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M Landthaler

Publications and source records attributed to M Landthaler.

At least 55 records · Page 3Linked to original sources
PubMed2003

Identification of differentially expressed genes in models of melanoma progression by cDNA array analysis: SPARC, MIF and a novel cathepsin protease characterize aggressive phenotypes.

Currently, the scale and consistency of changes of gene expression profiles in models of melanoma progression are largely unknown. Therefore, we investigated siblings of cell lines or malignant melanomas (MM), which have been selected by nude mouse passages for (a). increased tumorigenicity (local ECM-independent growth), (b). metastatic potential, or (c). selected for increase invasiveness using the Boyden chamber. cDNA array analysis surveying more than 27.000 transcripts per cell line showed that 1.5-2.8% of all detectable transcripts were consistently differentially regulated during selection process in those models. Using array analysis, we identified 33 individual transcripts that exhibited significant differential hybridization paralleling the increased aggressiveness of the selected progeny. Because some of those genes could play a significant functional role in the progression of MM, we additionally proved their regulative pattern using Northern blotting. Among others, progressive overexpression of osteonectin/SPARC, a angiogenesis, was found in the selected offspring from all three experimental models and may therefore be considered as a potential marker for aggressive MM as well a promising therapeutic target. We further show that the selection of MM cells for increased ECM-independent local growth was accompanied by overexpresssion of macrophage migration inhibiting factor (MIF), an important modulator of both cell cycle progression and angiogenesis, and cathepsin Z, a novel member of the family of matrix degrading proteinases.

Animals↗
PubMed2002

[Cutaneous microdialysis. Use in dermatology].

The determination of concentrations of exogenous or endogenous substances in the dermis, e.g. for pharmacokinetic studies, is technically difficult. Performing skin biopsies or inducing suction blisters results in the disintegration of the tissue and allows only single measurements. Recently, cutaneous microdialysis, a new simple and minimally invasive technique for continuously measuring of substances in the dermis in vivo, has been introduced in dermatological research. According to the principle of dialysis, a semipermeable membrane is inserted in the dermis and due to a concentration gradient between the interstitial space and a perfusate, substances diffuse through the pores of the membrane and can be analyzed in the dialysate. Cutaneous microdialysis represents a useful technique for pharmacokinetic or pharmacodynamic studies as well as for investigations regarding cutaneous physiology and pathophysiology.

Biological Availability↗
PubMed2002

[Psoriatic onycho-pachydermo- periostitis].

We report about a patient with a 2 year history of palmo-plantar psoriasis and psoriatic involvement of the nails. Within six months he developed a psoriatic onychodystrophy and painful swellings of the toes and fingers. X-rays revealed acral lamellar periostitis. The case of this patient represents a rare variety of psoriatic arthritis: The psoriatic onycho-pachydermo-periostitis. After a 6 week therapy with methotrexate (15mg per week) the nails began to grow regularly. Therefore, in cases of psoriasis with unusual symptoms of psoriatic arthritis the psoriatic onycho-pachydermo-periostitis should be included in differential diagnosis and therapy.

Adult↗
PubMed2002

Correlations between light penetration into skin and the therapeutic outcome following laser therapy of port-wine stains.

For several years the flashlamp-pumped pulsed dye laser (FPDL) has been the favoured method for the treatment of port-wine stains (PWS). The therapeutic outcome of FPDL laser therapy depends on the anatomical location of the PWS and is mainly attributed to morphological parameters such as size and depth of the PWS blood vessels. The aim of this study was to show a correlation between the therapeutic outcome following FPDL therapy and the optical properties of the skin overlying the PWS vessels. For this purpose the therapeutic outcome following FPDL treatment (585 nm; 0.45 ms) of 884 PWS situated on different body sites was evaluated by judging the grade of fading of PWS colour. On the other hand the light penetration into 123 skin samples (thickness 0.10-1.35 mm) was determined between 450 nm and 1030 nm and compared with the PWS laser therapy outcome for equal locations by statistical analysis. PWS on the neck, trunk, arms or legs yielded a higher mean grade of fading as compared to PWS on the head. Within the face, a wide range of fading was evident. The light penetration into skin increased linearly with increasing wavelength and location-dependent differences were found. The attenuation coefficient was 22.8+/-5.3 mm(-1) at 585 nm. No significant or strong correlation was observed between the therapeutic outcome of PWS laser therapy and the light penetration into skin. However, a correlation was obvious by plotting the respective profile plots. Therefore, among other effects, in particular morphological parameters of PWS vessels, the optical properties of the skin contribute to a small extent to the clinical outcome of PWS laser therapy.

