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Biomedical subjects

W Tilgen

Publications and source records attributed to W Tilgen.

At least 19 recordsLinked to original sources

[Generalized hyperpigmentation and malignant acanthosis nigricans. A case of a patient with hereditary hemochromatosis and gastric cancer].

A 56-year-old previously healthy man developed hyperpigmentation of the entire skin over the previous 6 months without any other signs of further impairment. Additionally, we found accentuated skin lines of the neck and intertriginous sites as well as cutaneous papillomatosis. Histological examinations, laboratory tests and technical diagnostics revealed the existence of both hereditary hemochromatosis and adenocarcinoma of the stomach. Simultaneous manifestation of hyperpigmentation as a result of hemochromatosis as well as malignant acanthosis nigricans as a paraneoplastic symptom in gastric cancer is very rare.

Acanthosis Nigricans↗

[Established and current procedures in wound healing].

Most chronic wounds are caused by arterial or venous vascular disease. Wound care is an interdisciplinary task and economic challenge. Numerous new wound dressings and treatment methods have been introduced recently. Basic research has enhanced our understanding of stimulation and inhibition of wound healing. Well-constructed clinical studies have shown some traditional approaches to be effective and others, less so. Successful wound healing requires treatment of the underlying disease as well as correction of local factors that may delay healing. The choice of dressings must be based on continuous re-assessment of the wound. Modern approaches for the most common types of chronic wounds, as well as options such as vacuum treatment and tissue-engineered skin are presented along with information on latest rules for reimbursement for wound care in Germany.

Bandages↗

Incidence of antiretinal antibodies in melanoma: screening of 77 serum samples from 51 patients with American Joint Committee on Cancer stage I-IV.

BACKGROUND: Patients with melanoma-associated retinopathy (MAR) experience different visual symptoms caused by the production of antitumoral antibodies that cross-react with retinal epitopes. Immunofluorescence assays of serum from patients with MAR on sectioned monkey or human retina characteristically reveal antibody activity located within the inner nuclear layer, with a focus of activity upon the membranes of bipolar cells. OBJECTIVES: We inquired into the association with disease of this serological abnormality by evaluating sera from patients with melanoma with no MAR-like signs or symptoms. METHODS: Groups of patients were selected with different stages of melanoma (American Joint Committee on Cancer stages I-IV). Seventy-seven serum samples from 51 patients with melanoma were examined by indirect immunohistochemical assay on sections of human retina. RESULTS: Of the 77 serum samples, 53 were found to contain antibodies reactive with various components of retina. Eight were from 17 sera from patients in stage I or II, 14 were from 23 sera from patients in stage III, and 31 were from 37 sera from patients in stage IV. Statistical analysis revealed a correlation between antibody activity and the stage of disease, with a higher percentage of antibody activity in advanced stages (P = 0.002). CONCLUSIONS: The presence of antiretinal antibodies in patients with melanoma without ocular symptoms appears to be more common than previously suspected. Antibody activity similar to that ascribed to the MAR syndrome appears in some patients with melanoma who have no MAR-like retinopathy. Follow-up studies will determine if patients with antiretinal antibodies go on to develop MAR and if staining intensity and staining patterns change over the course of the disease.

Adult↗

[Complete remission of cutaneous satellite and in-transit metastases. After intralesional therapy with interleukin-2 in 2 patients with malignant melanoma].

Multiple cutaneous satellite and in-transit metastases of melanoma without involvement of lymph nodes or other organs are a challenge especially when they occur in elderly inoperable patients with multiple internal diseases. In this particular situation, intralesional application of interleukin-2 may represent an effective alternative to systemic chemo- or immunotherapy as it can be performed on an out-patient basis and has few side effects. We treated two elderly female patients with multiple cutaneous metastases of malignant melanoma with intra- and perilesional application of interleukin-2 (3 x 6-12 Mio IE) over 12 weeks and achieved a complete remission of these metastases. In follow-up biopsies, no viable tumor cells were found. Despite a slight burning at the injection side and a transient local inflammatory reaction, the therapy was well tolerated in both cases after premedication with paracetamol 500 mg orally and pretreatment of the injection site with a cream containing lidocaine and prilocaine. No systemic side effects were observed.

Aged↗

[Vacuum assisted wound closure after excision of a high risk melanoma heel wound - using the v.a.C. heel-dressing].

Vacuum-assisted wound closure is established in acute wound treatment and assists granulation tissue as well as promotion of graft survival in critical localisation. A new vacuum-assisted wound closure device is launched for the treatment of heel wounds (V.A.C. GranuFoam Heel Dressing). First experience with this heel contour shaped dressing is presented in a case of primary surgical care of a high risk melanoma. The initial defect after excision, measuring 8 x 6 x 3.5 cm, granulated by V.A.C. treatment in 5 weeks to skin surface niveau and was successfully covered with a full thickness skin graft. The V.A.C. Heel Dressing is easy to apply, reduces vacuum leakage und increases patients' comfort and treatment safety in comparison to "classic" vacuum dressings.

Debridement↗

[Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma].

PURPOSE: The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases. PATIENTS AND METHODS: Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m(-2) on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d(-1), days 1-5, 3 consecutive weeks). RESULTS: Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test). CONCLUSION: Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗

Melanoma-associated retinopathy: high frequency of subclinical findings in patients with melanoma.

