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Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

At least 55 records · Page 3Linked to original sources
PubMed2001

Detection of melanoma cells in sentinel lymph nodes, bone marrow and peripheral blood by a reverse transcription-polymerase chain reaction assay in patients with primary cutaneous melanoma: association with Breslow's tumour thickness.

BACKGROUND: Tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) has been shown to be highly sensitive in detecting tumour cells in melanoma patients. OBJECTIVE: To assess whether the detection of minimal residual disease by RT-PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs), bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma. METHODS: Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients with primary cutaneous melanoma (tumour thickness > or = 0.75 mm) were examined by nested RT-PCR for tyrosinase and Melan-A. SLNs and BM samples were also analysed by histopathology. RT-PCR findings were related to tumour thickness of the primary melanoma. RESULTS: Overall, melanoma cells were detected by RT-PCR in 13 of 26 patients (50%). Seven patients had positive RT-PCR results in their SLNs (27%), including all patients (n = 4) with histologically positive SLNs, two patients had positive findings in their BM exclusively detected by RT-PCR (8%) and six patients in PB (23%). The presence of tumour cells detected by RT-PCR in SLNs was not related to the presence of melanoma cells in BM and/or PB. The incidence of RT-PCR-positive SLNs was significantly associated with greater tumour thickness (P = 0.004). Both patients with positive RT-PCR findings in their BM had a large tumour thickness (> or = 2 mm). No association between positive RT-PCR findings in PB and greater tumour thickness was observed. CONCLUSIONS: RT-PCR-positive SLNs were strongly associated with greater tumour thickness, underlining the prognostic significance of SLN positivity. Similar to certain epithelial malignancies, molecular investigation of the BM might provide complementary prognostic information in the early stages of melanoma. In contrast, no association between positive RT-PCR results in PB and increasing tumour thickness was found, implying that RT-PCR findings in PB are of doubtful clinical relevance in primary melanoma.

Adult↗
PubMed2001

Response of psoriasis to interleukin-10 is associated with suppression of cutaneous type 1 inflammation, downregulation of the epidermal interleukin-8/CXCR2 pathway and normalization of keratinocyte maturation.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Cell Differentiation↗
PubMed2001

HLA-A2 restricted, melanocyte-specific CD8(+) T lymphocytes detected in vitiligo patients are related to disease activity and are predominantly directed against MelanA/MART1.

Vitiligo is a skin and hair disorder characterized by circumscribed depigmented lesions due to lack of melanocytes in the respective areas. It has been suggested that vitiligo is caused by an autoimmune-mediated destruction of melanocytes. Recently, the presence of a high frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in the peripheral blood of patients with vitiligo was reported. Our study examines the frequency of melanocyte-specific cytotoxic T lymphocytes in vitiligo patients and its relationship to disease activity. Thirty-two patients with moderate to active vitiligo and 17 control subjects were included. Melanocyte specific reactive CD8(+) T cells were identified by enzyme-linked immunospot assay after stimulation with five peptides from gp100, four peptides from MelanA/MART1, and two peptides from tyrosinase. In selected patients, intracellular interferon-gamma staining for the detection of specific reactive CD8(+) T cells was additionally performed. In seven of 10 patients (70%) with actively progressive disease CD8(+) T cells directed against melanocyte epitopes were detected, whereas only in four of 22 patients (18%) with moderate disease activity such specific reactivity was found. MelanA/MART1 peptides were immunodominant in nine patients reacting against EAAGIGILTV and three patients reacting against ILTVILGVL. Intracellular interferon-gamma staining confirmed the findings obtained by the enzyme-linked immunospot technique. The present study supports the hypothesis that vitiligo is a cytotoxic T lymphocyte-mediated autoimmune disease. The presence of melanocyte-specific reactive CD8(+) T cells seems to be closely related to disease activity.

Adult↗
PubMed2001

Does intensive histopathological workup by serial sectioning increase the detection of lymph node micrometastasis in patients with primary cutaneous melanoma?

