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Biomedical subjects

M Landthaler

Publications and source records attributed to M Landthaler.

At least 37 records · Page 2Linked to original sources

Comparison of the 308-nm excimer laser and a 308-nm excimer lamp with 311-nm narrowband ultraviolet B in the treatment of psoriasis.

BACKGROUND: Psoriasis is a chronic, genetically determined inflammatory disease, characterized by an immunomediated pathogenesis, which affects approximately 1-3% of the population. Various modalities have been used for psoriasis treatment, including ultraviolet (UV) radiation. Narrowband UVB (311 nm) phototherapy is a well-established, widely used and highly efficient treatment for psoriasis, but a big disadvantage is that large areas of unaffected skin are irradiated along with the psoriatic lesions. OBJECTIVES: This investigation evaluates a 308-nm excimer laser and a 308-nm excimer lamp in comparison with 311-nm narrowband UVB in the treatment of patch psoriasis by using two different dose-increase schemes. MATERIALS AND METHODS: Fifteen patients with plaque psoriasis were enrolled in the study (first regime). Three different psoriatic lesions were treated with the 308-nm excimer laser, the 308-nm excimer lamp or 311-nm narrowband UVB three times per week. UVB doses were increased slowly and stepwise (1, 1, 2, 2, 3, 3, ...multiple MEDs). Sixteen patients were enrolled in the second regime. Two plaques were treated with the 308-nm excimer laser or with the 308-nm lamp with an accelerated scheme (2, 2, 4, 4, 6, 6, ...multiple MEDs) three times per week. We increased the UVB doses every second treatment (first and second regime) during the whole treatment. If blistering occurred, the blistered plaque was not treated on the next scheduled treatment. At every third visit and 1, 2 and 4 months after the last treatment a Psoriasis Severity Index (PSI) score was assigned in both regimes. RESULTS: Using Friedman analysis, the PSI scores did not show a statistically significant difference (P > 0.05) comparing 308-nm laser therapy, 308-nm lamp therapy and 311-nm narrowband therapy after 10 weeks in the first regime. The mean number of treatments to achieve clearance was 24. With the accelerated scheme, clearance could be achieved with fewer treatments and with half the cumulative dose of the first regime. Nevertheless, the side-effects such as blistering and crusting were also increased. CONCLUSIONS: Both 308-nm light sources can clear patch psoriasis in a similar manner to standard phototherapy, with the advantage of the ability to treat exclusively the affected skin and with a reduced cumulative dose, thus perhaps reducing the long-term risk of carcinogenicity.

Adult↗

Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with severe Moya Moya disease.

A 2-year-old girl with Moya Moya disease who had relapsing cerebrovascular strokes presented with loose skin folds, 'chicken' skin appearance and perforating elastosis serpiginosa-like lesions in the genitocrural region. Histologically, calcified material perforating the epidermis and adjacent short curled and mineralized elastic fibres suggested a variant of pseudoxanthoma elasticum (PXE). As PXE is known to be caused by various mutations in the transmembrane transporter ABCC6 gene, we hypothesized that a novel ABCC6 mutation may underlie this unique combination of PXE and elastopathic vascular damage. Therefore, the complete ABCC6 coding region of the patient and her parents was screened for genetic alterations. No bona fide disease-causing mutation of ABCC6 could be found in the child and in her parents. However, two novel allelic amino acid substitutions (Arg1273Lys and Glu1293Lys; exon 27) were found in the girl and her father, localized in close proximity to the region that codes for the functionally critical second nucleotide-binding fold of ABCC6. Although a causal involvement of these amino acid substitutions could not be proven based on this study, both heterozygote substitutions may possibly have interacted with other undetected recessive maternal ABCC6 changes in the child. To the best of our knowledge, this is the first report of an association between early-onset PXE and severe Moya Moya syndrome possibly related to ABCC6 changes.

Amino Acid Substitution↗

Novel pharmacological approaches in the treatment of psoriasis.