Adolescent↗
PubMed2002

[How large is the loss of effectiveness of a treatment procedure between "theory" and "practice"? Evaluating health economics basic data within the scope of a trial model of ambulatory synchronous balenophototherapy of atopic eczema].

BACKGROUND AND OBJECTIVE: Before introducing new treatment modalities, efficacy has to be proven in clinical trials. Furthermore, it is of special interest to what extent results of clinical trials can be transferred to daily routine. PATIENTS/METHODS: In the framework of a trial on out-patient synchronous balneophototherapy, a possible loss in treatment efficacy from "clinical trial" to "daily routine" was examined. Therefore all patients without protocol deviations (representing treatment success available in a "clinical trial") and all patients with at least one treatment session regardless of protocol deviations (model for "daily routine") were analyzed. RESULTS: 257 "daily routine" and 1281 "clinical trial" patients with atopic dermatitis were analyzed. Relative SCORAD-improvements provided a clear loss in treatment efficacy in the "daily routine" group of 14.2%: 55% of patients received less than the planned 3 treatments per week and 48% left the study early because of noncompliance, good improvement, lack of time or lack of efficacy. CONCLUSIONS: For the first time a loss of efficacy of a treatment modality between "theory" and "practice" can be demonstrated in a representative number of patients suffering from atopic dermatitis. For the optimal use of rare financial resources, the comparison of different treatment modalities under "daily routine" conditions is also necessary in future.

Adult↗
PubMed2002

Willingness to pay and time trade-off: useful utility indicators for the assessment of quality of life and patient satisfaction in patients with port wine stains.

BACKGROUND: For cost utility analyses in health economic research it is necessary to assess quality of life for content validation. Previously, both quality of life questionnaires and utility indicators such as willingness to pay and time trade-off have been used successfully in patients with chronic skin diseases, such as psoriasis vulgaris or atopic eczema. OBJECTIVE: For the first time to assess willingness to pay and time trade-off in patients with port wine stains, and to study possible correlations between these indicators, patient income, quality of life questionnaires and subjective or objective outcome measures. METHODS: The results of a survey on 36 patients with facial lesions who had completed laser treatment were used for assessments. The 'Chronic Skin Disease Questionnaire' (CSDQ) and the 'Short Form-36 Health Survey' (SF-36) were used as quality of life questionnaires. Special questions were used as a basis for calculating the utility indicators, willingness to pay and time trade-off. RESULTS: Completed questionnaires were sent back by 25 patients (69%). Willingness to pay and time trade-off were used as instruments for the assessment of quality of life [questions answered by 23 (92% of respondents)]; patients were willing to pay 11.8% of their monthly income and would offer a mean value of 1.2 h per day for an imaginary therapy leading to complete cure of the skin problem. Statistical correlation analyses were not performed because this pilot study included only a small number of patients. Frequency distributions show no apparent correlation between willingness to pay and patients' profession (used as a surrogate for income). Possible correlations were seen between willingness to pay, time trade-off, the scales 'anxiety/avoidance' and 'helplessness' of the CSDQ as well as 'social function' of SF-36 and subjective or objective efficacy. Twenty-nine patients (80%) were willing to pay for the treatment, a surrogate measure for patients' satisfaction with treatment modality. Overall, patients would pay an average of 16.0 euros per single treatment and 192.0 euros for the whole course of treatments. In contrast with patients who evaluated treatment modality as excellent or very good (willingness to pay for single treatment, euro 22.0; for whole treatment, 270.0 euros), patients who judged treatment good (8.0 euros, 145.0 euros), moderate or bad (12.0 euros, 146 .0 euros) were willing to pay markedly less. CONCLUSIONS: (i) The questions for willingness to pay and time trade-off were understood by most patients and produced meaningful answers. (ii) There were apparent correlations between the utility indicators, subjective or objective outcome and the scales of the quality of life questionnaires. (iii) The results show that these indicators have a high potential for use in this dermatological condition, especially as a basis for health economic evaluations.

Adult↗
PubMed2002

Non-oncologic indications for ALA-PDT.

Topical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a well-established treatment regimen for superficial epithelial skin tumours, but it is evident that inflammatory diseases of the skin and virus-induced lesions can also profit from PDT. Depending on the light dose applied, either cytotoxic effects resulting in tumour destruction or immunomodulatory effects resulting in improvement of inflammatory conditions occur. Patients with localized scleroderma that had been unresponsive to various treatments, including PUVA or bath-PUVA therapy, respond very well to topical ALA-PDT performed repeatedly. In contrast to PUVA therapy, no carcinogenic potential is being discussed for PDT. Also, HPV-induced skin lesions might provide a possible indication for topical ALA-PDT. The rapidly proliferating cells in viral acanthomas accumulate ALA-induced protoporphyrin IX (PPIX) selectively when compared to the surrounding non-infected cells. The efficacy of topical ALA-PDT in the treatment of recalcitrant foot and hand warts has been shown in a placebo-controlled, randomized, double-blind trial. Furthermore, case reports describe a good response of other virus-induced diseases, for example condylomata acuminata and epidermodysplasia verruciformis, to topical PDT with ALA. However, controlled clinical trials are still needed to demonstrate more fully the effectiveness of PDT for inflammatory skin diseases.