Various histopathological techniques have been developed in order to improve the detection of micrometastasis in the regional lymph nodes of patients with malignant melanoma. Our standard histopathological examination of lymph nodes included haematoxylin and eosin (H & E) staining and immunohistochemistry (IH) using antibodies to HMB-45 and S-100 proteins of three paraffin sections at one level. In addition, lymph nodes were examined by molecular biological methods using tyrosinase reverse transcription-polymerase chain reaction (RT-PCR). In this study, we investigated the use of step sections and IH in lymph nodes regarded as negative by standard histopathology but positive by tyrosinase RT-PCR, suggesting the presence of tumour cells. In a series of 76 consecutive patients with stage I and II cutaneous melanoma, a total of 156 regional lymph nodes were examined by H & E staining, IH and tyrosinase RT-PCR. All lymph nodes were bisected along their long axis for separate evaluation. In 21 patients, at least one lymph node in the regional nodal basin reported as tumour-negative by standard histopathology was demonstrated to express tyrosinase (total number of nodes = 33). These 33 lymph nodes were re-examined by H & E and IH at 10 additional levels of the paraffin block. Only one lymph node from one patient had occult melanoma cells in deeper levels detected exclusively by IH. Six out of 20 patients with positive findings exclusively on tyrosinase RT-PCR developed tumour recurrences during a median follow-up of 34 months. We therefore conclude that additional step sectioning with IH does not significantly increase the detection of tumour-positive lymph nodes. Patients with melanoma cells detected exclusively by RT-PCR, however, were shown to be at increased risk for tumour recurrence.

Adult↗
PubMed2001

Hyperkeratosis lenticularis perstans (Flegel's disease)--lack of response to treatment with tacalcitol and calcipotriol.

Hyperkeratosis lenticularis perstans (HLP) or Flegel's disease is a rare dermatosis characterized by asymptomatic hyperkeratotic papules predominantly located on the lower extremities. Lesional and non-lesional epidermis samples were studied by light- and electron-microscopic examination. The main ultrastructural finding was the presence of structurally altered Odland bodies/membrane-coating granules. Different therapeutic options for HLP have been reported, but none of the treatments was shown to be consistently effective. Here, we report on a patient with Flegel's disease who did respond to topical 5-fluorouracil, whereas topical vitamin D(3) synthetics were ineffective.

Calcitriol↗
PubMed2001

The dermatoscopic pattern of clear-cell acanthoma resembles psoriasis vulgaris.

BACKGROUND: Dermatoscopy (dermoscopy, epiluminescence microscopy) is used for the early detection of malignant tumors and avoidance of unnecessary excisions of benign skin tumors. OBJECTIVE: Description of the dermatoscopic pattern of clear-cell acanthoma. METHODS: Video dermatoscopy at 20-fold magnification of a clear-cell acanthoma and psoriasis vulgaris. RESULTS: Homogeneous, symmetrically or bunch-like arranged, pinpoint-like capillaries were seen in the clear-cell acanthoma and in psoriasis vulgaris. CONCLUSION: The dermatoscopic psoriasis-like pattern of clear-cell acanthoma is a diagnostic clue which may help the clinician to identify this benign epidermal tumor and to differentiate it from other benign and malignant tumors of the skin.

Capillaries↗
PubMed2000

Time trends of cutaneous melanoma in Queensland, Australia and Central Europe.

BACKGROUND: The objective of this study was to describe recent developments in cutaneous melanoma from the German speaking countries in Europe (Germany, Austria, and Switzerland) and from Queensland, Australia. METHODS: All incident invasive cutaneous melanoma cases recorded between 1986 and 1996 by the Queensland Melanoma Register and by the Central Malignant Melanoma Registry of the German Dermatological Society were included in the analysis. Weighted linear trend analyses were performed to assess significant changes over the years using yearly sample sizes as weights. RESULTS: In Central Europe, the median tumor thickness decreased from 1.2 mm in 1986 to 0.8 mm in 1996 (P < 0.001), whereas it varied insignificantly between 0.5 mm and 0.6 mm in Queensland. The percentage of patients with Clark Level II invasion increased significantly in Queensland (P < 0.001; 1996, 61.1%) and in Central Europe (P = 0.041; 1996, 24.5%). The percentage of superficial spreading melanomas rose in Central Europe (P = 0.043; 1996, 64.4%), whereas it decreased slightly in Queensland (P = 0.032; 1996, 75%). In Queensland and in Central Europe, younger people and women presented more frequently with thinner melanomas (</= 0.75 mm). CONCLUSIONS: In both Central Europe and Queensland, trends toward thinner and less invasive melanomas were observed between 1986 and 1996, although the median tumor thickness decreased significantly only for Central European data. Men and elderly individuals should be the focus of health-promotion activities, because they tended to present on average with thicker and prognostically poorer melanomas.

