-
[show abstract]
[hide abstract]
ABSTRACT: The efficacy of treatment with fotemustine and interferon (IFN) alpha was evaluated in metastatic melanoma. A group of 50 patients with metastatic malignant melanoma were treated with a combination of IFNalpha2b and the nitrosourea fotemustine. The patients received 10 MU IFN three times weekly for 3 weeks and fotemustine at a dose of 100 mg/m2 on days 8, 15 and 22. After a 5-week rest period, patients with stabilized or responding disease received a maintenance therapy consisting of 10 MU IFN three times a week for 1 week followed by administration of fotemustine (100 mg/m2) on day 8. This cycle was repeated every 4 weeks until progression occurred. If there was complete remission (CR), treatment was stopped after an additional three cycles. Toxicity and clinical response were scored according to WHO criteria. Objective response was seen in 14 patients (28%; 95% confidence interval 15.6%-40.4%) with four CR and ten partial responses (PR). The median duration of CR was 73 weeks, that of PR 26 weeks. Toxicity was acceptable, enabling treatment on an outpatient basis. The combination of fotemustine with IFNalpha is effective and well tolerated, but there is no evident advantage over fotemustine monotherapy in the treatment of metastatic melanoma.
Journal of Cancer Research and Clinical Oncology 01/1998; 124(1):55-9. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Flow cytometric analysis of T-cell surface markers in peripheral blood has revealed abnormal patterns in patients with cutaneous T-cell lymphomas (CTCL). Here we investigated CD7, CD25, CD45RO and CD45RA expression on CD4+ T-lymphocytes in patients with CTCL stage I/II and III/IV and in patients with severe inflammatory skin diseases (ISD), as well as in healthy controls. Only late stage CTCL (III/IV) showed a lymphocytosis with a distinct surface marker pattern: CD3+, CD4+, CD8-, CD7-, CD45RO+, CD45RA-. Early stage CTCL (I/II) showed normal lymphocyte counts, a normal T-helper cell expression of CD7, CD45RO and CD45RA, and a slightly increased percentage of CD4+ CD25+ lymphocytes, which was also found in ISD. It is concluded that flow cytometric analysis of the above T-cell surface markers may be useful in the diagnosis of patients with late stage CTCL. However it does not allow us to distinguish patients with early stage CTCL from patients with ISD or controls.
Acta Dermato Venereologica 02/1996; 76(1):34-6. · 3.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6, IL-8 and IFN-gamma synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultured. Lymphocytes from patients with AE showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernatants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes, significantly enhanced amounts of IL-6 and IL-8, compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in IFN gamma production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-gamma in normal donors and in patients with AE. Interestingly, HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-gamma. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernatants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6, IL-8 and IFN-gamma; (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyte inhibitory soluble factors and IL-6, IL-8 as well as IFN-gamma; and (iii) secretion and/or activity of keratinocyte-derived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.
British Journal of Dermatology 12/1995; 133(5):750-6. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Summary Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6. IL-8 and IFN-γ synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultttred. Lymphocytes from patients with AH showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernalants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes. significantly enhanced amounts of IL-6 and IL-8. compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in TFN-γ production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-γ in normal donors and in patients with AE. Interestingly. HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-γ. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernalants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6. IL-8 and IEN-γ (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyle inhibitory soluble factors and IL-6, IL-8 as well as IFN-γ and (iii) secretion and/or activity of keratinocytederived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.
British Journal of Dermatology 10/1995; 133(5):750 - 756. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Twenty-two patients with severe atopic eczema were included in a therapy study with UV-A1 (wavelengths > 340 nm) treatment. The patients were divided into two dose groups, each consisting of 11 patients. One group received 10 J/cm2 and the other 50 J/cm2 five times a week for 3 consecutive weeks. No topical or systemical steroids or antihistamines were allowed. Using the SCORAD index as a measure of disease activity before onset of therapy and after 10 and 15 treatments, we observed a significant improvement in both dose groups after 15 treatments (10 J/cm2: p < 0.05, 50 J/cm2: p < 0.005). After 10 treatments only the improvement in the 50 J/cm2 group was significant (p < 0.005); the difference between the two dose groups was significant (p < 0.05). The clinical efficacy of treatment was reflected neither by a decrease of serum IgE nor by a decrease of elevated serum levels of soluble adhesion molecules sICAM-1 and sELAM-1 in the two dose groups. In contrast, a marked but not significant decrease of serum ECP could be observed in the 50 J/cm2 group only. We conclude from these and other published data that although 10 J/cm2 UV-A1 has a limited effect on patients with severe atopic eczema, higher doses are of higher efficiency in the treatment of this condition.
