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Biomedical subjects

E W Breitbart

Publications and source records attributed to E W Breitbart.

At least 19 recordsLinked to original sources
PubMed2006

Effectiveness of information campaigns.

Skin cancer represents the most common type of cancer in the white population worldwide and the incidence has dramatically increased during the last decades. UV-radiation is believed to be the most important risk factor responsible for this trend. The prominent role of UV-radiation renders skin cancer most suitable for primary prevention, because the main risk factor can easily be avoided by sticking to simple rules for the behaviour in the sun or under artificial UV (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally especially due to the beneficial health effects of UV-irradiation like Vitamin D(3)-production, recommendations and information for the public should be as clear and as weighted as possible, through adequate messages, such as: "Love the sun and protect your skin". For that purpose the Association of Dermatological Prevention in Germany (ADP) developed the period of life programme (POLP) that defines certain age-specific target groups, with the aim to give well adapted prevention messages to the population during lifetime. Evaluation of primary prevention campaigns in Germany showed that due to continuous intervention programs during the last 16 years changes in the "sun-behaviour" of the population have been achieved leading to a reduced but sufficient exposure to solar UV-irradiation. This will then contribute to the aim of decreasing morbidity and mortality of skin cancer.

Attitude to Health↗
PubMed2003

[Prevention of skin cancer. Necessity, implementation and success].

Including malignant melanoma, basal cell carcinoma, and squamous cell carcinoma, skin cancer is the cancer with the highest incidence worldwide. Its incidence is increasing more rapidly than that of all other kinds of cancer. It is necessary to slow down this trend through preventive steps in order to reduce morbidity and mortality rates and to decrease the financial burden on the health systems. This goal could be achieved through primary (prevention of risk factors) and secondary prevention (early diagnosis and screening). This essay describes the necessity, realization, and success of these kinds of intervention programs. It especially portrays the procedures in Germany as they have been practiced for the last 15 years by the Society of Dermatology Prevention and German Cancer Aid.

Adolescent↗
PubMed2001

The velocity of ultrasound in human primary melanoma tissue - implications for the clinical use of high resolution sonography.

BACKGROUND: Ultrasonography with 20 MHz frequency can be used to estimate tumour thickness preoperatively in malignant melanoma (MM) of the skin. The vertical invasion depth is the single most important prognostic factor for localised MM, and its preoperative knowledge would be very useful for the planning of surgical procedures. Since ultrasonographic distance measurements directly depend upon the tissue specific ultrasound velocity, we determined the ultrasound velocity in primary melanoma. RESULTS: Ultrasound velocity was calculated from runtime differences of a 20 MHz ultrasound signal along a known distance either through water alone or through thick specimens of primary MM. The ultrasound velocities varied between 1553 m/s and 1588 m/s with a mean of 1564 m/s in four different MM specimens. The analysis of different parts of the specimens showed that the variation of the calculated velocities was larger between different specimens than within one individual specimen. CONCLUSIONS: The ultrasound velocity in MM tissue may be slightly lower than normally assumed, thereby explaining a part of the overestimation usually found in sonographic measurement of melanoma invasion depth. Additionally, the variation of ultrasound velocity between individual tumours may contribute to the impairment of the correlation found between sonometry and Breslow's measurement of MM invasion depth. For practical reasons, a setting of 1580 m/s will be appropriate for ultrasonography of primary malignant melanoma.

Biopsy↗
PubMed2001

Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage.

The distribution and persistence of cyclobutane pyrimidine dimers were investigated in mouse skin after chronic and acute exposures to ultraviolet-B radiation. We found that DNA damage accumulated in response to chronic irradiation and persisted in a unique set of epidermal cells located at the basal layer. Treatment with a tumor promoter caused the heavily damaged epidermal cells to divide and p53-immunopositive clusters to form within 24 h suggesting that these cells may be progenitors of the mutant p53 clusters associated with actinic keratoses and squamous cell carcinomas. In contrast to low fluence chronic irradiation, daily treatment with a higher fluence of ultraviolet-B produced extensive hyperplasia and considerably reduced penetration of photodamage. Exposure of chronically irradiated skin to an acute "sunburn dose" of ultraviolet-B also produced significant epidermal hyperplasia and resulted in complete loss of heavily damaged basal cells within 4 d postirradiation. The occurrence and distribution of cyclobutane dimers in human skin correlated well with putative sunlight exposure and resembled that observed in ultraviolet-B-irradiated mice. Heavily damaged basal cells were observed at various sites, including those receiving sporadic sunlight exposure, suggesting that these cells may play an important role in carcinoma formation in humans.