Adult↗
PubMed2000

Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma: results of a prospective study of 1288 patients.

BACKGROUND: In regional lymph node metastasis of cutaneous melanoma, the number and volume of involved lymph nodes are the most important prognostic factors. Several studies have revealed that palpation of the lymphatic drainage area(s) and regional lymph nodes has a high rate of false-negative results during follow-up. The aim of the current study was to assess the sensitivity and specificity of ultrasound versus clinical diagnosis in the detection of subcutaneous and regional metastases. METHODS: During a period of 42 months, a total of 6328 lymphatic drainage areas were examined clinically and by ultrasound (7.5-10 MHz) in 1288 melanoma patients at 4435 follow-up consultations. When an ultrasound finding was suggestive of metastasis, surgery and histopathologic evaluation were performed. The results of clinical examination, ultrasound examination, and histopathologic findings were compared. RESULTS: In 504 ultrasound examinations performed on 235 patients, metastatic disease was diagnosed in 263 examinations following surgery (179 patients). Due to advanced disease or rejection, an additional 56 patients did not undergo surgery. In 239 of the 263 positive findings (90.9%), metastases from melanoma were histopathologically confirmed. In 8 cases (3%) a second malignancy and in 16 cases (6. 1%) benign lymphadenopathy was histopathologically diagnosed. Palpation of subcutaneous lymph nodes and lymph nodes gave false-negative results in 68 of the 238 cases of histopathologically proven metastases (28.6%). Clinical examination was least sensitive in the supraclavicular, axillary, and infraclavicular regions. The sensitivity and specificity for ultrasound examination were 89.2% and 99.7%, respectively, and 71.4% and 99.7% for clinical examination, respectively. CONCLUSIONS: For early diagnosis of in-transit and regional lymph node metastases in cutaneous melanoma, ultrasound scanning is distinctly superior to clinical examination. Controlled follow-up studies are proposed to examine the possible beneficial effects on survival time resulting from the ultrasound examinations of the lymphatic drainage area(s) and regional lymph nodes.

Adult↗
PubMed2000

Agreement between self-assessment of melanocytic nevi by patients and dermatologic examination.

The number of melanocytic nevi is the strongest risk factor for cutaneous melanoma. As pigmented skin lesions are visible to everybody, the question has been raised about whether people can identify themselves as being at risk for melanoma through self-counting of moles. In 1991, a total of 513 central European melanoma patients and 498 controls were asked to count the total number of nevi and the number of atypical nevi on the whole body. Whole-body examination by dermatologists followed. Agreement was assessed on categorized nevus counts by means of ordinal kappa values and log-linear modeling. Study subjects significantly underestimated the total number of melanocytic nevi (p < 0.0001). Chance-corrected overall agreement was rather poor (kappa = 0.14), and the ability to detect many existing nevi was low. Agreement was higher for atypical melanocytic nevi counts (kappa = 0.37), and the sensitivity to detect more than one atypical nevus was 0.48. Self-assessment of the number of melanocytic nevi was difficult to perform accurately, and people severely underestimated the actual number. Despite these results, people should be encouraged to perform regular skin self-examination for early detection of melanoma.

Adolescent↗
PubMed2000

Predictors of the use of sunscreen in dermatological patients in Central Europe.

