Bibliothek

Notizen: An aromatic retinoid (Ro-10/9359) was used for oral treatment of five cases of ichthyosis (three lamellar, two X-linked).Complete clearing of the skin lesions was achieved in all five patients within 24.2±3.2 days (X-linked 21.75±6.5, lamellar 23 days). Histopathology showed reduction of the hyperkeratosis, and thickening of the granular layer.Clinical side effects were of mild intensity and included cheilitis, conjunctivitis and pruritus. All side effects were reversible upon reduction of the daily dosage.In three patients treatment was discontinued after clearing of lesions. Fresh lesions re-appeared 6 weeks later.One patient with X-linked ichthyosis developed two recurrences during maintenance treatment; one patient with lamellar ichthyosis was kept in complete remission for 9 weeks on a reduced daily dosage.

Notizen: This is a report on a 67-year-old female patient with Graves' disease and extensive pretibial myxedema. Linear IgM deposits were observed in the basement membrane zone by direct immuno-fluorescence. These deposits were found, by immunoelectron microscopy, to be haphazardly distributed in the uppermost dermis without any correlation to preexisting structures. An amorphous material that coated not only the surface of fibroblasts and collagen bundles but was also present within the dilated endoplasmic reticulum of the fibroblasts was the predominating pathological finding at the ultrastructural level. Mast cells were morphologically normal. These results support previous in vivo and recent in vitro findings indicating that the fibroblast plays a major role in the pathogenesis of pretibial myxedema.

Notizen: A multistep immunocytochemical method, utilizing horseradish peroxidase as an immunological bound marker enzyme, was employed to demonstratein vivo fixed immunoglobulins (IgG, IgM) in the skin of three patients with CDLE and three patients with SLE. The immunoglobulin deposits were confined to the uppermost strata of the dermis, i.e. the area just below the basal lamina. Small amounts of immunoglobulin were visible within the lamina lucida and the basal lamina. Only quantitative differences were observed between deposits of immunoglobulins in CDLE and SLE. In CDLE, the reaction product covered a wider area of the superficial dermis and extended deeper down into the dermis. IgG and IgM deposits exhibited an identical fine structural morphology.

Notizen: Two novel interleukin-24 (IL-24) splice variants were identified in normal human melanocytes by sequencing cloned polymerase chain reaction (PCR) products that are not expressed in metastatic melanoma. These gene products have been generated by differential skipping of exons 3 (IL-24 delE3) and 5 (IL-24 delE5). IL-24 delE3 has limited sequence identity to the IL-24-interacting protein mda-7s, and IL-24 delE5 is homologous to IL-24.

Notizen: Murine epidermal cells (EC) act as stimulator cells in the generation of ullogeneic cyto-toxic T lymphocytes (CTL) in cell-mediated lympholysis (CML) and are suitable targets for allogeneic and hapten-self CTL. To analyse the role of EC in the generation of and recognition by ami-self CTL, syngeneic hapten-modified murine EC were used as in vivo and in vitro stimulating populations and as target cells in a hapten-self CML system. Epidermal cells were modified with the sulphydryl-reactive haptenic reagent N-iodoacetyl-N′-(5-sulphonic-l-naphthyl)ethylenediamine (I-AED). C3H.SW (H-2b) AED-self CTL responses were generated by stimulation with syngeneic AED-modified EC and were readily demonstrated when tested on syngeneic hapten-modified EC. These CML responses were hapten-specific and H-2-restricted. No substantial difference was detected in the ability of AED-modified EC and spleen cells (SC) to stimulate the generation of secondary AED-self CTL. Cold target inhibition experiments with hapten-modified EC and SC blockers did not reveal tissue-specific recognition of hapten-modified EC or SC targets by AED-self CTL. These findings demonstrate that hapten-modified EC, when used for priming in vivo and subsequently for in vitro sensitization, can induce hapten-specific self CTL that are reactive against syngeneic hapten-modified EC.

Notizen: Although late recurrence of cutaneous malignant melanoma (CMM) is a known clinical phenomenon, only 12 adequately documented cases exist in the literature. We describe two female patients with CMM who developed melanoma metastases 18 years after radical excision of their primary tumours and presumed cure. Increasing numbers of reports of cases of delayed metastases of CMM might have implications for management and follow up of melanoma patients.

Notizen: Three children with persistent maculopapular and urticarial lesions and vesicles at the predilection sites of dermatitis herpetiformis (DH) were shown to exhibit typical granular, papillary IgA and C3 deposits in the tips of the dermal papillae, as demonstrated by direct immunofluorescence. By immunoelectron microscopy, the IgA deposits were associated with the microfibrils of the elastic fibres as has been described in DH of the adult. C3 deposits were scattered throughout the papillary dermis.Despite the similarity of the clinical appearance, history with regard to gluten sensitive enteropathy (GSE) varied in these three cases. In one child, the skin lesions appeared following faults in the gluten free diet on which he was kept for coeliac disease. Another child developed the skin lesions during a gluten free diet which was not strictly followed; no recurrences of gastrointestinal symptoms accompanied the eruption of DH. In the third case, no evidence for GSE in patient's history or in jejunal biopsies was present at the time of onset of DH.

Notizen: In vivo epiluminescence microscopy (ELM) is a non-invasive technique which improves the clinical diagnosis of naevi and malignant melanoma by providing diagnostic criteria that cannot be appreciated by the naked eye. The present study investigated whether ELM criteria pattern analysis can be employed in an objective, observer-trained, computer-aided diagnostic system, and whether artificial neural networks (ANN) can be applied to the diagnosis of pigmented skin lesions (PSL).The ELM criteria patterns of 200 PSL oil immersion images (60 common naevi, 60 dysplastic naevi, and 80 malignant melanomas) were analysed using a standardized questionnaire. One hundred randomly assigned PSL were used as a training set for an ANN, the remaining 100 PSL serving as the test set. The ANN was trained by backward propagation according to the histological diagnosis, and its performance was compared with that of human investigators.Out of the test set the human investigators correctly diagnosed 88% of PSL and the ANN 86%. in a dichotomized model comparing common, compound, and dysplastic naevi vs. malignant melanoma, i.e. benign vs. malignant PSL, the sensitivity and specificity of human diagnosis was 95 and 90%, respectively, whereas the sensitivity and specificity of the ANN diagnosis was 95 and 88%.Our data indicate that artificial neural networks can be trained to diagnose PSL at a human expert level, based on patterns provided by ELM criteria. We suggest that this technique offers a new approach to the diagnosis of PSL.

Notizen: Background  A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-α2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV.Objectives  The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-α2b were documented.Patients/methods  Twenty-nine male and 18 female patients (mean age 57·6 years, range 34–74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m−2 on days 1–5 orally every 28 days in combination with IFN-α2b 10 MIU m−2 every other day and 27 patients received temozolomide 150 mg m−2 on days 1–5 every 28 days in combination with IFN-α2b in a fixed dose of 10 MIU every other day.Results  We observed an overall response rate of 27·6% comprising five complete remissions (10·6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4·3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6·4%, two patients in group A, one patient in group B). Three patients showed stable disease (6·4%: one patient in group A, two patients in group B). Mean survival was 14·5 months [95% confidence interval (CI) 10–19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P 〈 0·03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30·6 months (95% CI 19·1–42) compared with 25 patients who did not respond (13·7 months 95% CI 9·2–18·3). In total, patients with at least one complete remission showed the longest survival (37·1 months 95% CI 26·3–47·9), followed by patients with at least one partial response (17·4 95% CI 10·9–23·9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths.Conclusions  The combination of temozolomide and IFN-α2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.