Search PubMed⌕ Search

Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

At least 181 records · Page 10Linked to original sources

[Erythroderma "en nappes claires" as a marker of metastatic kidney cancer. Lasting, successful treatment with rIFN-alpha-2a].

Two years after surgical removal of a renal cell carcinoma, a 70-year-old male patient developed generalized erythroderma and diffuse alopecia within a few days, which could not be further classified as a definite entity. The clinical picture showed well circumscribed roundish areas free of erythema, simulating normal skin (" nappes claires"). The skin disease was found to be resistant to systemic corticosteroids and oral retinoids, whereas in the laboratory work-up multiple lung metastases of the renal cell carcinoma were shown by computer tomography. The clinical picture and the course of the disease suggested a close relationship to the metastasizing visceral tumour, and the erythroderma was seen as a cutaneous marker of the internal neoplasia. A therapeutic trial with recombined interferon alpha-2a led to complete healing of the erythroderma within a few weeks and long-lasting stabilization of the metastasizing visceral tumour over 18 months.

Aged↗

[Borrelia infections of the skin--progress of knowledge since the discovery of Lyme disease].

The description of Lyme disease in 1976 and the detection of its causative agent, the spirochete Borrelia burgdorferi (B. burgdorferi), in 1982 led to an increase in our knowledge of the course of B. burgdorferi infection and its clinical manifestations. The classic tick-borne dermatoses erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LABC) and acrodermatitis chronica atrophicans (ACA) were proven by isolation of the spirochete from skin lesions to be caused by B. burgdorferi infection. In early disease (less than 1 year) ECM and LABC can develop locally at the site of infection (stage I), but both these skin manifestations can also occur together with multiple lesions after dissemination of the causative organism (stage II). ACA is typical for late infection (greater than 1 year, stage III). High titres of B. burgdorferi antibodies have been found in patients with localized sclerodermalike lesions (circumscribed scleroderma, lichen sclerosus et atrophicus, anetoderma), and frequent simultaneous occurrence of ACA suggests an association with late B. burgdorferi infection. Similarly, we found four cases of cutaneous B-cell lymphoma possibly arising from LABC in association with the same markers of late B. burgdorferi infection. Additionally, some cases of Schönlein-Henoch purpura and of Shulman syndrome may be associated with Lyme borreliosis. The disease is endemic in central Europe, and almost exclusively ticks of the Ixodes ricinus complex seem to transmit B. burgdorferi to humans, whereas the reservoir of infection seem to be rodents, especially mice. The main diagnostic tool is serological examination for B. burgdorferi antibodies, which will become detectable 3-6 weeks after infection. Enzyme-linked immunosorbent assay (ELISA) and the indirect immunofluorescence test (IFT) revealed similar sensitivity. In early disease, sensitivity for antibody detection could be improved by immunoblot technique and by flagellum-ELISA, which is specific for this early sensitizing B. burgdorferi antigen. For treatments, penicillin is no longer recommended as the drug of first choice, because low sensitivity of B. burgdorferi has been observed in vitro and in vivo. Tetracycline, doxycycline and amoxicillin p.o. are now preferred for the treatment of Lyme borreliosis, and in neurologic and cardiac abnormalities ceftriaxone i.v. is recommended. Treatment duration should be 14 days in early disease and 30 days in late disease.

Acrodermatitis↗

[Nevus associated malignant melanomas--diagnostic validation and prognosis].

The diagnosis and prognosis of naevus-associated malignant melanomas are examined in the present study. For this purpose, 581 cases of primary malignant melanoma seen in the University Department of Dermatology, Berlin Steglitz, were histologically investigated for naevus association. A naevocytic association was proven in 135 (23%) of the malignant melanoma biopsies. Naevocytic malignant melanomas were found at a significantly higher rate (P less than 0.01) in patients under 50 years of age. The 5-year survival rate for naevocytic melanomas was not significantly different from that for other malignant melanoma types: around 80% in both groups. An immunohistological evaluation of the diagnosis of naevus-associated melanoma was also performed on the basis of specimens from 89 melanocytic lesions. The use of HMB-45 for diagnosis of melanocytic tumours made it possible to differentiate resting dermal naevus cells from malignant melanoma infiltrates in paraffin sections in the present study, thus simplifying the diagnosis of naevus-associated malignant melanomas. However, dysplastic naevi, junctional naevi and juvenile melanomas are also stained by HMB-45, which means that malignant melanomas associated with junctional melanocytic naevi still cannot be reliably identified even today.

Adult↗

Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy.

Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10-10,000 U/ml rTNF-alpha applied for 72 h. The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments. The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE. Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha. In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment. On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant. The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment. Overall, rTNF-alpha enhanced the malignant immunophenotype of the cell lines tested. It increased the expression of the "late" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the "early" progression marker K.1.2. The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines. These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells. These effects may result in selection of rTNF-alpha-non-sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro.