Aminolevulinic Acid↗
PubMed2001

[Paraneoplastic Bazex acrokeratosis in adenocarcinoma of the stomach].

HISTORY AND EXAMINATION: A 58-year-old man presented with a sudden eruption of hyperkeratoses on hands and feet. Alcohol abuse had been present 10 years ago, together with a gastric ulcer. Physical examination was unremarkable, except for plantar bizarre hyperkeratoses especially at the sides of the feet as well as some rhagades with spread to the dorsum of the toes. Similar but less severe hyperkeratoses were found on the palms. INVESTIGATIONS: Laboratory investigation was essentially normal. X-rays of the thorax and sinuses as well as a sonography of the stomach revealed, except for a fatty liver, no pathological findings. Gastroscopy revealed a chronic active gastritis on the small curvature of the stomach. Only a second gastroscopy and biopsy revealed an adenocarcinoma of the stomach. DIAGNOSIS, THERAPY AND COURSE: According to the clinical presentation a paraneoplastic acrokeratosis (Bazex syndrome) was diagnosed. The patient was given high-dose chemotherapy with subsequent stem-cell transplantation and gastrectomy. The skin problems resolved after the first cycles of chemotherapy. CONCLUSION: If clinically a paraneoplastic acrokeratosis is suspected extensive search for a malignancy has to be initiated, including a gastroscopy, because rarely, but as in the present case, a carcinoma of the stomach can be the underlying cause.

Adenocarcinoma↗
PubMed2001

Laser surgical planning with magnetic resonance imaging-based 3-dimensional reconstructions for intralesional Nd:YAG laser therapy of a venous malformation of the neck.

BACKGROUND: Three-dimensional (3-D) imaging using computed tomography or magnetic resonance imaging data is well known for surgical planning of complex lesions in neurosurgery. In dermatology, percutaneous and intralesional Nd:YAG laser therapy is well established for numerous types of vascular malformations. Diagnostic imaging using ultrasound, computed tomography, or magnetic resonance imaging is necessary to plan the laser therapy of those malformations. The therapeutic problem is to localize the venous malformation exactly before treatment on sectional 2-dimensional images. OBSERVATIONS: We describe a 27-year-old woman with a venous malformation of the neck. The data of diagnostic magnetic resonance imaging were used for a 3-D reconstruction of the venous malformation to demonstrate the anatomical extent and subcutaneous involvement for laser surgical planning. Percutaneous and intralesional laser therapy was performed at 3-month intervals with the Nd:YAG laser using the 3-D reconstruction as a road map for the Nd:YAG laser. Eight weeks after the last laser treatment, the bulky lesions of the neck showed regression. Using the 3-D reconstruction for laser surgical planning, physicians could perform intralesional laser treatment more exactly. The complex anatomy of the venous malformation could be elucidated by studying the 3-D images before and during laser surgery. CONCLUSION: The use of magnetic resonance imaging-based 3-D reconstructions for laser surgical planning can demonstrate the often unexpected extent and improve the intralesional laser therapy in the treatment of venous malformations.

Adult↗
PubMed2001

Overexpression of monocyte chemoattractant protein 1 in systemic sclerosis: role of platelet-derived growth factor and effects on monocyte chemotaxis and collagen synthesis.

