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Biomedical subjects

G Burg

Publications and source records attributed to G Burg.

At least 289 records · Page 16Linked to original sources

[Acetylsalicylic acid-induced generalized pustulosis].

We report the case of a 55-year-old patient with recurrent episodes of generalized pustulosis and febrile temperatures. Histological examination revealed subcorneal and spongiform pustules. After a 4 years' course acute exanthematous generalized pustulosis, induced by acetylsalicylic acid was diagnosed. Clinical features, differential diagnosis and causative agents of this rare drug reaction are discussed.

Acute Disease↗

Topical administration of hexadecylphosphocholine in patients with cutaneous lymphomas: results of a phase I/II study.

BACKGROUND: Hexadecylphosphocholine is a new antineoplastic drug that inhibits tumor cell growth directly and, in addition, might have immunoregulatory properties. OBJECTIVES: We investigated the topical application of this phospholipid in patients with cutaneous lymphoma. METHODS: Twenty-four patients with histologically documented cutaneous lymphoma were treated for 8 weeks. Lesions that responded to treatment were biopsied and evaluated histologically. RESULTS: Of 15 patients with cutaneous T-cell lymphomas, 12 were evaluable. Two complete remissions, four partial remissions, and one minor remission were observed. Of seven patients with B-cell lymphomas, six were evaluable. One complete remission, three partial remissions, one case of stable disease, and one case of progressive disease were seen. However, histologic monitoring demonstrated only a partial clearing of infiltrating lymphocytes in lesions that showed a partial or complete response clinically. Both patients with lymphomatoid papulosis had complete clearing of the lesions clinically. An objective response rate (partial and complete response) of 56% (10/18) was achieved in the patients with cutaneous lymphoma who were treated in this study. CONCLUSION: Hexadecylphosphocholine appears to be effective topically in the treatment of some cases of cutaneous lymphomas.

Administration, Cutaneous↗

Lesion-specific activation of cloned human tumor-infiltrating lymphocytes by autologous tumor cells: induction of proliferation and cytokine production.

To investigate the mechanisms by which tumor-infiltrating lymphocytes exert their antitumor effects, tumor-specific tumor-infiltrating lymphocyte clones, as well as autologous tumor cell lines from primary and secondary tumors of two patients during the course of melanoma progression were established. Enrichment for tumor-infiltrating lymphocytes expressing CD25, as well as low concentrations of interleukin-2 (30 IU/ml) in the culture medium, led to a preferential outgrowth of cells that express the high-affinity interleukin-2 receptor. All of these expressed CD2, CD3, CD11, and CD25. Coculture of tumor-infiltrating lymphocyte clones with irradiated, autologous tumor cells induced an up to 480% greater proliferative responses than recombinant interleukin-2 alone. Approximately 60% of the tumor-infiltrating lymphocyte clones showed cytotoxicity against the relevant tumor in a 4-h 51Cr-release assay. When tested in an 18-h 51Cr-release assay, the number of tumor-infiltrating lymphocyte clones exhibiting cytotoxicity against the relevant tumor increased to over 85%. In response to autologous tumor cells, nine of 15 clones secreted interferon-gamma, tumor necrosis factor-alpha, or both. Cytokine production was not restricted to either CD4+ or CD8+ T cells because both CD4+ and CD8+ tumor-infiltrating lymphocyte clones secreted cytokines. Tumor-infiltrating lymphocyte tumor interaction appears to be lesion specific because induction of proliferation and cytokine production, as well as susceptibility to cytolysis, was found not only restricted to the autologous system, but also to the specific lesion. The pattern of tumor-infiltrating lymphocyte tumor interaction specificity indicates a possible loss of antigens expressed on the tumor during disease progression.

Cell Division↗

T cells migrate to tumour sites after extracorporeal interleukin 2 stimulation and reinfusion in a patient with metastatic melanoma.

Peripheral blood mononuclear cells (PBMC) were taken by leukapheresis from a patient with melanoma skin metastases and stimulated in vitro using 1000 IU recombinant interleukin 2 (IL-2)/ml to generate lymphokine-activated killer cells (LAK cells). Two-colour immunofluorescence analysis demonstrated an IL-2-induced up-regulation of CD25 on natural killer cells (CD56+) as well as on T lymphocytes (CD3+). After radiolabelling with indium-111, the cells were reinfused. Gamma-camera imaging revealed an enrichment at the tumour sites. Immunostaining of tumour tissue taken before and after scintigraphy demonstrated CD25+ T lymphocytes (CD2+, CD3+), but no natural killer cells (CD16+, CD56+) infiltrating the metastases. LAK cell enrichment at melanoma metastases in vivo did not involve natural killer cells, but was characterized by increased numbers of activated T lymphocytes in this patient.

Cell Movement↗

Evidence for cell-mediated immune mechanisms in the pathology of pemphigus.