Biomarkers, Tumor↗

Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype.

The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells.

Cell Differentiation↗

Staphylococcus aureus in atopic dermatitis and in nonatopic dermatitis.

Skin colonization with Staphylococcus aureus (S. aureus) was examined in 30 patients with atopic dermatitis (AD), in 25 patients with nonatopic eczema (NAE) and in 30 individuals as healthy controls (HC). Bacteria growth was examined in aerobic cultures and the population densities per dish were estimated; S. aureus colonization was found in the eczematous skin of 24 of 30 (80%) AD patients and in 13 of 25 (52%) NAE patients (NS, p greater than 0.1). In nonaffected skin S. aureus colonization was found in 19 of 30 (63%) of all AD patients compared with 6 of 25 (24%) in NAE patients and 1 of 30 (3%) in HC, respectively (p less than 0.05). In nonaffected skin, coagulase negative strains of staphylococcus were found in 25 of 30 (84%) controls and in 18 of 25 (72%) NAE patients compared with 12 of 30 (40%) patients with AD. It seems that colonization with S. aureus is not a characteristic feature for atopic dermatitis but is a frequent event in damaged skin; significantly elevated values were also observed in nonatopic eczema. The degree of colonization may depend on the severity and duration of the eczematous lesions.

Dermatitis, Atopic↗

[Interferon therapy in malignant melanoma].

Recent clinical trials on the systemic application of various forms of interferon in metastatic malignant melanoma showed a moderate response rate of about 11% on an average. Intralesional application of alpha- and beta-interferon, however, resulted in partial or complete regression of the metastases in approx. 50% of the tumors. At present, various combination studies are being carried out in order to enhance the anti-tumor effects of interferon and thus establish a potential therapeutic method in dermato-oncology. In this respect, the combination of alpha-interferon with classic cytostatic drugs (dacarbazine and vindesine) is especially encouraging.

Cell Division↗

[Anti-oncogram-oriented polychemotherapy in metastasizing squamous cell carcinoma of the skin: impressive partial remission].

Metastatic squamous cell carcinoma of the skin is associated with a poor prognosis even after surgical treatment or irradiation. Polychemotherapy can be used as an alternative regimen. We present a 65-year-old male patient with extensive metastatic squamous cell carcinoma of the skin after multiple surgical treatment and radiation. A combination of bleomycin, methotrexate and cisplatin, planned according to the anti-oncogram, resulted in rapid partial remission of the cutaneous metastases over several months.

Aged↗

[Initial therapy of acute unilateral epididymitis using ofloxacin. I. Clinical and microbiological findings].

In a prospective study, 70 men suffering from uncomplicated acute unilateral epididymitis were treated initially with 2 x 200 mg ofloxacin p.o. per day for 14 days. Patients were reexamined at the end of therapy and again after 6 and 12 weeks. Patients were retreated when the pathogens had not been eliminated. Aetiologically epididymitis was caused in one-third of cases each by C. trachomatis (n = 20) and common urinary tract pathogens (n = 20); in the remaining one-third we found N. gonorrhoeae (n = 1). U. urealyticum (n = 3), or no pathogens (n = 26). At the first check-up examination, in 64/70 patients no pathogens were found. Relevant bacteria were still detected in 6 patients: C. trachomatis in 5 and E. aerogenes in 1. After 12 weeks, infection still persisted in 3 patients (E. coli, P. aeruginosa, enterococci). In vitro the microorganisms were invariably sensitive to ofloxacin. Due to abscess formation, surgical intervention became necessary in 6 patients. In 3 of these cases the causative agent was C. trachomatis. Regardless of the aetiology, after 12 weeks, in 20% of our patients the epididymis was still infiltrated and 14% complained of persistent symptoms.

Acute Disease↗

[Initial therapy of acute unilateral epididymitis using ofloxacin. II. Andrological findings].

A total of 70 men suffering from uncomplicated acute unilateral epididymitis were enrolled in a prospective study. They were treated initially with 2 x 200 mg ofloxacin p.o. per day for 14 days, after which the spermatological examination was repeated for each. Ejaculate quality, i.e. density, motility, and morphology of spermatozoa, was determined on the last day of therapy, i.e. after 14 days, and again after 6 and 12 weeks. In most patients, initially decreased sperm counts increased significantly and global motility improved, while the numbers of abnormal spermatozoa decreased. Only in a few cases were azoospermia, kryptozoospermia, consistently reduced motility, and constant or even increasing numbers of deformed spermatozoa observed.

Acute Disease↗

[Chemotherapy of malignant melanoma--current status].