Acta Dermato Venereologica 02/1995; 75(1):43-5. · 3.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ICAM-1 is known to be strongly expressed on keratinocytes in lesional atopic eczema correlating with the degree of inflammation. ELAM-1 was found to be expressed on dermal vascular endothelium in lesional atopic eczematous skin.
The present study was performed to investigate whether elevated serum levels of soluble forms of these molecules are detectable in patients with severe atopic eczema and whether these parameters could be useful markers for disease activity.
Serum levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1) were measured by ELISA in 18 patients with severe atopic eczema before and after UVA1 therapy.
Before onset of treatment, serum sICAM-1 (565 +/- 99 ng/ml) and sELAM-1 (89.7 +/- 29.9 ng/ml) levels were significantly (p < 0.001) elevated compared to 22 healthy control persons (296 +/- 46 and 48.8 +/- 22.7 ng/ml). After achievement of significant clinical improvement after 3 weeks of UVA1 therapy, there was neither a decrease in serum sICAM-1 nor in sELAM-1 levels. The posttherapeutic serum sICAM-1 and sELAM-1 values remained elevated (p < 0.001) above the normal range.
Based on these data we suggest that (1) serum sICAM-1 and sELAM-1 are elevated in patients with severe atopic eczema, (2) sICAM-1 does not decrease together with reduction of ICAM-1-positive keratinocytes in atopic eczema following clinical improvement and might therefore be mainly of a different origin, i.e. leukocytes/endothelial cells, and that (3) sICAM-1 and sELAM-1 seem not to be suitable markers of actual disease activity in severe atopic eczema.
Dermatology 01/1995; 190(1):14-8. · 2.05 Impact Factor
-
Archives for Dermatological Research 02/1994; 286(7):414-6. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In human papillomavirus-associated acanthomas of the mamilla it was possible to detect DNA of HPV types 41, 6ma and a type related to type 16. The biology of HPV infection resembles that of anogenital lesions. Some of the HPV types found are rare or are thought possibly to have oncogenic potency. Possible evidence for link between HPV and carcinomas of the breast is discussed.
Der Hautarzt 11/1993; 44(10):644-6. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Herpes simplex virus (HSV) infections causing severe disease are reported frequently in patients suffering from human immunodeficiency virus (HIV) infection. This disease pattern may also be seen in an immunocompromised disease state with other causes, however, as in the case presented in this paper. An 84-year-old woman had hepatic cirrhosis resulting from chronic hepatitis C virus infection. The woman developed ulcerative lesions in and around her mouth and in the genito-anal region, and these persisted for some months. Diagnosis of HSV infection was not obtained until after extensive laboratory investigations. Aciclovir infusion therapy started immediately afterwards led to dramatic improvement of the skin and mucous membrane changes. Complete clearing of lesions was not obtained, however, because the patient died as a result of the immunosuppression.
Der Hautarzt 11/1993; 44(10):670-3. · 0.58 Impact Factor
-
Archives for Dermatological Research 02/1993; 285(4):233-5. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Biopsy-proven bowenoid actinic keratosis located in the pretibial region in each of two elderly women (61 and 81 years) were treated with intralesional injections with a new recombinant beta-interferon. The treatment took the form of intralesional injections three times a week over 3 consecutive weeks. The dose per single injection was 1.5 or 1.0 MU interferon, respectively. Clinical and histological examinations showed a complete response in both patients. Controls up to 18 months showed no relapse. There were no flu-like side-effects. Leukocyte counts decreased by 2700 and 500 cells per microliter during therapy.
Der Hautarzt 07/1992; 43(6):373-5. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Follicular mucinosis is a primary idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective standard therapy for the benign group is unknown. We describe a patient with primary benign disseminated progressive follicular mucinosis who was successfully treated with recombinant interferon alfa-2b and interferon-gamma. Interferons might act by down-regulation of activated inflammatory cells and/or by induction of enhanced elimination of extracellular mucin via increasing phagocytosis by macrophages.