Pemphigus is an autoimmune blistering disease in which autoantibodies have clearly been shown to be pathogenic. Because autoantibodies are also found in uninvolved skin, further mechanisms may be important in the development of pemphigus lesions. In addition to granulocytes, mononuclear cells are commonly found in pemphigus lesions. To elucidate the role of mononuclear cells in the pathology of this disease, we determined the levels of soluble interleukin-2 receptor in blister fluid and serum samples from pemphigus patients prior to treatment. The interleukin-2 receptor (IL-2R) is expressed on activated mononuclear cells. Depending on its rate of synthesis, a portion is released from the cell surface in a soluble form (sIL-2R). In blister fluid, sIL-2R levels were 2186 +/- 288 U/ml (+/- SD), which was significantly higher than levels in concurrently obtained serum samples (1299 +/- 165 U/ml; P < 0.001). In suction blisters in volunteers, and in patients with second-degree burns or friction-induced bullae, sIL-2R levels were normal in both blister fluid and serum. In pemphigus patients, sIL-2R serum levels continuously declined during systemic therapy, correlating with disease activity. Immunohistological studies demonstrated a marked increase in IL-2R+ cells in both the epidermis and dermis of lesional skin compared with perilesional skin. In the dermis, CD3+ T cells predominated, whereas monocytes/macrophages were most frequent in the epidermis. In pemphigus vulgaris, monocytes/macrophages were restricted to the basal keratinocytes, whereas in pemphigus foliaceus, they were found throughout the lesional epidermis. Our data indicate that activated mononuclear cells are present in lesional skin of pemphigus patients, and may contribute to the pathology of this disease.

Aged↗

Tumour-infiltrating lymphocytes in primary melanoma: functional consequences of differential IL-2 receptor expression.

Tumour-infiltrating lymphocytes (TIL) have been isolated from early primary melanoma (Clark level III) and expanded in vitro using culture conditions with low concentrations of IL-2 (50 U/ml). Immediately after isolation TIL consisted of mainly CD3+ T cells, and the portion of CD56+ natural killer (NK) cells was below 20%. Fresh TIL cultures could be distinguished by CD25 expression since some contained up to 33%, others less than 5% CD25+ cells. These showed differences in subsequent development during in vitro expansion. CD25-expressing cultures remained stable in their phenotype, whereas the second TIL type showed major changes: CD3 (ca 70-30%) expression decrease, CD25 (ca 5-35%) and CD56 (ca 15-55%) expression increase. The TIL type, which remained dominated by CD3+ T cells, killed autologous tumour cells efficiently (51Cr-release greater than 30% at a E/T ratio of 20:1), which could be blocked by MoAbs against MHC class I molecules. In contrast, the other TIL type exhibited weak cytotoxicity (less than 17% 51Cr-release at an E/T ratio of 20:1) against the autologous tumour. Therefore, the expression of CD25 on freshly isolated TIL is a good marker for tumour specificity of in vitro expanded TIL.

Antigens, CD↗

Allergic contact dermatitis from natural latex without contact urticaria.

During the last decade, there have been many reports of immediate-type hypersensitivity to natural latex, resulting in contact urticaria, generalized allergic reactions such as urticaria and Quincke's edema, and asthmatic or anaphylactic reactions. Moreover, delayed-type hypersensitivity to rubber additives such as thiuram and carbamate derivatives is acknowledged to be the main cause of dermatitis in patients working with rubber gloves. We here report on a patient who developed severe dermatitis on his hands and forearms 3 months after he had started working with rubber gloves. Patch tests with rubber additives, skin prick tests and RAST to natural latex were negative. However, a delayed type of hypersensitivity to latex could be shown by a positive patch test. To our knowledge this is the 1st case reported of an isolated contact dermatitis from natural latex without contact urticaria to latex or hypersensitivity to rubber additives. We therefore propose that not only patch tests with rubber additives, but also skin prick and patch tests with latex should be performed in contact dermatitis patients working with rubber gloves.

Adult↗

Idiopathic middermal elastolysis.

A 42-year-old white woman experienced widespread fine wrinkling and perifollicular protrusions in areas of erythematous patches with obvious photodistribution. Histological examination of the affected skin revealed loss of elastic tissue limited to the middermis. The clinical and histological presentation meets the criteria for the diagnosis of idiopathic middermal elastolysis. These findings support the previously postulated inflammatory pathogenesis for the loss of middermal elastic tissue and suggest that sun exposure may be a contributing factor. Idiopathic middermal elastolysis may represent only a variant in a spectrum of acquired wrinkling due to elastolysis with varying histological and clinical findings.

Adult↗

Collision dermatosis: angiolymphoid hyperplasia with eosinophilia developing within a congenital port wine nevus.

This is the report on a 22-year-old man suffering since birth from a port wine nevus at his left shoulder, which at the age of 21 showed slight thickening in the central area of the lesion. Histology revealed typical features of nevus flammeus at the border zone and in the newly developing central area proliferation of dilated vessels with prominent endothelial walls surrounded by dense lymphoid cell infiltrates containing many eosinophils and lymph-follicle-like structures in the mid and deep dermis, compatible with angiolymphoid hyperplasia with eosinophilia (ALHE). This is the first report of ALHE occurring in a congenital port wine nevus indicating microenvironmental importance for vascular reactive or neoplastic proliferations. The relationship to Kimura's disease will be discussed.

