozone. In higher altitudes there is an additional enhancement by reflection of snow. The most important consequences of the UV-radiation for the population are, however, relevant in spring and summer time during the bathing season and during the late winter season for ski tourists. On a day with a clear sky in summer the UV-radiation can reach maximum values for UV-A of 45 W/m2 and for UV-B of 0.175 W/m2. The ratio of UV-A/UV-B shows an annual course with a maximum in winter of about 500 and a minimum of about 220 in summer. The possible effects on health by extensive UV-exposition are photoageing, skin cancer, inflammation processes and cataract. In Switzerland about 5000 new melanoma cases in men and about 4000 in women occur per year. In contrast to other environmental factors like pollen UV-radiation has the big advantage that the personal exposition can be controlled. Therefore, it is very essential that the general rules of a judicious behaviour such as avoiding the sun at noon, always wearing a hat, shirt and trousers as well as sunglasses with UV-filter are often reiterated.

Female↗
PubMed1999

Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.

BACKGROUND: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. METHODS: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. RESULTS: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. CONCLUSIONS: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.

Aged↗
PubMed1999

Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells.

Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and "supershift" assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

Adult↗
PubMed1999

Tumor burden index as a prognostic tool for cutaneous T-cell lymphoma: a new concept.

OBJECTIVES: To introduce a prognostic tool for cutaneous T-cell lymphoma that takes into account the tumor burden and to compare the prognostic value of this tumor burden index (TBI) with that of other prognostic factors. DESIGN: Retrospective clinical and statistical study. PATIENTS: One hundred sixteen patients with cutaneous T-cell lymphoma. METHODS: A TBI was designed that takes into account the types, numbers, and severity of skin lesions with the use of the Cox proportional hazard model. RESULTS: Models of the TBI were developed to test the relative contributions of patches, plaques, and tumors to the total tumor burden and, hence, survival time. Weighting factors reflecting the severity of each skin lesion were tested and incorporated. The best prognostic correlation was a dichotomized index with the following formula: TBI = 1 + (patches x 2) + (plaques x 2) + (tumor x 1.3), where the patches factor equals 0 if 30% or less of the skin area is involved and 1 if greater than 30% of the skin area is involved and where the plaque or tumor factor equals 1 if plaques or tumors are present. Both the TBI and TNM provided predictive information. Discrimination of survival curves and significance of differences was better for TBI (P < .001) than for TNM (P = .009). Sex was also statistically related to survival (males had a better prognosis; P < .04), whereas neither age at first symptoms (P = .35) nor age at time of diagnosis (P = .36) was of prognostic value. CONCLUSIONS: The TBI offers a simple prognostic index for the evaluation of cutaneous T-cell lymphoma. It may become a valuable tool for designing therapeutic strategies for patients according to their specific survival expectancies. However, this model is preliminary and has to be validated on a larger number of patients.

Adolescent↗
PubMed1999

IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity?

IL-12 enhances cytolytic activity and proliferation of NK and T cells, and induces cytokines such as IFN-gamma. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on melanoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the beta chain of the IL-12 receptor (IL-12Rbeta). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhesion molecule (ICAM)-1 of those cultures with IL-12Rbeta expression. The effects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing monoclonal antibody (mAb), but not by an mAb against IFN-gamma. Melanoma cells transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells with allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhanced proliferation and increased production of IL-2 and IFN-gamma after pretreatment with IL-12. IL-12 pretreatment increased the susceptibility of melanoma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced immunocritical surface molecules on melanoma cells, it might be beneficial during immune interventions in melanoma patients.

Antibodies, Monoclonal↗