Search PubMed⌕ Search

Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 109 records · Page 6Linked to original sources

Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis.

BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.

Administration, Cutaneous↗

Detection of circulating melanoma cells by specific amplification of tyrosinase complementary DNA is not a reliable tumor marker in melanoma patients: a clinical two-center study.

PURPOSE: Recently, the reverse-transcription polymerase chain reaction (RT-PCR) of tyrosinase messenger RNA (mRNA) was reported to be a useful tool for the detection of circulating tumor cells in the peripheral blood of melanoma patients. Our aim was to evaluate critically the diagnostic value of this marker by investigating a significant number of patients in different stages of the disease in a two-center study. PATIENTS AND METHODS: Different techniques of blood collection, RNA isolation, and RT-PCR were compared, and the detectability of tyrosinase mRNA was tested using nine different melanoma cell lines. The sensitivity of the method was confirmed by blood spiking experiments and the specificity by restriction enzyme analysis. Subsequently, a total of 153 blood samples from 137 individuals (30 healthy subjects, five basal cell carcinoma, and 102 melanoma patients) were investigated. RESULTS: The detection level of melanoma cells differed between the cell lines tested. However, we could reproducibly detect single melanoma cells by spiking whole blood samples from healthy volunteers. One of 43 patients with primary melanoma (2.3%), zero of 15 patients with regional metastasis (0%), and 12 of 44 patients with advanced disease (27.3%) were found to be RT-PCR positive. All blood samples obtained from controls and patients with basal cell carcinoma were tyrosinose mRNA negative. CONCLUSION: Our data support the recent doubts that the detection of circulating tumor cells in melanoma patients using the tyrosinase mRNA RT-PCR is not sensitive enough to be used either as a melanoma progression marker in early stages of the disease or to monitor therapy in advanced stages of the disease.

Biomarkers, Tumor↗

[Merkel cell carcinoma: follow-up of 10 patients. Current diagnosis and therapy].

Merkel cell carcinoma (MCC) is a rare neoplasm of the skin predominantly found on the head and extremities. Clinically MCC presents as a rapidly growing red or violaceous, dome-shaped, solitary tumor. The clinical and histological diagnosis of MCC remains difficult. Distinction from poorly differentiated small cell primary tumors or metastasis requires immunohistochemical analysis and-if available-electron-microscopic studies. We report on the follow-up of 10 patients with MCC treated in the past 6 years at our department. In nine patients the tumors were completely removable; in one patient with a large primary tumor of the upper lip no histologically proven complete excision could be performed. After a median follow-up of 42 months, local recurrence or lymph node involvement was observed in three patients. Two patients died following disseminated metastases, one elderly patient due to cardiac insufficiency. Our observations demonstrate that MCC is a potentially aggressive cutaneous tumor. Adequate primary surgical and adjuvant therapy as well as careful follow-up are mandatory.

Aged↗

Increased eotaxin-mRNA expression in non-atopic and atopic nasal polyps: comparison to RANTES and MCP-3 expression.

Eosinophilic tissue infiltration of nasal mucosa typical for allergic rhinitis and chronic polypous sinusitis may be due to chemotactic activity of chemokines specific for eosinophils. The CC-chemokines eotaxin, RANTES and MCP-3 have been postulated to be involved in the recruitment of eosinophils to certain inflamed tissues. To explore their possible role in chronic polypous sinusitis we examined eotaxin-, RANTES- and MCP-3-gene expression in human nasal polyps and normal human nasal mucosa of patients undergoing endonasal surgery for treatment of chronic polypous sinusitis. Using gene-specific primers in semi-quantitative reverse-transcriptase polymerase-chain-reaction experiments we found elevated expression of eotaxin- and RANTES-mRNA but no MCP-3-mRNA in non-atopic and atopic nasal polyps when compared to normal nasal mucosa.

Adult↗

[Cryofibrinogenemia caused by monoclonal anti-fibrinogen antibodies].