BACKGROUND: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome with symptoms of night blindness, light sensations, visual loss, defect in visual fields, and reduced b-waves in the electroretinogram. Patients with MAR often suffer from a sudden onset of ocular symptoms that are believed to result from antibody production against melanoma-associated antigens that cross-react with corresponding epitopes on retinal depolarizing bipolar cells. OBJECTIVES: To correlate the frequency of subclinical symptoms suggestive of MAR in melanoma patients to different stages of disease, patient age, type and thickness of the primary tumour, form of therapy, S-100 level and tumour burden. METHODS: We analysed 28 patients with melanoma in stages I-IV (according to the American Joint Committee on Cancer tumour classification) for the presence of subclinical MAR symptoms using scotopic electroretinography, static and kinetic perimetry and nyctometry. RESULTS: Seven patients had clinical signs and symptoms consistent with MAR, 18 had some indications, while the remaining three had none. We found no correlation between clinical symptoms and stage of disease, tumour burden or S-100 level, but findings suggestive of MAR were observed more frequently in advanced stages of disease. CONCLUSIONS: Subclinical retinal involvement characteristic of MAR appears to be more common than previously suspected in patients with cutaneous malignant melanoma. Our findings in this small cohort seem to indicate that the percentage of patients with symptoms suggestive of MAR is higher in advanced stages of disease. Further clinical studies are required to evaluate if the presence of subclinical symptoms suggestive of MAR is correlated with a worse prognosis and a shortened progression-free and overall survival.

Adult↗

No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma.

Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF.

Adult↗

A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗

[Skin manifestations with internal diseases. Finding the origin].

Inspection of the skin in its entirety often turns up initial and orientating symptoms allowing the early detection of internal disorders. For example, the painful ulcerations of pyoderma gangrenosum can provide clues as to the presence of underlying inflammatory bowel or joint or hematologic disturbances. Extremely painful ulcerations with livedoid bleeding located on the lower limbs are indicative of calciphylaxis as a serious complication of terminal renal failure. Periorificial and migratory necrolytic erythema may signal a glucagon-producing carcinoma of the pancreatic islet cells. Pasty, whitish-yellow papules on the face associated with a tendency for developing petechiae may be a manifestation of amyloidosis in a plasmacytoma. Numerous diffuse angiomas covering the body of a younger patient should prompt the physician to consider the genetic enzyme defect of alpha-galactosidase (Fabry's disease). In the case of pacemaker- or defibrillator-associated erythema, unnecessary revision of the device can be avoided if such possibilities are considered. In consultation with the dermatologist, the exact classification of symptoms, an accurate diagnostic work-up, and differential-diagnostic considerations should be undertaken with the aim of enabling early initiation of causal or stabilizing treatments.

Biopsy↗

CD4+CD7- leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death.

In early stages of cutaneous T cell lymphoma (Sézary syndrome) both CD4+CD7- and CD4+CD7+ T cells clonally expand whereas in late stages of the disease CD7- cells are predominant in number, giving rise to the question whether CD7- T cells have a survival advantage in the skin. Galectin-1, a cell-bound lectin, was recently reported to trigger apoptosis in activated CD7+ T cells. Here, we demonstrate that in contrast to activated CD7(+) T cells, quiescent and activated CD69+ CD7- T cells from healthy donors and from Sézary patients are resistant to galectin-1-mediated cell death. CD7- T cells are apoptosis-resistant even during coculture with IFN-gamma-stimulated endothelial cells that constitutively express galectin-1 in high amounts. These data imply that resistance of CD7- T cells to galectin-1-induced apoptosis may contribute to the accumulation of CD7- Sézary T cells during progression of the disease.

Adjuvants, Immunologic↗

HLA-G in melanoma: A new strategy to escape from immunosurveillance?

The non-classical HLA class-I molecule HLA-G, primarily expressed on fetal cells of the human placenta, has been shown to play a crucial role in maintaining an immuno-privileged environment at the materno-fetal interface. Fetal trophoblast cells are protected from attack by CD8+ cytotoxic T lymphocytes due to their lacking expression of classical HLA class-I molecules, again rendering them susceptible to natural killer (NK) cell lysis. HLA-G has been shown to interact with killing inhibitory receptors, hereby rescuing the fetal placenta cells from NK cell attack. Likewise, classical HLA class-I molecules are known to be frequently downregulated or lost during the development of malignancies. This abnormality is often associated with a poor clinical course of disease, despite of the frequent detection of tumor-infiltrating NK cells. This controversy seemed to be resolved with the detection of HLA-G expression on cells of malignant melanoma and other solid tumors. Since interferon(IFN)s are known for their ability of upregulation or induction of HLA-G expression, the potential function of HLA-G as a new strategy of cancer cells to escape from immunosurveillance might be of particular importance in malignant melanoma. The frequent use of IFN-alpha in the immunotherapy of this malignancy might possibly worsen the already impaired antitumoral immune response state of melanoma patients. However, several studies recently failed to detect any HLA-G protein expression in cancer cell lines and tissues of different origin, particularly in malignant melanoma, yet rendering the expression and function of HLA-G in malignancies as a possibly overrated matter of controversial debate.

HLA Antigens↗