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S Ständer

Publications and source records attributed to S Ständer.

28 records · Page 2Linked to original sources

Hydroxyethyl starch does not cross the blood-brain or the placental barrier but the perineurium of peripheral nerves in infused animals.

Therapy with hydroxyethyl starch (HES) is associated with a high incidence of persistent pruritus due to HES storage in cutaneous nerves. Up to now it has been unknown if HES also accumulates in the extracutaneous peripheral or central nervous system. To study this, five rats including one pregnant one were infused with a single dose (34-150 mg) of HES (70/200/450 kDa molecular weight) conjugated with fluorescein isothiocyanate (FITC). In addition, four sheep were infused with a cumulative dosage of 30 g, 120 g, and 420 g HES (200 kDa), respectively. After 7-13 days, biopsies from the adult rats, four fetal rats and sheep were taken from various organs. The specimens were analyzed by light, electron, and confocal laser scanning microscopy. Typical HES storage vacuoles were found in macrophages of the skin, liver, spleen, lung, and kidney. HES storage in healthy animals was not associated with signs of either inflammation or apoptosis contrary to a previously described animal hemorrhagic shock model. Beyond that, fetus biopsies did not show any storage phenomenon, confirming that HES does not cross the placental barrier. Deposits of HES could be detected in Schwann cells of cutaneous nerve fibers as well as in perineural and endoneural cells of sciatic nerve in one rat (HES 450 kDa) and three of four sheep. No HES storage was found in the central nervous system. Our findings clearly demonstrate that storage of HES is detectable only in small peripheral nerves, suggesting a cutaneous origin of the HES-induced pruritus.

Animals↗

Apoptosis induced by disruption of the actin cytoskeleton is mediated via activation of CD95 (Fas/APO-1).

Activation of the death receptor CD95 by its ligand or by UV radiation is associated with receptor clustering. The mechanism underlying this clustering is mostly unclear. Here we show that although disruption of the actin cytoskeleton by cytochalasin B (CyB) itself induces moderate apoptosis, it enhances apoptosis in HeLa cells induced either by UV radiation or an agonistic anti-CD95 antibody. CyB augments UV-induced apoptosis independently of UV-mediated DNA damage, since induction of DNA repair by exogenous DNA repair enzymes did not alter its enhancing effect. Inhibition of caspase-8, the most upstream caspase in CD95 signaling, blocked the apoptotic effect of CyB and the enhancing effect on UV- and CD95-induced apoptosis. Confocal laser scanning microscopy revealed that (i) CyB induces CD95 clustering, (ii) enhances UV-induced CD95 clustering, and (iii) CD95 clusters colocalize with disrupted actin filaments, suggesting a link between receptor clustering and actin rearrangement. Disruption of CD95 signaling by a dominant negative mutant of the signaling protein FADD protected from CyB-induced apoptosis and prevented the UV-enhancing effect. Accordingly, both the apoptotic and the enhancing effect of CyB was reduced in epidermal cells obtained from CD95 deficient mice (lpr) when compared to wild-type mice. These data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering.

Actins↗

[Familial dyskeratotic comedones. A rare entity].

Familial dyskeratotic comedones is a rare autosomal dominant genodermatosis. In childhood or adolescence disseminated keratotic papules develop and gradually increase in number with time. The isolated papules show a central keratotic plug which tends to recur after extraction. Pruritus and occasional inflammation are the only symptoms. The lesions appear on the extremities, and less frequently on the trunk and the face. About half of the patients have a history of acne vulgaris. The histologic picture is highly characteristic and shows a deep invagination of an acantholytic and dyskeratotic epidermis with prominent cornification. Familial dyskeratotic comedones are generally refractory to any therapy. We report on two sisters with familial dyskeratotic comedones successfully treated by CO2-laser therapy.

Adult↗

[Large melanocytic nevi in generalized atrophic benign epidermolysis bullosa (epidermolysis bullosa nevi)].

Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa. The expression of type XVII collagen (180 kDa bullous pemphigoid antigen) or of laminin 5 is markedly reduced in the skin. A 13-year-old patient with GABEB, developed several large, asymmetric, irregularly pigmented melanocytic nevi with poorly defined borders. They had appeared following blister formation since 8 years of age. Histological examination revealed an irregular proliferation of monomorphous melanocytes at the dermoepidermal junction. Small nests of melanocytes were focally present. This case further emphasizes the difficulty in differentiating nevi appearing in GABEB from malignant melanoma.

Adolescent↗

[Wax model collection of the Department of Dermatology, University of Münster].

Between the 17th century and the middle of the 20th century, wax models were widely used for training in anatomy and other medical fields, especially dermatology. Thereafter, photographic techniques led to the replacement and subsequent dissolution of many European wax model collections. Unfortunately many wax models lose their original colors over time. Since only few mouleurs (wax artists) are still active in Europe conserving wax models, the "dying of moulages" cannot be stopped. Consequently, the existing wax models are of medical and historical interest since they reflect the development of our speciality. The Department of Dermatology in Münster is in the possession of 121 wax models, which are presented in this article.

