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Andreas Blum

Publications and source records attributed to Andreas Blum.

36 records · Page 2Linked to original sources
PubMed2004

No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study.

Phototherapy of skin diseases such as psoriasis is an effective and safe treatment modality. However, increasing the risk of skin cancer by phototherapy is a serious concern. An increased skin cancer risk occurs after prolonged photochemotherapy (PUVA). In contrast, the role of broadband UVB or narrowband UVB therapy in skin carcinogenesis of humans with psoriasis is less clear. Therefore, we investigated the incidence of skin tumours in a total of 195 psoriasis patients, receiving broadband (n=69) or narrowband (n=126) UVB from 1994 to 2000 with follow-up until 2003. Data were raised from the regional interdisciplinary cancer centre of the University of Tuebingen, Germany and compared with the tumour incidences given for the German population. In this study, with 80% statistical power to detect a 6-7-fold increase in skin cancer with broadband UVB and 83% power to detect a 5-6-fold increase with narrow band UVB at p=0.05, only one patient developed skin cancer - an in situ melanoma. The tumour occurred within the same year that phototherapy was initiated. Thus, the present study does not provide evidence for an increased skin cancer risk for patients treated with either broadband or narrowband UVB phototherapy

Carcinoma in Situ↗
PubMed2003

The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors.

Nonmelanoma skin cancer is the most commonly diagnosed malignant disease in Caucasians. Known risk factors include fair skin, sun exposure, male gender, advancing age, and the presence of solar keratosis. No viral risk factors have been established thus far. To examine the association between nonmelanoma skin cancer and infection with human papilloma virus (HPV) types, we performed a retrospective study in which skin biopsies were collected from 496 nonimmunosuppressed patients attending dermatologic clinics during a defined period and for whom a biopsy or resection of a tumor was indicated for medical reasons. A total of 390 patients with histologically confirmed diagnosis of warts (n = 209), solar keratosis or Bowen's disease (n = 91), squamous cell carcinoma (n = 72), or basal cell carcinoma (n = 18), as well as 106 control patients with normal skin was analyzed for infection with HPV and, if positive, HPV typed by sequencing. Logistic regression was performed to separately investigate association of certain HPV types with the occurrence of warts, precancerous lesions, and skin cancer compared with normal skin. For all three histological groups, both crude risk and risk adjusted for age, sex, and sun exposure were calculated. HPV DNA was detected in only 4.7% of controls, in 90.9% of benign warts, in 60.4% of precancerous lesions, in 59.7% of squamous cell carcinoma, and in 27.8% of basal cell carcinoma, which demonstrates that viral infection is specifically linked to skin disorders. The distribution of viral types found is distinctly different between warts and precancers or cancers, supporting an etiologic role of specific HPV types. This is supported by statistical analysis, where after adjusting for age, gender, and sun exposure, the odds ratio for nonmelanoma skin cancer in patients who were DNA positive for the high-risk mucosal HPV types, 16, 31, 35, and 51 was 59 (95% confidence interval, 5.4-645) with normal skin as controls. These findings suggest that persistent infections of the skin with high risk genital HPV types recently identified as significant risk factors for cervical cancer may also represent a risk factor for nonmelanoma skin cancer in a nonimmunosuppressed population.

Adolescent↗
PubMed2003

Functional characterization of the human 11 beta-hydroxysteroid dehydrogenase 1B (11 beta-HSD 1B) variant.

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD 1) catalyzes the interconversion of inactive into active glucocorticoids and has been shown to play a key role in metabolic disorders such as obesity and diabetes. 11 beta-HSD 1 belongs to the short chain dehydrogenases/reductases (SDR) and shares all common structural motifs typically for this protein superfamily. Unlike common SDRs, 11 beta-HSD 1 is N-terminally extended by a hydrophobic domain that anchors this enzyme in the endoplasmic reticulum (ER) membrane. Interestingly, the occurrence of 11 beta-HSD 1 transcripts lacking the N-terminal hydrophobic domain has repeatedly been reported in a variety of tissues, and the corresponding protein has been named 11 beta-HSD 1B. So far, no activity of 11 beta-HSD 1B has been observed, such that a physiological role could not be ascribed. In the present investigation, we showed for the first time that the truncated human 11 beta-HSD 1B form, expressed in the yeast Pichia pastoris, may indeed be active. However, this activity was prevented by the fact that 11 beta-HSD 1B is still kept attached to the ER membrane. Via computer assisted simulation and modeling, we identified a putative domain within the 11 beta-HSD 1 structure that could be responsible for this additional membrane attachment. By performing site-directed mutagenesis, heterologous expression, immunoblot analysis, and activity assays, we verified that this hydrophobic domain could indeed interact with the ER membrane and that some of the introduced mutations (V149R, V149E) led to a release of 11 beta-HSD 1B from membrane attachment without affecting its enzymatic activity. However, the activity of 11 beta-HSD 1B proved to be very unstable and was lost within hours after solubilization and release from the ER membrane. Importantly, 11 beta-HSD 1 constructs lacking the first 15 N-terminal amino acids and bearing additional amino acid substitutions (t15-V149R, t15-V149E) were then found to be soluble and to be stable in terms of enzyme activity. Combined, despite its occurrence in mammalian tissues, 11 beta-HSD 1B has obviously no physiological role since it is either inactive while being attached to the ER or it is rapidly losing activity once being released from intracellular membranes. Our findings with the t15-V149R and t15-V149E constructs are promising to further understand the complex mechanical and structural properties of 11 beta-HSD 1.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