Curative treatment modalities for patients with malignant melanoma (MM) in advanced stages are limited. Temporary successes with chemotherapy have so far mainly been achieved after removal of all accessible tumor masses. Extensive experience with cytostatic measures has been gained over more than two decades both with therapeutic and with adjuvant schedules. Dacarbazine (DTIC), which is associated with a remission rate of approximately 20%, continues to be the most effective cytostatic drug in the treatment of MM. Systemic (poly) chemotherapeutic schedules with and without DTIC have improved the response rates in metastasizing MM in numerous phase II trials. However, these results have not been confirmed in randomized studies comparing these schedules with DTIC monochemotherapy. For the BOLD schedule (bleomycin, Oncovin, lomustine, dacarbazine), the BELD schedule (Eldisine instead of Oncovin), and the DVP combination (dacarbazine, vindesine, Platinex), initial response rates of 40-49% have been reported. However, lower response rates were recently described (DVP: 24%; BOLD: 22% and 4%). Therefore, there is still no definite evidence that polychemotherapy is superior to DTIC monotherapy in MM. In our opinion, expected response rates of 20-30% justify the use of chemotherapy in disseminated MM; in cases of further progression, therapy should be interrupted early - after 2-3 cycles. Systemic (poly) chemotherapy of metastasizing MM is indicated in patients whose general condition is good, mainly in those who have skin, soft tissue, or lung metastases. These metastases usually respond well to cytostatic treatment. In future, the combined use of cytostatics together with new antitumour molecules may reduce the general toxicity and improve the efficacy of systemic cytostatic therapy in MM. The benefits of adjuvant chemotherapy in the treatment of MM have still to be confirmed definitively. While adjuvant therapy with DTIC has proved to be ineffective in stage I, irrespective of the tumor thickness, some studies suggest that adjuvant therapy with DTIC, or combinations including DTIC, may improve the prognosis of patients in clinical stage II.

Antineoplastic Agents↗

[Pustular arthro-osteitis. Pustulosis palmaris et plantaris with arthritis of the sternoclavicular joint].

A 26-year-old female patient presented with pustulosis palmaris et plantaris simultaneously with arthritis of the sternoclavicular joint. This association is described as an entity and is called pustulotic arthroosteitis in the Japanese literature, as well as in publications from Scandinavia. To our knowledge, this is the first observation in the Federal Republic of Germany.

Adult↗

[Risk factors for the development of malignant melanoma in West Germany. Results of a multicenter-case control study].

In this multicenter case-control study (1,079 melanoma patients, 778 control persons), the significance of the well-known risk factors for the development of malignant melanoma (MM) was assessed for a German population. The multifactorial analysis of the data confirmed the total number of melanocytic nevi (MCN) as the most robust indicator for an increased melanoma risk. For persons with more than 50 MCN the relative risk was 4.8 times as high as for persons with fewer than 10 MCN. Hair color was found to be another valuable indicator. In persons with red hair the risk of MM was 4.7 that in individuals with black hair. Remarkably fair persons with skin type 1 (always sunburn, never tanning) had two times the risk of that in persons with skin type 4 (never sunburn, always tanning). The habit sun bathing for recreation showed no influence on the development of melanoma. A 2.7 x increased melanoma-risk was detected in persons with occupational sun exposure and out of doors work.

Case-Control Studies↗

[Ulcero-mutilating acro-osteopathy in hereditary neuropathies. Differential diagnosis and pathogenesis].

Two patients, aged 51 and 70 years, had indolent ulcerations at the sole of the foot with destructive osteolysis in the bones of the feet, lesions characteristic of mutilating ulcerative acro-osteopathy. Patient 1, who had pes cavus, developed ulcerations on the balls of the feet along the second metatarsal bones, and patient 2 with pes equinovarus developed ulcers in the area of the calcaneus. Sock-like hypesthesia/hypalgesia from the toes to the ankles was present in both patients, and electrophysiological tests confirmed the presence of axonal sensory-motor neuropathy. Diabetes mellitus and alcohol abuse was excluded in both patient. Clinical findings, history and neurological disturbances in both patients identified the disease as hereditary sensory neuropathy (type I).

Aged↗

Interferons in dermatology.