Adult↗

Acute generalized exanthematous pustulosis due to doxycycline.

Sterile epidermal neutrophilic pustulation can be observed in a variety of diseases. Though drug hypersensitivity is an uncommon cause, it is yet a known entity to be considered in the differential diagnosis of generalized pustulosis. In a 40-year-old woman, who developed a generalized pustular eruption after starting on doxycycline therapy of bronchitis, the rash was concluded to be drug induced after exclusion of other pustular dermatoses. Sensitization to doxycycline was demonstrated by in vitro lymphocyte testing and correlated with clinical drug hypersensitivity after recurrence of the pustular eruption on nonintentional rechallenge with doxycycline.

Acute Disease↗

Cutaneous ossification in Albright's hereditary osteodystrophy.

A 23-year-old woman presented with subcutaneous ossification, which together with short stature, stocky physique, round face and brachydactyly suggested Albright's hereditary osteodystrophy (AHO). Serum calcium and phosphorus levels were normal. AHO refers to the phenotype of the syndromes of pseudo-hypoparathyroidism (PHP) type Ia and pseudopseudohypoparathyroidism (PPHP), both considered genetically related variants with a defect of the alpha subunit of the stimulatory G protein of adenylate cyclase, necessary for the action of parathyroid and other hormones using cyclic AMP as an intracellular second messenger. PPHP differs from PHP in that it lacks parathyroid hormone resistance manifesting itself as hypocalcemia. Other endocrine end organ unresponsiveness, e.g. hypothyroidism and hypogonadism, may also be found with PHP. Both PHP and PPHP usually exhibit characteristic phenotypic abnormalities, of which subcutaneous ossification may be a presenting feature. The differential diagnosis of cutaneous calcification and ossification is outlined.

Adult↗

Generalized eczematous skin rash possibly due to HMG-CoA reductase inhibitors.

We report on 3 patients who developed a generalized eczematous skin rash under treatment with simvastatin and pravastatin for hypercholesterolemia. These drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and suppress cholesterol synthesis in the liver. Based on experimental data from the literature that showed eczematous changes in mice treated topically with the HMG-CoA reductase inhibitor lovastatin, we suspect that the rash observed in our patients may be a consequence of skin barrier dysfunction following inhibition of cholesterol biosynthesis.

Anticholesteremic Agents↗

Irritant reactivity is a better risk marker for nickel sensitization than atopy.

In order to optimize patch test strategies and counselling in occupational dermatology, it is important to identify risk markers of contact sensitization. Since nickel is the most frequent contact allergen in European countries, we studied the potential of the irritant response to sodium lauryl sulfate (SLS) to predict nickel sensitization. In 100 patients subsequently tested in our patch test clinic with the standard patch test series of the German Contact Dermatitis Group (DKG), the atopy score as described by Diepgen et al. was determined and an SLS patch test was performed. Relative transepidermal water loss (TEWL), expressed as the ratio between the TEWL of the SLS-irritated and the control site, atopy score, age and sex were tested by logistic regression analysis for their association with patch test-proven nickel sensitization. Age, sex and relative TEWL were found to be significant predictors of nickel sensitization, whereas the atopy score was not. Patients with nickel sensitization were significantly younger (mean age 35.0 +/- 4.1 versus 46.2 +/- 2.1 years), more frequently of female gender (28.6% versus 3.9%) and had a significantly higher relative TEWL following SLS exposure (471.0 +/- 40.8% versus 344.0 +/- 16.2%). The mean atopy score of nickel-sensitized patients was slightly higher than that of patients not sensitized (6.0 +/- 1.3 versus 5.3 +/- 0.5), but the difference was not significant. In previous studies on larger patient samples, atopy was found to be a predictor of nickel allergy. This discrepancy may be explained by the smaller statistical power of our study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Malignant melanoma of the skin].

The frequency of malignant melanoma is increasing worldwide and comprises in middle Europe about 10 per 100,000 inhabitants per year; it is fatal in each forth or fifth patient. Risk factors may be endogenous, like fair skin with high sensitivity for sun exposure and the presence of many, possibly atypical ('dysplastic') naevi, or exogenous, e.g. excessive exposure to ultraviolet light. The superficial spreading malignant melanoma is the most common form of clinical manifestation. Applying the A (asymmetry), B (border), C (color), D (diameter), E (elevation) rule is a reliable help for making the diagnosis of malignant melanoma. The differential diagnosis besides various naevi comprises a wide spectrum of pigmented new formations of the skin. Classification of malignant melanoma follows the TNM system; spread, tumor thickness and/or level of infiltration are appropriate parameters. The most important prognostic parameter is tumor thickness, which results in 10-year survival time of only 30% if it exceeds 3 mm. The therapy of malignant melanoma is performed by excision with margins between 1 and 3 cm, depending on tumor thickness. Frequency and type of investigations for follow-up controls depend on the risk for metastases, i.e. on tumor thickness. Best prevention is achieved by avoiding excessive exposure to ultraviolet light, especially during childhood, and by early diagnosis of thin melanoma.

Combined Modality Therapy↗