Progress in the understanding of psoriasis as a T-cell mediated inflammatory disease has led to the development of new immunomodulatory therapies. Currently the main focus is on the so-called biologics (or biological agents), including fusion proteins, monoclonal antibodies, cytokines and selective receptors. They mainly target single steps in the complex cascade of humoral and cellular inflammatory immuno-mechanisms that finally lead to the accelerated growth of epidermal and vascular cells in the psoriatic lesions. The most promising and advanced biological agents are discussed along with their influence on the critical pathophysiological steps in psoriasis, including depletion of T cells, blockade of initial T-cell activation and T-cell receptor (TCR) stimulation, blockade of costimulatory signals and T-cell proliferative signals as well as restoration of the T helper type 1 (Th1)/Th2 balance by diminishing type 1 cytokines and administration of type 2 cytokines. In addition to the biological agents, further development of 'classical' dermatological therapies, such as retinoids, or the discovery of new indications for non-dermatological agents contribute to the novel pharmacological approaches in the treatment of psoriasis.

Dermatologic Agents↗

Management of erosive lichen planus with topical tacrolimus and recurrence secondary to metoprolol.

Metoprolol, a widely prescribed beta-adrenergic receptor blocker, has occasionally been associated with a diversity of cutaneous reactions. We present a 79-year-old male patient with erosive lichen planus (LP) on the feet and hands who was successfully treated with topical tacrolimus. Six months after the lesions had been cured the patient received the beta-receptor blocker metoprolol for the treatment of hypertonus. Within only 2 weeks of metoprolol intake the erosive lesions on the palms and feet recurred. After discontinuation of the drug and repetitive topical treatment with tacrolimus a complete remission of the lesions could be achieved. The recurrence of erosive LP probably secondary to metoprolol and the therapeutic success of topical tacrolimus in the treatment of LP are discussed.

Administration, Topical↗

Optimizing treatment parameters for hair removal using long-pulsed Nd:YAG-lasers.

Our aim was to determine the most effective treatment parameters for laser-assisted hair removal using long-pulsed Nd:YAG-lasers. 42 volunteers were treated with 1064 nm long-pulsed Nd:YAG-lasers. We used two different laser systems (Lyra XP, Wavelight and Smartepil II Deka-LMS) with various pulse lengths, fluences, and spot sizes. For each parameter, five test areas were treated one to five times at 4-week intervals. Follow-ups were performed 1, 3, 6, and 12 months after the last treatment. Percentual hair loss, side effects, and pain during treatment were evaluated. The average hair reduction 12 months after the last treatment using the Lyra XP was 48%, using the Smartepil II it ranged between 30% and 35%. There were no permanent side effects. Long-pulsed 1064 nm Nd:YAG-lasers are safe and effective for hair reduction. Although the different treatment parameters did not lead to a lot of differing hair reduction 12 months after the last treatment, the laser with the largest spot size and the longest pulse time showed the best results.

Female↗

[Dialysis associated skin changes].

Patients with end-stage renal disease often suffer from different dermatologic conditions. Reports indicate that 50-100% of patients with end-stage renal disease have at least one cutaneous disorder. The persisting chronic uremia is responsible for a variety of structural and functional skin changes. Dialysis or even renal transplantation leads to an improvement of some uremia associated skin disorders, others however can persist.

Dialysis↗

["Smoldering systemic mastocytosis. "Successful therapy with cladribine].

Mastocytoses are a heterogenous group of diseases characterized by proliferation and accumulation of mast cells in the skin and other organs. They are subdivided into cutaneous mastocytoses; systemic forms, which may appear with or without skin lesions; mast cell sarcomas and extracutaneous, localized, benign mastocytomas. Systemic mastocytoses apart from the skin mainly involve bone marrow, gastrointestinal tract, bones, lymph nodes, spleen and liver. Whereas indolent forms of systemic mastocytosis are mainly treated with antihistamines, glucocorticosteroids and PUVA therapy, the more aggressive forms, including mast cell leukemia, often require cytostatic chemotherapy. A 53-year old patient with beginning "smoldering systemic mastocytosis" failed to respond to high-dose systemic glucocorticosteroids and interferon-alpha. Treatment with cladribine led to an impressive improvement of skin lesions, a significant decrease in tryptase serum levels and stabilization of bone marrow infiltrates.

Antineoplastic Agents↗

Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases.