HISTORY AND CLINICAL FINDINGS: For nine years a 54-year-old woman had been suffering from worsening treatment-resistant cold-dependent purpura of the limbs as well as cutaneous ulcerations and arthralgia, which recently had occurred even at a even slight decrease in room temperature. INVESTIGATIONS: A special form of cryofibrinogenemia was identified by affinity-chromatographic separation of a plasma cryoprecipitate. From this cryoprecipitate a monoclonal antifibrinogen antibody (IgG-kappa) was isolated which, in the cold, formed a precipitating complex with fibrinogen. Paraproteinaemia was not demonstrated by conventional serum and plasma electrophoresis. There was no evidence of neoplasma. TREATMENT AND COURSE: Attempted treatment with steroids, fibrinolytic agents and intravenous cyclophosphamide was unsuccessful. But long-term repeated plasmaphereses and anti-immunoglobulin adsorption improved the symptoms. After 5 years of this treatment-14 years after onset of symptoms-the patient died of the consequences of fulminant pulmonary embolism. CONCLUSION: To establish the diagnosis of monoclonal cryofibrinogenemia it is necessary, first, to identify the cryoprecipitate in plasma; secondly, to undertake affinity-chromatographic separation of the cryoprecipitate with subsequent analysis of its components.

Antibodies, Monoclonal↗

Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation.

The stratum corneum chymotryptic enzyme (SCCE) has been previously purified from human stratum corneum and resembles a chymotryptic serine endopeptidase involved in physiological detachment of corneocytes from human stratum corneum. From human stratum corneum two inhibitory activities of SCCE could be extracted. These were due to serine protease inhibitors already known to be present in human epidermis, antileukoprotease (secretory leukocyte protease inhibitor) and elafin (skin-derived antileukoprotease). The Inhibition of SCCE by antileukoprotease shows a hyperbolic, mixed type inhibition with an equilibrium dissociation constant of 63 n. Antileukoprotease also inhibits detachment of corneocytes from human plantar callus in vitro almost completely (>96%). In addition, elafin was shown to be a weak inhibitor for SCCE activity, and elafin significantly reduces the shedding of corneocytes. Thus, antileukoprotease, which is known to be produced by human keratinocytes, is likely to be the major physiological inhibitor of SCCE in the epidermis. It seems to be involved in the regulation of desquamation under physiological and pathophysiological conditions.

Aprotinin↗

Human dermal fibroblasts express eotaxin: molecular cloning, mRNA expression, and identification of eotaxin sequence variants.

Recently we discovered and purified a novel beta-chemokine with eosinophil specific chemotactic activity from supernatants to long-term TNF-alpha stimulated dermal fibroblasts. Using degenerated specific oligonucleotides based on partial amino acid sequence data and a PCR protocol, we obtained different clones sharing high sequence homology with this novel chemokine and with human eotaxin cDNA. Semi-quantitative RT-PCR experiments using eotaxin-specific primers indicate low constitutive eotaxin mRNA expression in human dermal fibroblasts which is upregulated by IL-1 alpha and TNF-alpha within 6 hrs and modulated by IFN-gamma. While IL-1 alpha-induced eotaxin mRNA accumulation is transient, long-term stimulation with TNF-alpha resulted in a further increase of eotaxin mRNA.

Amino Acid Sequence↗

Identification of an N-terminally truncated form of the chemokine RANTES and granulocyte-macrophage colony-stimulating factor as major eosinophil attractants released by cytokine-stimulated dermal fibroblasts.

Eosinophil (Eo) granule proteins and, rarely, intact Eos represent a characteristic histopathologic feature of the dermal part of affected tissue in atopic dermatitis and some allergic reactions. Dermal fibroblasts are a rich source of cytokines and inflammatory mediators; therefore, we have investigated whether these cells release Eo chemoattractants when stimulated with different stimuli. Eo-chemotactic activity was detected after stimulation of cells with TNF-alpha and IL-1, but not when phorbol ester, PHA, or medium alone was used. Biochemical characterization of Eo-chemotactic activity in supernatants of NF-alpha-stimulated cells revealed both heparin-binding and nonbinding activity. HPLC purification with subsequent N-terminal sequencing and mass spectrometric analysis showed that the heparin-binding Eo-chemotactic peak corresponded to the chemokine [Tyr-RANTES]66 that also contained [Ser-RANTES]68 as contaminant, whereas the nonheparin-binding activity was identified as granulocyte-macrophage CSF (GM-CSF) by the use of neutralizing Abs. [Tyr-RANTES]66 was found to show identical behavior in the chemotaxis assay system with respect to potency and efficacy as natural [Ser-RANTES]68. These findings support the hypothesis that dermal fibroblasts can play an important role in the recruitment of Eo by release of the chemokine RANTES together with GM-CSF.