BACKGROUND: There is mounting evidence that sun exposure is a cause of skin cancer. Therefore, the focus of skin cancer prevention is on sun protection. The present study investigated the use of sunscreens in a sample from the adult Central European population. METHODS: As part of a case-control study of cutaneous melanoma, a total of 498 controls with classical dermatological disorders were selected from hospitals in Central Europe. All people underwent whole-body skin examinations and were interviewed using a standardized questionnaire. RESULTS: Overall, 40.8% of the people never used sunscreen and of the 281 persons who used sunscreen, 41.5% applied it only once per sun bath. Persons who did not use sunscreen tended to be older (P<0.0001) and of male gender (P = 0.0004). Young people, women, and people who expressed a positive attitude to the sun spent more time in the sun and were more likely to apply sunscreens. People who worked almost always outdoors had a six times increased odds ratio of not using sunscreens (P<0.0001) compared to people who worked always indoors. CONCLUSIONS: Men, older people, and outdoor workers should be targeted in health education campaigns. On the other hand, people who apply sunscreen as a means of sun protection should be advised about adequate usage.

Adult↗
PubMed2000

[Shave excision of melanocytic nevi of the skin: indications, technique, results].

BACKGROUND AND OBJECTIVE: Shave excision of nevi is a technique still under debate. Speed, simplicity, and the fact that it provides excised material for histologic examination are contrasted with the lack of excision margins and a higher rate of nevus recurrences. In this study, the pros and cons of shave excision were evaluated. PATIENTS AND METHODS: Conventional excisions (268 nevi with intracutaneous butterfly sutures) and shave excisions (403 nevi) were compared with the patients' subjective assessments and objective parameters as recurrence, color, depth, surface smoothness of the scars, and the healing process. The nevi, found on the entire integument, ranged in diameter from 2 to 15 mm, with an average of 5 mm. A second excision was performed only in cases in which an early malignant melanoma could not be excluded. RESULTS: Shave excisions were evaluated subjectively as being better. Shave excisions resulted in fewer complications (7.9% versus 15%), but recurrences were more frequent (18.1% versus 6.0%). There was no close relationship between histopathologic finding of complete excision and recurrences. CONCLUSIONS: Small nevi without clinical suspicion of malignant melanoma can be removed with the shave excision technique with good results. Patients should be informed about the higher rate of recurrences. The appliance of the shave technique requires exact knowledge and experience, enabling good histopathologic examinations.

Biopsy↗
PubMed2000

Bacillus subtilis spore film dosimeters in personal dosimetry for occupational solar ultraviolet exposure.

OBJECTIVE: Ultraviolet (UV) radiation is noted to be one of the most important risk factors for nonmelanoma and melanoma skin cancers. The recent development of a spore film test chamber containing spores of Bacillus subtilis resulted in a new method of UV measurement with a spectral sensitivity profile similar to erythema-weighted data calculated from spectroradiometric measurements. METHODS: The practical application of dosimeters was tested on 11 persons for 43 days, under different conditions of UV exposure in five different geographical regions. Four professional lifeguards at a public swimming pool carried dosimeters attached to their shoulders or to their caps, for 11 days. Three mountain guides attached dosimeters laterally to their heads on 27 different occasions of mountaineering activity in different mountain regions. Four ski instructors carried lateral head dosimeters during eight days of skiing in the Alps. RESULTS: The life guards received daily UV exposures ranging from 3.6 to 9.5 minimal erythema doses (MED) (mean 5.9, SD +/- 1.9). The mountain guides had personal daily UV exposures of from 4.4 to 17.1 MED (11.9 +/- 3.9) and ski instructors from 2.8 to 8.8 MED (6.1 +/- 1.8). CONCLUSIONS: Bacillus subtilis spore film dosimeters can be applied effectively for personal solar UV measurements of occupationally exposed persons. such as lifeguards. mountain guides and ski instructors. UV levels in these occupations exceed international limits of exposure.

Bacillus subtilis↗
PubMed2000

Human melanoma progression in skin reconstructs : biological significance of bFGF.

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.

Basement Membrane↗