OBJECTIVE: In addition to its chemotactic properties, recent evidence suggests that monocyte chemoattractant protein 1 (MCP-1) might participate in the fibrotic process by inducing the secretion of extracellular matrix (ECM) components. Since the factors that initiate the accumulation of inflammatory infiltrates and ECM deposits in systemic sclerosis (SSc) skin lesions are still unknown, this study was undertaken to examine the role of MCP-1 in SSc. METHODS: In situ hybridization and immunohistochemistry studies for MCP-1 were performed on skin biopsy specimens from patients with SSc and healthy controls. To identify possible stimulators of MCP-1 overexpression in SSc lesions, cultured dermal fibroblasts were incubated with recombinant platelet-derived growth factor (PDGF) and analyzed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. The chemotactic effects of SSc fibroblasts were examined using a modified Boyden chamber assay. To analyze the fibrotic potential of MCP-1, cultured dermal fibroblasts were incubated with recombinant MCP-1, and type I procollagen was measured by radioimmunoassay and real-time PCR. RESULTS: MCP-1 was expressed by fibroblasts, keratinocytes, and perivascular infiltrates throughout the skin, in involved as well as uninvolved skin areas, from 10 of 11 SSc patients, whereas no expression of MCP-1 was found in healthy controls. Stimulation with PDGF resulted in a significant increase in MCP-1 messenger RNA and protein, with differences between healthy control fibroblasts and fibroblasts from SSc patients. The chemotactic activity for peripheral blood mononuclear cells of SSc fibroblast supernatants increased in a time-dependent manner. Antibodies blocking MCP-1 decreased the chemotactic activity of SSc fibroblasts by a mean +/- SD of 37 +/- 12%. Despite an increase in type I collagen levels over time, no effect of recombinant MCP-1 on the synthesis of type I collagen was observed. CONCLUSION: These data indicate that MCP-1 might contribute to the initiation of inflammatory infiltrates in SSc. Possible stimuli of MCP-1 in dermal SSc lesions include PDGF, which is known to be expressed in SSc. In contrast to previous findings in fibrotic lung diseases, no effect of MCP-1 on collagen synthesis was observed in SSc dermal fibroblasts in vitro.

Becaplermin↗
PubMed2001

Long-term results in the treatment of childhood hemangioma with the flashlamp-pumped pulsed dye laser: an evaluation of 617 cases.

BACKGROUND AND OBJECTIVE: Presenting the long-term results of flashlamp-pumped pulsed dye laser treatment in 617 hemangiomas to evaluate this treatment modality. STUDY DESIGN/MATERIALS AND METHODS: In 548 children, 692 hemangiomas were treated with the flashlamp-pumped pulsed dye laser (FPDL) SPTL 1B (Candela Corporation, Wayland, MA). The objective of treatment was the inhibition of further growth or the induction of regression. The treatment results were documented by the treating physician as well as by means of a questionnaire delivered to the parents. A total of 617 treatment results could be evaluated. RESULTS: After 1--12 treatments (mean, 2.5), we could achieve our treatment objective to stop the further growth of the lesion in 96.6% of all hemangiomas. In 13.8%, the treatment resulted in a complete remission, a significant regression was seen in 14.9%, and 67.9% of the treated lesions showed a discontinuation of growth. The percentage of complete remission was especially high in small superficial (42.6%) and superficial (19%) hemangiomas. CONCLUSION: In the vast majority of the hemangiomas, it was possible to stop further progression or induce regression by FPDL treatment. Total regression could be achieved in nearly half of the small superficial hemangiomas. Because the treatment is fast, effective, and nearly without side effects, we recommend early laser treatment especially in superficial and small childhood hemangiomas.

Age Factors↗
PubMed2001

Melanoma inhibitory activity (MIA), a serological marker of malignant melanoma.

Melanoma inhibitory activity (MIA) was originally identified as an 11 kDa protein secreted from malignant melanoma cells. We have shown that MIA is strongly expressed in melanoma and melanoma cell lines but not in melanocytes and normal skin. We also observed that MIA mRNA expression correlates with progressive malignancy of melanocytic tumors. Measuring MIA in serum or plasma by a sensitive and quantitative ELISA and investigating the potential of MIA serum levels as a novel marker for malignant melanomas showed that the protein can be used to monitor therapy and follow-up. The present study measured the variations in blood concentrations of MIA in 84 patients with stage II-IV melanoma by ELISA. Patients treated with repeated injections of a polyvalent melanoma vaccine (PMV), interferon-alpha-2b (IFN-alpha 2b) or interleukin-2 (IL-2) were followed during treatment duration. Before treatment, patients treated with PMV or IFN-alpha 2b had comparable low MIA concentrations, whereas most IL-2-treated patients had higher MIA levels. At the end of treatment, MIA concentrations were higher in patients with progressive disease (PD) than in patients with no clinical evidence of melanoma (NPD) for PMV, IFN-alpha 2b or IL-2 therapy (3.7 +/- 0.2 vs 11.5 +/- 5.4 ng/ml, 3.8 +/- 0.2 vs 8.3 +/- 1.7 ng/ml, and 2.3 +/- 0.7 vs 20.2 +/- 7.4 ng/ml, respectively, p < 0.05). In contrast to the stable MIA concentrations measured in NPD patients, significant increase in MIA levels were observed in PD patients over time regardless of treatment. For PMV- and IFN-alpha 2b-treated patients, a rise in MIA levels occurred significantly earlier than clinical diagnosis of melanoma recurrence. In conclusion, our data suggest that quantitation of MIA serum levels may be used for detection of both clinically apparent and non-apparent metastatic melanoma disease and for monitoring therapy.

Animals↗