Journal of the American Academy of Dermatology 06/1991; 24(5 Pt 2):848-50. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 20-year-old man complained of pulse-synchronous noise in the ear and recurrent bleedings in the nose and throat region. From birth he had had an extensive haemangioma, black-blue with dark-red parts. It had been diagnosed as a cavernous haemangioma, part of a Sturge-Weber syndrome. An angiogram was performed before intended dermatological treatment of the disfiguring venous angioma. It demonstrated the capillary venous angioma (slow-flow angioma) in the lateral triangle of the neck, extending up to the skull base. In addition there was an arteriovenous angioma (high flow angioma) in the region of the clivus, which was supplied bilaterally largely by the ascending pharyngeal artery. The arteriovenous angioma also had connections to the outflow area of the capillary venous angioma. These findings and absence of ocular changes excluded Sturge-Weber syndrome. Because of the risk of life-threatening bleedings, the arteriovenous malformation was superselectively embolized by multiple injections of nonresorbable polyvinyl-alcohol particles via a microcatheter. This brought about the collapse of the cutaneous angiomatous spaces. This case demonstrates that external appearance indicating a capillary venous angioma is not reliable. Before treatment of this malformation a neuroradiological diagnosis should be undertaken.
DMW - Deutsche Medizinische Wochenschrift 04/1991; 116(11):416-20. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sweet's syndrome (acute febrile neutrophilic dermatosis) occurred in a 29-year-old woman with acne. Although Sweet's syndrome initially seemed to be triggered by an acute acne flare, minocycline could later be identified as the causal agent. Because this could be confirmed in an oral provocation test, this seems to be the first case of a true connection between Sweet's syndrome and its induction by a drug, namely minocycline.
Dermatologica 02/1991; 182(1):43-6.
-
Archives of Dermatology 12/1990; 126(11):1515-6. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A case is described of a man with multiple papillomas on the nipple that resembled clinically and histologically condylomata acuminata. Human papillomavirus (HPV) type 41 DNA sequences were detected in the biopsy material. There was no evidence of any immunodeficiency.
British Journal of Dermatology 07/1990; 122(6):757-62. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Eighteen patients with advanced metastatic malignant melanoma (stage IVUICC 1987) were entered into a prospective trial with a combination of systemic fibroblast interferon-beta and recombinant interferon-gamma. Treatment was performed over a 6-week period with 3 x 5 x 10(6) U i.v. interferon-beta and 5 X 100 micrograms s.c. interferon-gamma every week. Under this therapy 16 patients showed a progressive disease, and 2 patients had a stable disease. The median time of survival was 7.5 months. Successive immunological examinations showed no significant immunomodulating effect after the 6 weeks of interferon treatment. We conclude that the combination of interferon-beta and -gamma is insufficient in the treatment of advanced metastatic malignant melanoma when administered by this dose, route and schedule.
Dermatologica 02/1990; 181(4):298-303.
-
[show abstract]
[hide abstract]
ABSTRACT: Cryosurgery is a well-known, established method for the local destruction of tumor tissue by freezing. The assumption that, in addition to a physical and blood vascular phase, an immunological phase exists, has been discussed by many authors and tested using animal models. These results can only be transferred to humans in a limited sense. During the last year, we initiated a randomized study "Cryosurgery versus Conventional Surgery", whereby the peripheral blood and the normal skin from the areas surrounding the resection were compared. We were able to demonstrate in the peripheral blood of 8 cryosurgery patients a postoperative increase in the total and helper T-cells, HLA-DR-positive cells, and the ratio helper/suppressor T-cells in comparison to preoperative values. In the 8 patients treated with conventional surgery, these parameters decreased slightly or remained the same. The differences were highly significant (p = 0.001) to significant (p = 0.01). The results from the first 16 are patients studied presented and discussed here.
Onkologie 01/1990; 12(6):291-6. · 0.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a patient suffering from benign lesions of epidermodysplasia verruciformis due to human papillomavirus type 5 little clinical improvement could be observed after 6 months of oral etretinate. The drug was given 75 mg/day for 1 month before dosage was reduced to 50 mg/day. Control biopsy after 3 months of treatment still revealed large quantities of virions and typical cytopathic effects in light and electron microscopic examination.
Dermatologica 02/1986; 173(2):75-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Sweet’s syndrome (acute febrile neutrophilic dermatosis) occurred in a 29-year-old woman with acne. Although Sweet’s syndrome initially seemed to be triggered by an acute acne flare, minocycline could later be identified as the causal agent. Because this could be confirmed in an oral provocation test, this seems to be the first case of a true connection between Sweet’s syndrome and its induction by a drug, namely minocycline.
Dermatology 08/1970; 182(1):43-46. · 2.05 Impact Factor
