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Biomedical subjects

M Meurer

Publications and source records attributed to M Meurer.

At least 37 records · Page 2Linked to original sources

[Topical treatment of psoriasis: a systematic update].

Classical topical treatment regimens in psoriasis including dithranol and corticosteroids are widely used and have been supplemented in recent years by topical vitamin D preparations, by vitamin D analogues and topical retinoids. The combination of these preparations with each other, with UV light or with systemic drugs often lead to improved effectiveness and tolerability when compared with the respective monotherapy. In private offices, the combination of calcipotriol with various corticosteroids is very commonly prescribed for patients with mild to moderate psoriasis. This combination can be sequentially applied twice daily or--in a newly introduced fixed preparation--once daily. In severe psoriasis requiring systemic treatment a concomitant effective topical treatment regimen can greatly improve the overall longtime management in affected patients.

Administration, Topical↗

The emigration of Germany's Jewish dermatologists in the period of National Socialism.

In the context of our investigation, we found information on 432 (76%) of the 569 Jewish dermatologists in Germany. There is evidence that 57 (10%) of the Jewish dermatologists were murdered in concentration camps, 61 (10.7%) died a natural death, 13 (2%) committed suicide, and 25 (4%) survived the Third Reich in Germany. After 1933, 276 (49%) Jewish dermatologists were able to leave Germany; the United States of America was the main destination and 107 (or 41%) emigrated there. A total of 34 (13%) Jewish dermatologists emigrated from Germany to Palestine and 16 to Latin America. Regarding emigration to other European countries, 20 of the Jewish dermatologists from Germany went to Great Britain (including Walter Freudenthal, 1893-1952, and Ernst Sklarz, 1894-1975), and 24 emigrated to other European countries, such as France (Rudolf Mayer, 1895-1962), Sweden (Carl Lennhoff, 1883-1963), and the Netherlands (Otto Schlein, 1895-1944).

Dermatology↗

[Initial scleromyxedema. Successful treatment with melphalan].

Scleromyxedema is a rare mucinous disease without thyroid dysfunction, associated with a monoclonal gammopathy. The deposits of mucin in the skin and other organs such as the cardiovasculary system, determine the prognosis of the disease. A 74-year old patient with initial scleromyxedema is described, in whom a pulse therapy with melphalan was initiated already in the early stages of the disease. Four cycles of melphalan in combination with prednisolon led to a complete and sofar stable remission of the disease.

Aged↗

[Multiple miliary osteomas of the face].

Osteoma cutis is a single or multiple ectope calcification with development of bony structures in the skin. We distinguish between primary and secondary ossification. Multiple miliary osteoma in the face has mostly been described secondary to preexisting acne vulgaris. We present a 62-year-old woman who developed multiple miliary osteoma in the face together with repeated doses of estrogen and discuss pathogenesis and therapeutic possibilities.

Biopsy↗

Dynamic susceptibility contrast-enhanced echo-planar imaging of cerebral gliomas. Effect of contrast medium extravasation.

PURPOSE: To assess the influence of the degree of contrast medium extravasation on different DSC EPI MR sequences for perfusion MR imaging. MATERIAL AND METHODS: 60 patients with cerebral gliomas were examined by either an FID EPI or an SE EPI DSC MR sequence. The acquired images were evaluated on a qualitative and quantitative basis. For qualitative assessment, the homogeneity of the signal time curve, image artifacts, the degree of signal drop and the degree of enhancement were evaluated. The quantitative assessment included the percentage of signal drop and the contrast-to-noise ratio of the different EPI sequences was analyzed. RESULTS: FID EPI presented a more homogeneous signal time curve and a more pronounced susceptibility effect than the SE EPI sequence. Due to the lesser susceptibility effect, the SE EPI sequence was not as sensitive to contrast media extravasation. The signal returned to baseline in all patients. In patients with strongly enhancing lesions, the FID EPI sequence suffered from considerable T1 effects, causing problems in the quantification of perfusion data. CONCLUSION: FID EPI sequences were preferred for perfusion MR imaging in patients without strong enhancing lesions, e.g. in ischemia or tumors with intact blood-brain barrier. In patients with suspected strong enhancing lesions, an SE EPI sequence should be used.

Brain Neoplasms↗

[Pemphigus vegetans. A historical perspective].