Interferons are a large family of proteins and glycoproteins, naturally occurring or artificially produced by recombinant biotechnology. Their antiviral, antiproliferative, antitumoral, and immunomodulatory activities are induced by alterations in cell metabolism after binding to specific membrane receptors. Interferons have been used for the treatment of viral papillomas (e.g., verruca vulgaris and condyloma acuminatum), human immunodeficiency virus (HIV)-associated Kaposi's sarcoma and cutaneous tumors (e.g., melanoma, cutaneous T cell lymphoma, and basal cell carcinoma), and inflammatory dermatoses (e.g., Behçet's syndrome and psoriatic arthropathy). Clinical trials have been performed worldwide with various regimens and have not always led to conclusive results. In our experience long-term therapy with high doses of subcutaneously injected, recombinant interferon-alpha-2a in patients with HIV-associated Kaposi's sarcoma induces a remission or stabilization of the disease. In malignant melanoma a low response rate is obtained in metastatic disease with the use of interferon as a single therapeutic agent. Combined with other antitumor agents, however, interferon seems to be a useful drug. Excellent control of Behçet's disease has been obtained, and the treatment of condylomata acuminata has been effective.

Humans↗

Markers and relative risk in a German population for developing malignant melanoma.

The relationship between cutaneous malignant melanoma (MM) and possible risk factors was assessed in a case-controlled study. Two hundred patients and 200 non-melanoma controls of German origin matched for age and sex were interviewed and examined for pigmented moles and pigmentation characteristics. In patients with MM significantly more melanocytic nevi greater than or equal to 2 mm (MCN) were found (mean, 53 MCN) compared to control cases (mean, 18 MCN). For persons with greater than 60 MCN the relative risk (RR) for developing MM increased 15 times compared to less than or equal to 10 MCN. Additional independent markers for an increased risk were presence of atypical MCN (RR = 7 vs. none) found in 45% of patients and in 5% of the control group, moderate to large numbers of actinic lentigines (RR = 6.2 vs. none), and lack of tanning as well as a tendency to sunburn (skin type I; RR = 2.2 vs skin type IV) No significant correlation was found between the relative risk for MM and hair color, eye color, duration of free time sun exposure and number of sunburns. Individuals with permanent outdoor profession and sun exposure, however, showed a clearly increased relative risk for developing MM.

Age Factors↗

[Epidemiology of malignant melanoma in West Germany in an international comparison].

The incidence and mortality of malignant melanoma (MM) has markedly increased in the Federal Republic of Germany. The data available show a doubling of incidence in the past 15 years and a doubling of mortality in the past 30 years. Germany holds a middle range in the incidence list of MM compared to worldwide data: 6-8 MM were registered per 100,000 inhabitants and year in Germany during the mid eighties, whereas 5 x higher incidences where reported from Australia and the southern states of the USA; incidences higher than 6-8/100,000 where found in the Scandinavian countries. While sun exposure is regarded as the most important risk factor in the international epidemiology of MM, a relationship between sun exposure and increasing risk of MM could not be clearly established for the German population. In contrast, the total number of melanocytic nevi (MCN) and the occurrence of dysplastic nevi where found to be significant markers of an increased relative risk for developing MM in the German population. The increase of the relative risk was 16 x for persons with greater than 60 MCN compared to individuals with greater than or equal to 10 MCN and there was an additional 7 x increase of the relative risk for persons with greater than or equal to 1 dysplastic nevus. The course of the disease is lethal in most cases of metastatic malignant melanoma. 90% of all patients in the Federal Republic of Germany, however, were first diagnosed in clinical stage I (= primary tumor alone) and the average 10 years survival rate was 70% in the time period since 1970. Multivariate regression analysis revealed that the most important prognostic factors in stage I MM were tumor thickness and sex. This finding should be taken into consideration for a prognostic classification of stage I MM.

Cross-Cultural Comparison↗

Change of epidemiological characteristics of malignant melanoma during the years 1962-1972 and 1983-1986 in the Federal Republic of Germany.

In the FRG data on more than 2,000 patients with malignant melanoma (MM) have been documented so far by the malignant melanoma cooperative group (MMCG 1962-1972) and by the central malignant melanoma registry of the German Dermatological Society (CMMR 1983-1988). In this study we compared the basic characteristics between these two multicenter data collections (CMMR until 1986) in order to detect any changes in clinical epidemiology of MM diagnosed within the past 20 years. The age distribution of the patients with MM at the time of first diagnosis did not reveal any change: a similar portion of patients was under 50 years of age (1962-72: males 44%, females 45%; 1983-86: males 44%, females 47%). The percentage of males with MM, however, increased in the CMMR group (35-41%) and the portion of tumors localized on the trunk was found markedly increased in both sexes (males: 39-56%, females: 15-25%). Comparison of the tumor thickness indicated some significant advance in the early recognition of MM: the percentage of thick tumors (greater than 1.5 mm) decreased between both time periods (males: 72-41%; females: 60-37%) with a corresponding elevation of thinner tumors. Nevertheless, during both time periods the first diagnosis was metastasizing melanoma in about 10% of all patients. Also, the proportion of prognostically unfavorable, nodular malignant melanomas remained nearly constant (about 30% of all patients in both groups).

Adult↗