Amino Acid Sequence↗

Monoclonal cryo-antifibrinogenemia.

We report on a 54-year-old female patient with arthritis and a severe cold-induced leukocytoclastic vasculitis of the skin caused by a rare form of cryofibrinogenemia ("type II" cryofibrinogen). Affinity chromatography of cryoprecipitates from the patient's plasma revealed reversible cryoprecipitability of complexes composed of fibrinogen and a monoclonal antifibrinogen antibody (IgG3 kappa). Conventional serum and plasma electrophoresis did not detect the paraprotein. Control of symptoms was achieved by long-term plasmapheresis.

Cryoglobulins↗

[Unusual circinary variant of generalized granuloma anulare].

We report on a 56-year-old male patient with annular, erythematous and slightly elevated lesions measuring up to 12 cm in diameter on the trunk. Histologically a diffuse mononuclear infiltrate with histiocytic giant cells was present. His condition is a rare variant of generalized granuloma annulare in association with diabetes mellitus.

Biopsy↗

[Dermatitis papulosa juvenilis].

Juvenile papular dermatosis is characterized by hypopigmented lichenoid flat papules with predilection for the dorsa of the hands, the elbows and the knees. The disease affects children in the summer months. Changes observed in biopsy specimens show hyperkeratosis, a moderate degree of acanthosis and a lymphocytic perivascular infiltrate in the upper dermis. The pathogenetic influence of such rough materials as sand and wool and of photosensitivity in atopic patients is suggested. We report on a 9-year-old boy who developed lesions of juvenile papular dermatitis (especially severe on the face and the back of the knee) and extreme pruritus for the first time in summer 1994.

Biopsy↗

[Oral exposure testing in non-aspirin-induced analgesic intolerance].

Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects.

Administration, Oral↗

Treatment of psoriasis with polyethylene sheet bath PUVA.

BACKGROUND: Bath PUVA has been shown to be an effective alternative treatment for psoriasis with fewer systemic side effects than oral methoxsalen (8-MOP). The cost of 8-MOP and the need for a bath unit have prevented wider use of this treatment. OBJECTIVE: We investigated the safety and efficacy of sheet bath PUVA by restricting the volume of the psoralen/bath water solution to 10 L with the aid of a polyethylene sheet. METHODS: Fifty-eight patients with chronic plaque-type psoriasis were treated with bath PUVA in a concentration of 0.5 mg of 8-MOP per liter of water. RESULTS: The group required a median of 17 baths (95% confidence interval [CI], 14-20) for clearance. Total UVA dose for the entire group was 26 J/cm2(95% CI, 18-47). CONCLUSION: Sheet bath PUVA is safe, efficient, and easy. This regimen can significantly reduce the amount of 8-MOP required, thereby resulting in a favorable cost/benefit ratio.

Administration, Cutaneous↗

Dermatophytes contain a novel lipid-like leukocyte activator.

In the early phase of dermatophytosis, neutrophils are regularly detected microscopically in the infected skin. Although neutrophil recruitment may at least in part occur indirectly by complement activation, we asked whether dermatophytes might release chemoattractants for neutrophils. We cultivated various strains of different dermatophytes and tested fungal extracts for the presence of neutrophil chemotactic activity. As a result, we detected neutrophil chemotactic activity only in diethylether extracts, but not in aqueous extracts. We purified this lipid-like leukocyte activator (LILA) to apparent homogeneity by reversed-phase high performance liquid chromatography and found that purified LILA does not show ultraviolet absorption at wavelengths > 210 nm. Biologic studies revealed that LILA is as effective as formyl-methionyl-leucyl-phenylalanine in eliciting neutrophil chemotaxis, degranulation, and activation of the respiratory burst. Desensitization experiments in chemotaxis and degranulation with leukotriene B4, platelet-activating factor, or 5-oxo-eicosanoids revealed that LILA does not cross-desensitize with any of these other lipid-like attractants and thus possibly acts via a distinct as yet postulated neutrophil receptor. It is hypothesized that LILA, similarly to formylated methionyl peptides in bacteria, represents a dermatophyte- and possibly fungus-specific lipid compound that allows the host phagocytes to specifically recognize fungal infection. This system would be similar to the recognition of bacteria by phagocytes via N-formylated methionyl peptides, which represent a characteristic and unique system to identify bacteria.

Arthrodermataceae↗