Pemphigus vegetans is a rare variant of pemphigus which is mainly localized in the intertriginous areas (Neumann type, Hallopeau type) or primarily involves the mucous membranes (pyostomatitis vegetans). A 18-year-old patient with erosive stomatitis developed a vegetating plaque with papillomatous and verruciform features in her left axilla. Histopathological examination of the axilla revealed papillomatosis and acanthosis as well as suprabasal clefting with acantholytic cells. By direct immunofluorescent examination, deposits of immunoglobulin IgG and complement (C3) were found in the intercellular space of the epidermis. Serological examination by indirect immunofluorescent techniques was indicative of pemphigus autoantibodies at a titer of 1:40. This case report demonstrates that the classical differentiation of pemphigus vegetans in two types, Neumann type and Hallopeau type, is mainly of historical importance, because both entities may represent variants of the same disease. In addition, other disorders such as IgA pemphigus may also present with vegetating plaques in intertriginous sites.

Adolescent↗

UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model.

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol (1alpha,25-dihydroxyvitamin D3). This study was initiated to test whether the ultraviolet-B-induced photolysis of provitamin D3 (7-dehydrocholesterol), which results in the formation of vitamin D3, can generate calcitriol in an in vivo-like human skin equivalent model made of fibroblasts in a collagen matrix as the dermal component and keratinocytes as the epidermal component. Cultures were preincubated with increasing concentrations of 7-dehydrocholesterol (0.53-5.94 nmol per cm2 human skin equivalent) at 37 degrees C and irradiated with monochromatic ultraviolet B at wavelengths ranging from 285 to 315 nm (effective ultraviolet doses 7.5-45 mJ per cm2). In our in vitro model irradiation with ultraviolet B resulted in a sequential metabolic process with generation of previtamin D3 followed by the time-dependent formation of vitamin D3, 25-hydroxyvitamin D3, and ultimately calcitriol in the femtomolar range. Unirradiated cultures and irradiated cultures without keratinocytes generated no calcitriol. Irradiation of skin equivalents at wavelengths > 315 nm generated no or only trace amounts of calcitriol. The ultraviolet-B-triggered conversion of 7-dehydrocholesterol to calcitriol was strongly inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases. The amount of calcitriol generated was dependent on the 7-dehydrocholesterol concentration, on wavelength, and on ultraviolet B dose. Hence, keratinocytes in the presence of physiologic concentrations of 7-dehydrocholesterol and irradiated with therapeutic doses of ultraviolet B may be a potential source of biologically active calcitriol within the epidermis.

Cholecalciferol↗

Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.

AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

Adult↗

Conversion of vitamin D3 to 1alpha,25-dihydroxyvitamin D3 in human skin equivalents.

These results demonstrate for the first time that human keratinocytes under in vivo-like conditions have the capacity of the enzymatic hydroxylation of vitamin D3 to hormonally active calcitriol (1alpha,25(OH)2D3). Supplementation of the culture medium with bovine serum albumin (BSA) up to 1.5%) (w/v) amplifies the conversion of vitamin D3 to 1alpha,25(OH)2D3. The maximum turnover rate of this reaction at 780 nM vitamin D3 in presence of 1.0% (w/v) BSA amounts to approximately 3 pmol 1alpha,25(OH)2D3 per 10(6) cells after 6 h of incubation. The hydroxylation of vitamin D3 to 1alpha,25(OH)2D3 is inhibited by the P-450 oxidase inhibitor ketoconazole. The generation of 1alpha,25(OH)2D3 from vitamin D3 has an apparent Michaelis constant (Km) of 2.3x10(-6) M. The intrinsic conversion of vitamin D3 to biologically active 1alpha,25(OH)2D3 may be of importance for the regulation of proliferation and differentiation of keratinocytes.

Cells, Cultured↗

Clinical and immunologic parameters during thalidomide treatment of lupus erythematosus.

BACKGROUND: Thalidomide is used as an experimental drug for the treatment of chronic inflammatory diseases with an autoimmune or infectious background. The pharmacologic action involves the downregulation of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis; however, not much is known about thalidomide's effect on immunologic parameters in lupus erythematosus (LE). Method This is an open study of a group of five consecutive systemic lupus erythematosus (SLE) patients treated with thalidomide (100 mg/day) and five consecutive cutaneous LE patients not responsive to conventional therapy. The clinical and immunologic parameters (C-reactive protein, immunoglobulin, and complement serum levels, lymphocyte counts) were investigated during thalidomide treatment for up to 2 years in both patient groups. RESULTS: An increase in the absolute peripheral lymphocyte count was observed beginning after 2 weeks of systemic thalidomide treatment in nine out of 10 LE patients, and remained stable throughout thalidomide treatment. Elevated serum levels of C-reactive protein and titers of autoantibodies to double-stranded (ds) DNA decreased in SLE patients. No significant changes were detected in the serum levels of the complement components C3 and C4 and immunoglobulins in all LE patients. Regression of inflammatory skin lesions and regrowth of hair were recorded. As a side-effect, polyneuropathy was observed in four out of 10 patients, with the earliest onset at 3 weeks of thalidomide treatment. CONCLUSIONS: Thalidomide is a potent anti-inflammatory drug in patients with SLE and cutaneous LE, possibly interacting with the recruitment of lymphocytes. It leads to the regrowth of hair in LE-related alopecia and effluvium. Early symptoms of polyneuropathy should be registered and the drug should be withdrawn. Thalidomide should be restricted to patients who show no response to standard therapeutic regimens and should only be used under strict precautions with regard to its known teratogenic risk.