The heat-shock protein Hsp90 has been shown to be essential for the functional integrity of the telomerase complex. The telomerase activity is enhanced in melanoma and stabilizes the chromosomal integrity in proliferating cells. Furthermore, overexpression of Hsp90 induces silencing of point mutations in transcription factors which, otherwise, would result in a loss-of-function phenotype. In melanocytic lesions there is a higher risk of mutations caused by the enhanced proliferation in melanocytic cells. By analyzing microdissected melanocytic tumors by semiquantitative PCR, we demonstrate an overexpression of Hsp90 mRNA in malignant melanomas (10/14) and in melanoma metastases (6/6) as well as in melanoma cell lines (9/9) when compared with melanocytic nevi (2/9). These results could be confirmed on protein level by immunohistochemistry. While melanocytic nevi show discrete Hsp90 expression only in a minor fraction (2/9), malignant melanomas and metastases show a positive Hsp90 immunohistochemistry in the majority of cases; (7/9) and (13/14), respectively. In addition, by analyzing melanoma metastases by flow cytometry we show that Hsp90 is expressed on the surface of tumor cells (7/8). From these data we conclude that Hsp90 is present in advanced malignant melanomas and may have a stabilizing effect on the cellular functions in proliferating cells of melanocytic lesions and could thereby be a prerequisite for the tumor progression. As Hsp90 is expressed on the cell surface, it might also be a potential immunorelevant target structure for immunotherapy of melanoma.

Biopsy↗

Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts.

BACKGROUND: Recent studies have shown that collagen-degrading matrix metalloproteinase (MMP)-1 and MMP-3 are produced by fibroblasts in response to photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and are considered to be involved in the antisclerotic effects of ALA-PDT observed in the treatment of localized scleroderma. OBJECTIVES: As the primary target of topical PDT is epidermal keratinocytes, we studied the indirect participation of keratinocytes in the production of MMPs and collagen by dermal fibroblasts. METHODS: Keratinocytes were treated with sublethal doses of ALA (100 micromol L(-1)) and red light. The conditioned media were collected 24 h after PDT and primary human fibroblasts were exposed to these media for 6-48 h. Further, a coculture model, keratinocytes seeded on to collagen type IV-coated transwells in the upper chamber and fibroblasts in the lower chamber, was used to study paracrine effects of keratinocytes after PDT. RESULTS: Keratinocyte supernatants after PDT showed a significant, up to 10-fold increase of interleukin (IL)-1alpha and a 2.5-fold increase of tumour necrosis factor-alpha as determined by enzyme-linked immunosorbent assay, while IL-6, MMP-1 and MMP-3 were not altered significantly. Fibroblasts treated with keratinocyte-conditioned media after PDT showed an induction of MMP-1 and MMP-3 protein levels up to threefold in both models used, suggesting that ALA-PDT modulates MMP-1 and MMP-3 production via indirect mechanisms. Collagen type I mRNA expression by fibroblasts was not altered significantly in either model. The addition of an IL-1 receptor antagonist to the keratinocyte-conditioned media completely inhibited the induction of MMP-1 and MMP-3 in stimulated fibroblasts, suggesting that IL-1 is mainly responsible for the observed paracrine effects. CONCLUSIONS: We present evidence that PDT can trigger MMP production in dermal fibroblasts not only directly as has been already shown, but also by an indirect paracrine loop mediated by soluble factors released by epidermal keratinocytes.

Aminolevulinic Acid↗

Role of laser therapy in dermatology -- clinical aspects.

BACKGROUND: Laser therapy has become an integral part of therapeutic alternatives in dermatology. Nevertheless, there are only few statistical data on the role of lasers in everyday practice of dermatological clinics. OBJECTIVE: Analysis of laser patients, indications and lasers used. METHODS: We analysed 10244 patients treated with laser therapy in the Department of Dermatology at the University of Regensburg from 1992 to 2000. This figure represents 9.6 % of all patients seen during that period. RESULTS: Vascular lesions (hemangiomas, port-wine stains, telangiectasias) represented the most common indication (more than 70%) followed by infectious disorders (mostly papillomavirus lesions) as well as the removal of hairs and tattoos. Accordingly, the most frequently used laser was the flashlamp-pumped pulsed dye laser (585 nm) followed by the argon ion, the long-pulse tunable flashlamp-pumped pulsed dye laser, the Q-switch ruby laser, and the CO(2)-laser. In recent years, the percentage of indications and lasers used has changed significantly, reflecting the development of new lasers and the introduction of new indications. CONCLUSIONS: The results confirm the important role of laser therapy in dermatology.