The critical role of the N-terminus of 11beta-hydroxysteroid dehydrogenase type 1, as being encoded by exon 1, for enzyme stabilization and activity.

11beta-Hydroxysteroid dehydrogenase type 1 catalyzes the conversion of cortisone to hormonally active cortisol and has been implicated in the pathogenesis of a number of disorders, including insulin resistance and obesity. Because 11beta-HSD 1 is a membrane protein with a very hydrophobic character, it is difficult to purify it in an active state. Not much is known about the topological and structural determinants of 11beta-HSD 1, although the elucidation of the structure of 11beta-HSD 1 would be a great advantage in identifying specific 11beta-HSD 1 inhibitors. Bacterial expression of full-length or truncated 11beta-HSD 1 forms only led to insoluble proteins or to low amounts of enzyme, not sufficient for crystallization. Recently, we reported that the solubility of 11beta-HSD 1 could be increased by substitution of hydrophobic amino acid residues with arginine without affecting activity. Unfortunately, these truncated and soluble forms of 11beta-HSD 1 exhibited an unstable activity that declined very rapidly. So far, the proteins obtained were not suitable for crystallization. To obtain 11beta-HSD 1 in an active and soluble state, in the present investigation we focused on the amino acid sequence encoded by the first exon. Using bacterial and yeast expression systems, we found that this N-terminal peptide could be divided into two parts that have functions other than to anchor 11beta-HSD 1 into the ER membrane. The first hydrophobic part, consisting of amino acid residues 1-15, represents the membrane spanning domain and anchors 11beta-HSD 1 in the ER membrane. The second hydrophilic part of the peptide, consisting of amino acid residues 16-30, plays a crucial role in stabilizing the catalytic domain of 11beta-HSD 1 and in addition, acts as a spacer to keep the catalytic domain of 11beta-HSD 1 into the lumen of the ER. Evidently, we found that the hydrophilic amino acids 24-30 determine 11beta-HSD 1 enzyme activity. Combined, all information obtained should help to design an optimal 11beta-HSD 1 enzyme in the near future with all desired attributes: soluble, active and easy to obtain and purify in sufficient amounts. This soluble and active 11beta-HSD 1 form should be the basis for our ongoing project, which is the determination of the three dimensional structure of 11beta-HSD 1.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Prospective evaluation of a follow-up schedule in cutaneous melanoma patients: recommendations for an effective follow-up strategy.

PURPOSE: To prospectively examine and evaluate the results of follow-up procedures in a large cohort of cutaneous melanoma patients. PATIENTS AND METHODS: This was a prospective study in 2,008 consecutive patients with stage I to IV cutaneous melanoma from 1996 to 1998 on the yield of stage-appropriate follow-up examinations according to the German guidelines. Documentation of patient and follow-up data comprised patient demography, primary tumor specifics, and any clinical and technical examinations performed. The detection of metastasis was classified as early or late, and the means of their detection and the resulting overall survival probabilities were examined. RESULTS: A total of 3,800 clinical examinations and 12,398 imaging techniques were documented. Sixty-two second primary melanomas in 46 patients and 233 disease recurrences in 112 patients were detected during this time. In stage I to III disease, physical examination was responsible for the discovery of 50% of all recurrences. In the primary tumor stages, 21% of all recurrences were discovered by lymph node sonography, with the majority being classified as early detection. Forty-eight percent of the recurrences were classified as early detection, and these patients had a significant benefit of overall survival probability. CONCLUSION: The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.

Cohort Studies↗
PubMed2003

Enzymology and molecular biology of glucocorticoid metabolism in humans.