Adult↗

A novel pathway for hormonally active calcitriol.

Calcitriol [1alpha,25(OH)2D3], the hormonally active form of vitamin D3 (D3) is produced in both renal and extrarenal tissues. Our findings demonstrate that physiological doses of UVB radiation at 300 nm induce the conversion of 7-dehydrocholesterol (7-DHC) via preD3 and D3 into calcitriol in the pmol range in epidermal keratinocytes. The hydroxylation of photosynthesized D3 to calcitriol is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450 mixed function oxidases. The UVB-induced formation of calcitriol in human skin is demonstrable in vivo by the microdialysis technique. These results suggest that human skin is an autonomous source of hormonally active calcitriol.

Calcitriol↗

UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in the human keratinocyte line HaCaT.

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol. The present study was initiated to test whether ultraviolet B (UVB)-induced photolysis of provitamin D3 (7-dehydrocholesterol, [7-DHC]) which results in the formation of vitamin D3 also leads to the generation of calcitriol in keratinocytes. Submerged monolayers of HaCaT keratinocytes were preincubated with 7-DHC (25 microM) at 37 degrees C and irradiated with monochromatic UVB at different wavelengths (effective UV-doses: 7.5-60 mJ/cm2), or a narrow-band fluorescent lamp Philips TL-01 (UVB-doses: 125-1500 mJ/cm2). Irradiation with both sources of UVB resulted in the generation of different amounts of previtamin D3 in our in vitro model followed by time-dependent isomerization to vitamin D3 and consecutive formation of calcitriol in the picomolar range. Unirradiated cultures or cultures exposed to wavelengths > 315 nm generated no or only trace amounts of calcitriol. The conversion of vitamin D3 generated after UVB irradiation to calcitriol is inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases in this chemical reaction. The generation of calcitriol was wavelength- and UVB dose dependent and reached approximately 18-fold higher levels after irradiation at 297 nm than at 310 nm (effective UVB dose: 30 mJ/cm2). Hence, keratinocytes may be a potential source of biologically active calcitriol within epidermis, when irradiated with therapeutical doses of UVB.

Calcitriol↗

Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents--a preliminary study.

The presence of both 1alpha-hydroxylase activity and 25-hydroxylase activity is a biochemical prerequisite for the enzymatic generation of 1alpha,25(OH)2D3 from vitamin D3 in keratinocytes. In contrast to 1alpha-hydroxylase, however, activity of a 25-hydroxylase in keratinocytes has not previously been demonstrated. In this study, using RT-PCR we detected vitamin D3 25-hydroxylase mRNA in human keratinocytes. The expression of vitamin D3 25-hydroxylase mRNA in keratinocytes was identical to that of CYP27 expressed in mitochondria of human hepatoma HepG2 cells. CYP27 mRNA in keratinocytes is not constitutively expressed but is inducible both by vitamin D3 (780 nM) and by UVB radiation (300 nm, 30 mJ/cm2).

Carcinoma, Hepatocellular↗

Paraneoplastic pemphigus with fatal pulmonary involvement in a woman with a mesenteric Castleman tumour.

A 42-year-old woman presented with oral and labial erosions, conjunctivitis, facial rash and lichenoid erythematous papules on the trunk. Paraneoplastic pemphigus (PNP) was suspected, and a search for a neoplasm revealed an intra-abdominal Castleman tumour sized 7 x 5 x 6 cm. After removal of the Castleman tumour, the skin and mucosal inflammation gradually subsided over the next 12 months. However, due to irreversible pulmonary involvement the patient died of intractable respiratory distress 2 years after the onset of the disease. Systemic corticosteroids, azathioprine, cyclophosphamide, high-dose intravenous immunoglobulins and thalidomide were ineffective. The diagnosis of PNP was confirmed by keratinocyte antigen immunoprecipitation with the patient's serum.

Adult↗