Dermatology↗

Differential storage of hydroxyethyl starch (HES) in the skin: an immunoelectron-microscopical long-term study.

Hydroxyethyl starch (HES) is widely used as a plasma substitute. Serious side effects occur only rarely, whereas a high incidence of severe pruritus has been reported. Moreover, tissue storage of HES has been demonstrated in various organs. The aim of the current study has been to examine precisely the intracellular uptake and long-term storage of HES in the skin. Skin biopsies from 119 patients who received HES of various preparations and cumulative dosage were obtained 30 min to 130 months after infusion therapy. The samples were analysed by ultrastructural and immunoelectron microscopy with HES-specific monoclonal and polyclonal antibodies. A characteristic vacuolisation of perivascular histiocytes was a regular finding in all skin biopsies as early as 1 day after a single infusion of 30 g. Immunoreactivity for HES was demonstrable within the vacuoles. Generally, the size and number of vacuoles in the histiocytes increased concomitantly with the cumulative dosage. Following administration of higher HES dosages, vacuoles were demonstrable in endothelial cells of blood and lymphatic vessels, basal keratinocytes, epithelia of sweat glands and in small peripheral nerves, the last mentioned being associated with pruritus. A subsequent reduction of the vacuoles in size and number could be demonstrated within 52 months. In nerves, HES deposits persisted no longer than 17 months paralleling the cessation of pruritus. Biopsies taken after 94 months exhibited no HES deposits in the skin. The condensation and final dissolution of the vacuoles may either indicate the release and subsequent redistribution of HES into the circulation or lysosomal degradation.

Adolescent↗

Treatment of prurigo nodularis with topical capsaicin.

BACKGROUND: Prurigo nodularis is an eruption of lichenified or excoriated nodules caused by intractable pruritus that is difficult to treat. Therefore the antipruritic efficacy of capsaicin seemed to be of particular interest because this alkaloid, extractable from red pepper, interferes with the perception of pruritus and pain by depletion of neuropeptides in small sensory cutaneous nerves. OBJECTIVE: The aim of this concentration- and regimen-ranging study was to evaluate the efficacy, safety, and practicability of capsaicin in the topical treatment of prurigo nodularis in a large series of patients. METHODS: A total of 33 patients with prurigo nodularis of various origins were selected to receive capsaicin (0.025% to 0.3%) 4 to 6 times daily for 2 weeks up to 10 months. The consecutive follow-up period was up to 6 months. In 7 patients, skin biopsy specimens were taken before, during, and after therapy and investigated histologically, immunohistochemically, and ultrastructurally. RESULTS: All 33 patients could be evaluated for efficacy. After cessation of the symptoms of neurogenic inflammation, such as burning sensations or erythema, all of them experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to the gradual healing of the skin lesions. After discontinuation of the therapy, pruritus returned in 16 of 33 patients within 2 months. At the ultrastructural level, no degenerative changes of cutaneous nerves could be found during or after capsaicin therapy. Depletion of substance P was demonstrated by confocal laser scanning microscopy thus confirming the specific effect of capsaicin in vivo. CONCLUSION: Topical treatment of prurigo nodularis with capsaicin proved to be an effective and safe regimen resulting in clearing of the skin lesions.

Administration, Topical↗

Terbinafine-induced subacute cutaneous lupus erythematosus.

BACKGROUND: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. OBJECTIVE: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. METHODS: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. RESULTS: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4(1/2) months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. CONCLUSION: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons.

Administration, Oral↗

[Control of section margins without any gaps in paraffin sections of melanoma of the face].

BACKGROUND AND OBJECTIVE: Malignant melanomas on sun-exposed skin are often poorly circumscribed and thus recur frequently. The aim of our clinical trial was to compare conventional to a modified micrographic surgery of primary melanoma. PATIENTS/METHODS: 28 patients with in-situ (n = 7) and invasive (n = 21) melanoma were treated with conventional surgical excision with wide margins; eight of these patients developed a local recurrence. In comparison, 20 patients with primary in-situ (n = 7) and invasive (n = 13) melanoma as well as four patients with recurrence after conventional surgery underwent modified micrographic surgery with delayed closure of the wound. RESULTS: Paraffin specimens of the margins revealed in half of the patients remnants of melanoma although excision was extended to non-lesional skin. Within a mean follow-up period of 21.3 months, none of our patients treated by modified surgery developed a recurrence. CONCLUSIONS: Local recurrencies of melanoma on sun exposed skin may be avoided by means of a modified micrographic surgery using permanent histologic sections.

Adult↗