Adolescent↗

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo.

To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamsters were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n=26). PDT was performed (100 mW cm(-2), 100 J cm(-2), continuously or fractionated, and 25 mW cm(-2), 100 J cm(-2); continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20 J cm(-2) for 15 min. Prior to and up to 24 h after PDT tissue, pO(2) was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n=36). Only high-dose PDT resulted in a significant decrease of pO(2). Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO(2). No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.

Aminolevulinic Acid↗

[Actinic keratoses].

Actinic keratoses are defined as proliferation of cytologically atypical keratinocytes in the zone of epidermal-dermal junction in photodamaged skin. In the northern hemisphere the prevalence of actinic keratoses ranges depending on different epidemiological studies from 11% to 25% for people aged 40 or older. The main cause of actinic keratoses is exposure to UVB radiation in sunlight UVB radiation induces mutations in the telomerase gene and in the tumor suppressor gene P53, which can also be detected in invasive squamous cell carcinoma. The only histological parameter to distinguish between actinic keratoses and SCC is the level of invasiveness. The risk for actinic keratoses to develop into SCC is about 16% over lo years. For this reason and because of the high prevalence of actinic keratoses, it has been suggested to replace the term,, actinic keratosis K with intraepidermal squamous cell carcinoma' to better characterize the lesion. In the following review recent aspects of pathogenesis and therapy of actinic keratoses are discussed.

Adult↗

[The dysplastic nevus. Separate entity, melanoma precursor or diagnostic dilemma?].

Today, 20 years after Clark and Elder postulated their tumor progression model of melanocytic lesions from common nevi to melanoma, there are still controversies surrounding this subject. Despite modem molecular biological developments, a consensus about the question, if the dysplastic nevus should be considered as a separate entity, melanoma precursor or just represent a diagnostic dilemma, still seems to be impossible. In addition, since the term melanocytic dysplasia is not precisely defined with regard to all diagnostic methods (clinical morphology, dermatoscopy, dermatopathology, molecular biology), there is considerable confusion. The question remains if a quite arbitrary classification of melanocytic lesions such as dysplastic nevus is useful at all. In daily practice, dermatologists should be aware of the fact that each suspicious melanocytic lesion could represent an early malignant neoplasia, regardless whether it is formally named dysplastic nevus or initial malignant melanoma. We conclude that solid dermatological experience plus novel tools of documentation represent the key factor to minimize patients' risk.

Adult↗

Histopathological diagnosis of onychomycosis by periodic acid-Schiff-stained nail clippings.

BACKGROUND: The current laboratory methods for diagnosing fungal infections of the nails are the potassium hydroxide (KOH) scraping technique and fungal culture. However, due to the long incubation period required for fungal culture and the reported rate of approximately 30% false negative results observed when using these methods, a quick and highly specific screening test for diagnosing onychomycosis is urgently needed. OBJECTIVES: In a prospective study, to compare the traditional mycological diagnostics using culture medium and KOH preparation with the histopathological diagnosis of onychomycosis by periodic acid-Schiff (PAS)-stained nail clippings. METHODS: Material from 387 nails of 350 patients suspected of having onychomycosis was obtained and a KOH stain as well as two fungal cultures (Kimmig agar with and without cycloheximide) were prepared. In addition, the same specimen was histopathologically examined (PAS stain). RESULTS: Culture medium and KOH preparation respectively revealed 100 and 156 cases of onychomycosis, as compared with 182 cases by histological examination. Histological examination gave a significantly higher rate of positive results (P < 0.05). Considering the total number of positive results given by at least one of the three methods (total = 438), histological evaluation was found to give the highest rate of successful recognition of mycotic infection (41.6%). CONCLUSIONS: The histopathological evaluation of PAS-stained nail clippings is very quick and easy to perform, and will increase the frequency of diagnosing onychomycotic disease above that achieved by culture and KOH preparation alone. However, because information concerning the vitality of the fungi and accurate identification of the specific pathogen is not available through this investigation alone, mycological culture continues to remain the indisputable 'gold standard' of mycological diagnostics.

