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Biomedical subjects

W Stolz

Publications and source records attributed to W Stolz.

At least 19 recordsLinked to original sources

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↗

One-year follow-up of a lentigo maligna: first dermoscopic signs of growth.

We report a 64-year-old man with a pigmented lesion on his forehead, initially thought to be actinic lentigo. At follow-up 1 year later the lesion had increased in size and showed new areas of pigmentation. Dermoscopic observation and biopsy led to a diagnosis of lentigo maligna and the lesion was excised. The dermoscopic features indicative of early growth of lentigo maligna are identified and discussed.

Dermoscopy↗

[From the New World. Louis A. Duhring and dermatitis herpetiformis].

Louis Adolphus Duhring (born December 23, 1845) died in Philadelphia, the city of his birth and life work, on May 8, 1913. After medical school, he studied for two years in dermatology departments in London, Paris and Vienna. As a student in Vienna, he was under the tutelage of Ferdinand von Hebra, when the brilliant clinician and teacher was at the zenith of his fame. Duhring's series of 18 papers--published between 1884 and 1891--gave him an important and recognized position as one of the leading dermatological thinkers of the world. These publications described the skin disease which he named "dermatitis herpetiformis" (Duhring's disease). His assertion that dermatitis herpetiformis was a distinct dermatological disease process aroused at first considerable opposition. Moriz Kaposi, at that time the doyen of the Vienna school of dermatology, attacked his views with vigor and tenacity. Louis A. Duhring--this modest, unassuming, quiet-working, gentlemanly physician--made monumental contributions to American dermatology and played a significant role in establishing Philadelphia as one of the great centers of dermatologic activity.

Dermatitis Herpetiformis↗

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↗

Computer assisted learning in medicine: a long-term evaluation of the 'Practical Training Programme Dermatology 2000'.

In recent years, numerous computer assisted learning (CAL) programmes based on new teaching methods, as for example the principles of cognitive apprenticeship and problem based learning, have euphorically been developed for various medical fields. However, many of these programmes failed due to either low acceptance, economic inefficiency, or, most seriously, problems with the implementation and evaluation in medical curricula. In 1999, the practical training course 'Dermatology 2000', an interactive multimedia programme for dermatological education, was developed and completely integrated into the regular dermatological curriculum of five German medical schools. The formative evaluation of an implemented relational database revealed contemporary information about the programme's quantity of use. So far, 3050 students have participated in 6557 lessons. The evaluation of two online questionnaires showed a high learner acceptance regarding the programme's instructional design, ergonomics, and didactical presentation and, after completion of Dermatology 2000, an increased interest in medical education software. A comparison of the objective learning outcome illustrated that Dermatology 2000 students (n = 31) not only outperformed non-participants (n = 7) but also showed a (10%) lower rate of errors in a conventional knowledge test. Additionally, single-case studies demonstrated the increased ability of participating students to apply the acquired knowledge to diagnostic problems. We conclude that the implementation of CAL in present medical curricula can contribute to reformations of medical education. The instructional design of Dermatology 2000 is well accepted and suitable to provide both theoretic biomedical knowledge and clinical skills.

Computer-Assisted Instruction↗

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↗

[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↗

[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↗

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↗

Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG).

In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.

Adolescent↗

Patients with local adverse effects from dental alloys: frequency, complaints, symptoms, allergy.

Data on the prevalence of adverse effects from dental cast alloys and on the characteristics of the related patient groups are scarce. Therefore, the aim of the present study was to investigate patients in a defined part of Germany attributing oral complaints or symptoms to dental cast alloys. All dentists in the area of Eastern Bavaria (with 1 million inhabitants) were asked to send corresponding patients to our department during a 3-year period. Out of this collection, patients with complaints or symptoms in the oral cavity were recruited and characterized with regard to number, age and sex distribution, type of subjective complaints and objective intraoral symptoms, and allergy status based on an alloy analysis. Patients reporting to our department with suspected local adverse effects from dental cast alloys represented 0.01% of the population. Thirty-four percent of the patients were 50-59 years old, with females prevailing (76%). A great variety of subjective complaints was reported, which mainly resembles those reported by patients with adverse effects attributed to other dental materials like amalgam or denture base materials. The main objective intraoral symptoms were gingivitis, anomalies of the tongue (lingua plicata, lingua geographica), discoloration of the gingiva, redness of the palate or tongue and lichenoid reactions of the oral mucosa. In not more than 10% of the patients, allergy was diagnosed as contributing to the complaints or symptoms.

Adult↗

Dermatoscopy of lentigo maligna.

Lentigo maligna and LMM require different dermatoscopic criteria for evaluation. The ease and accessibility of examining these lesions with dermatoscopy coupled with the clinical pathologic correlation afforded by the biopsy techniques discussed allow the practitioner to become proficient and prescient with the use of dermatoscopy. The criteria mentioned here are relatively new but are present and detectable in most cases of LM and LMM. The fact that there is some overlap among pigmented actinic keratosis, squamous cell carcinoma in situ, and lichenoid keratosis lesions should not detract or deter the physician from using dermatoscopy. Clinically, these lesions also usually will be equivocal and will require close clinical scrutiny and biopsies. If given the choice of using skin surface microscopy for one class of lesion only, one might well choose LM lesions because of their otherwise subtle nature and the clues that can be unlocked with oil immersion, illumination, and magnification, along with knowledge of these new criteria.

Dermatology↗