Glucocorticoids (GCs) are a vital class of steroid hormones that are secreted by the adrenal cortex and that are regulated by ACTH largely under the control of the hypothalamic-pituitary-adrenal axis. GCs mediate profound and diverse physiological effects in vertebrates, ranging from development, metabolism, neurobiology, anti-inflammation and programmed cell death to many other fuctions. Multiple factors "downstream" of GC secretion, such as glucocorticoid receptor (GR) number and the abundance of plasma binding proteins have originally been considered as modulators of GC action. However, in the last decade the role of tissue-specific GC activating and inactivating enzymes have been identified as additional determinants in GC signalling pathways. On the cellular level, they function as important pre-receptor regulators by acting as "molecular switches" for receptor-active and receptor-inactive GC hormones. According to their biologic activity to catalyze the interconversion of C11-hydroxyl and C11-oxo GCs these enzymes have been named 11beta-hydroxysteroid dehydrogenase (11beta-HSD; EC 1.1.1.146). Two isoforms of 11beta-HSD have been cloned and characterized so far. 11beta-HSD type 1 is found in a wide range of tissues, acts predominantly as a reductase in intact cells and tissues by regenerating active cortisol from cortisone, and has been described to regulate GC access to the GR. 11beta-HSD type 2 is found mainly in mineralocorticoid target tissues such as kidney and colon, acts only as a dehydrogenase by producing inactive cortisone, and has been found to protect the mineralocorticoid receptor from high levels of receptor-active cortisol. Recently, 11beta-HSD 1 has become highly topical due to the finding that 11beta-HSD 1 plays a pivotal role in the pathogenesis of central obesity and the appearance of the metabolic syndrome. This review provides an overview on the components involved in GC signalling of 11beta-HSD type 1 as an important pre-receptor control enzyme that modulates activation of the GR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

[Psychosocial burden and subjective experience of melanoma patients in the ambulant follow-up].

INTRODUCTION: The ambulant follow-up is established for early detection of metastases thus improving the survival probability of tumor patients. In spite of the safety aimed at, follow-up also puts a burden on tumor patients and has effects on their quality of life. AIM: To investigate within the scope of follow-up, to collect data on the psychosocial burden on melanoma patients in relation to the predictors (medical factors, psychological variables, sociodemographic data) in order to define a "burden-risk patient". METHOD: From June to December 1997, 615 ambulant melanoma patients were questioned with the aid of the Hornheide questionnaire and the German version of the Hospital Anxiety and Depression Scale (HADS-D). RESULTS: The leading predictors for a psychosocial burden were found to be fear and depression, as well as tumor thickness, metastases, year of operation, sex, age, and marital status/household. With the aid of these results, a burden-risk patient could be defined: female sex, age between 40 and 59 years, divorced or widowed, separately living, with a tumor thickness of more than 4 mm, first diagnosis less than 3 years ago and prevailing metastases. This risk patient had also a high probability of having significant fear and depression values. CONCLUSION: The use of the Hornheide questionnaire for identifying the psychosocial burden is suitable to collect the individual burdens of the patients in particular and within a short period. In the same way, the needs of the patients can be met in particular, and thus his/her quality of life can be increased.

Adult↗
PubMed2003

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Algorithms↗
PubMed2003

Modified ABC-point list of dermoscopy: A simplified and highly accurate dermoscopic algorithm for the diagnosis of cutaneous melanocytic lesions.

BACKGROUND: The use of dermoscopy (epiluminescence microscopy, surface microscopy, dermatoscopy) improves clinical diagnostic sensitivity by 10% to 27%, particularly achieved by different algorithms or scores. OBJECTIVE: We sought to develop a simplified and highly accurate dermoscopic-point list for cutaneous melanocytic lesions. METHOD: We studied consecutive patients with suspicious melanocytic lesions, which were excised and histopathologically examined at our institution. On the basis of the ABCD rule of Stolz, Menzies score, and the modified ABCD rule of Kittler, a simplified ABC-point list was developed. Simple points were given for the following: asymmetry of outer shape (A) or differential structures inside the lesion in at least 1 axis ((A)); the abrupt cutoff of network at the border in at least one quarter of circumference (B); 3 or more colors (C); 3 or more differential structures (D); or noticed change (evolution) in the last 3 months (E). Using 20-fold magnification of computer dermoscopy, the sensitivity, specificity, and diagnostic accuracy were examined in 269 cutaneous melanocytic lesions. Of these, 84 (31.2%) were cutaneous melanomas. Also, the sensitivity, specificity, and diagnostic accuracy were investigated with a 7-point checklist and the 7 features for melanoma. RESULTS: With the ABC-point list for the diagnosis of cutaneous melanoma, sensitivity was 90.5%, specificity was 87%, and diagnostic accuracy was 88.1%, confirmed by cross-validation. The ABCD rule resulted in 90.5%, 72.4%, and 78.1%; Menzies score in 95.2%, 77.8%, and 83.3%; 7-point checklist in 90.5%, 87%, and 88.1%; and 7 features for melanoma in 94%, 74.6%, and 80.7%, respectively, CONCLUSIONS: The ABC-point list is simpler than the already established algorithms. Despite its simplicity, a high sensitivity, specificity, and diagnostic accuracy was achieved. This simplified approach in dermoscopic diagnostics may contribute to further spread and enable to learn and use this method more easily.

Algorithms↗
PubMed2002

[Skin cancer].

The current status, clinic, causes and prevention strategies of malignant tumours of the skin are described. Dermatologists, physicians and health professionals have made tremendous efforts to improve the public education and early detection of these tumours especially during the last decade. Further campaigns and continual medical education are demanded to continue this improvement for patients and public health system.

Basal Cell Carcinoma↗