Adolescent↗

Willingness to pay and time trade-off: sensitive to changes of quality of life in psoriasis patients?

BACKGROUND: Willingness to pay (WTP) and time trade-off (TTO) have been used successfully as quality of life (QOL) measurements in dermatology. However, until now there have been no studies available individually comparing these measures pre- and post-treatment. OBJECTIVES: To check sensitivity to changes for WTP and TTO (i). pre- to post-treatment, and (ii). to a 6-month follow-up period. METHODS: We performed a prospective multicentre study in outpatients with psoriasis vulgaris treated with synchronous balneo-phototherapy (simultaneous application of narrowband ultraviolet B and bathing in 10% Dead Sea salt solution). Besides WTP and TTO, the Psoriasis Disability Index (PDI) and the Psoriasis Area and Severity Index (PASI) were monitored. RESULTS: One hundred and ninety-four patients participated in the pretreatment survey, of whom 138 (71%; 84 men, 54 women; mean age 43.9 years) also returned the post-treatment questionnaire. WTP (percentage of monthly income) was shown to be independent of patients' income. During treatment, mean +/- SD WTP fell from 13.8 +/- 19.2% to 11.5 +/- 15.9% (relative improvement 16.7%; P < 0.05), TTO (h per day) from 2.7 +/- 3.8 to 2.3 +/- 3.6 (relative improvement 15%; P < 0.001), PDI improved from 29.8 +/- 18.6 to 23.5 +/- 18.9 (relative improvement 21.1%; P < 0.001) and PASI (available for 113 patients) from 14.9 +/- 7.7 to 5.6 +/- 5.0 (relative improvement 62.4%; P < 0.001). Changes in WTP, PDI and PASI were statistically significantly correlated. Ninety-one of 138 patients (66%) also completed a third survey after a follow-up period: no further changes in PDI, WTP and TTO were found, indicating a stable QOL post-treatment. CONCLUSIONS: Correlation analysis indicated that WTP, assessed as percentage of monthly income, seems to be an appropriate way to measure QOL, unbiased by income of patients. WTP, TTO and PDI were correlated and were sensitive to changes during treatment. WTP and TTO therefore also seem to be appropriate tools for assessment of QOL in interventional studies, especially for pharmacoeconomic analyses.

Absenteeism↗

Long-term dermoscopic follow-up of melanocytic naevi: clinical outcome and patient compliance.

BACKGROUND: Digital dermoscopy for the follow-up of melanocytic naevi (MN) is becoming more common in dermatological private practice. OBJECTIVES: To evaluate the clinical outcome, including the patient's compliance, in a long-term follow-up of single MN. METHODS: Criteria for the selection of MN for follow-up: clinically suspicious without dermoscopically atypical features, or typical for the patient. Clinical outcome measures: number of detected malignant melanomas (MM) and/or atypical MN; quantity, quality, and differences in morphological changes between 'low-risk' patients (no MM in history and < 50 MN) and 'high-risk' patients (MM in history and/or > 50 MN). Compliance: the number of patients who joined a recommended follow-up scheme. RESULTS: No MM was found in 145 consecutive patients (mean age 28 years, 54% female) during a 4-year period (median follow-up per patient: 24 months; ranging 4-45; at least three visits). In five patients (3%), seven histologically proven atypical MN were shown on whole body examination at sites other than those documented. A total of 1968 images in 177 'low-risk' and 95 'high-risk' MN were analysed: 37% (n = 65) of 'low-risk' and 32% (n = 30) of 'high-risk' MN showed dermoscopic changes (difference not statistically significant), none were suspicious for MM. Compliance, evaluated within a separate database of 303 consecutive patients (mean age 32 years, 52% female) over a 6-month period, was only 46%, although recall letters were used. CONCLUSIONS: (i) In our setting of daily routines in dermatological private practices long-term follow-up of a single MN seems not to be helpful for the detection of MM. (ii) A whole body examination must be done at each visit. (iii) The clinician's experience of the type and number of possible morphological changes in MN is crucial in order to avoid unnecessary excisions. (iv) The patient's compliance might be an important problem. (v) Cost-effectiveness has yet to be analysed.

Adult↗