Animals↗
PubMed2000

Effects of whole-body UVB irradiation on cytokine production by peripheral blood mononuclear cells from stage I melanoma patients.

Ultraviolet (UV) radiation causes significant impairment of immunological function in human skin. The immunosuppressive effects of UV radiation are thought to be due to local release of cytokines by human keratinocytes, leading to impaired function of epidermal antigen-presenting cells (APC) and failure to induce cutaneous delayed-type hypersensitivity (DTH) reactions. Recent studies have shown that individuals susceptible to UV-induced suppression of DTH may be more prone to develop skin cancer including malignant melanoma (MM). Since the causal relationship between UV radiation and the induction of MM still seems obscure, we investigated the immunological reactions of peripheral blood mononuclear cells (PBMC) to whole-body irradiation with UVB in 15 stage I melanoma patients as compared to PBMC from normal volunteers matched for age, gender and skin type. Whole-body irradiation was performed with 0.8 minimal erythema dosages on five consecutive days. Peripheral blood was obtained before and after the procedure. Overall, there were no major effects of UVB irradiation on peripheral lymphocyte subsets and proliferation of PBMC from patients or normal controls, but UVB irradiation led to a significant increase in PWM-stimulated production of IL-6, IL-2R and TNF by PBMC. These changes were independent of the individual UVB dosages administered and appeared in both groups similarly. UVB irradiation did not lead to significant changes on IL-1 and IL-2 expression by PBMC. Our results suggest that PBMC participate in the cytokine response to UV, even in the absence of inflammatory reactions, but that this participation is not specific to MM patients.

Adult↗
PubMed2000

Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study.

The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94.5% (kappa 0.70, P < 0.0001). The kappa scores in different countries ranged from 0.65 to 0.77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

Adolescent↗
PubMed2000

The dose dependence of cyclobutane dimer induction and repair in UVB-irradiated human keratinocytes.

UVB and UVA components of the solar spectrum or from artificial UV-sources might be important etiological factors for the induction and development of skin cancer. In particular, deficiencies in the capacity to repair UV-induced DNA-lesions have been linked to this phenomenon. However, until now only limited data are available on the biological and physical parameters governing repair capacity. We have, therefore, developed a flowcytometric assay using fluorescence-labeled monoclonal antibodies to study the dose-dependence of induction and repair of UVB-induced cyclobutane pyrimidine dimers in a spontaneously immortalized keratinocytic cell line (HaCaT). Our results show that the kinetics of recognition and incision of UVB-induced DNA lesions slows down by a factor of about 3 in a dose range of 100-800 J m-2. Furthermore, a thorough analysis of repair kinetics indicates that this reduction in repair capacity might not be dependent on saturation of enzymatic repair capacity (Michaelis-Menten) but may be caused by a UV-induced impairment of enzymes involved in DNA repair. Because this effect is evident in vitro at doses comparable to the minimal erythemal dose in vivo, our results might have significant impact on risk assessment for UV-induced carcinogenesis.

Cell Line↗
PubMed1999

Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.

Animals↗
PubMed1999

Expression of complement regulator proteins in primary and metastatic malignant melanoma.

The expression of complement regulatory antigens C3b/C4b receptor, (CD35) membrane cofactor protein (CD46), decay accelerating factor (CD55), and homologous restriction factor 20 (CD59) was determined immunohistochemically on ten primary malignant melanomas, 16 metastatic lesions, and ten melanocytic nevi. All of the melanocytic nevi and 9/10 primary melanomas showed both expression of CD46 and CD59. In one primary melanoma lacking CD46, expression of CD35 could be detected. In metastatic melanoma, 9/16 metastases were CD46+/CD59+, two were CD46-/CD59+, one CD46+/CD59-, and four CD46-/CD59-. Additionally, CD55 could be detected in two CD46+/CD59+ metastases, and CD35 in one. Expression or lack of complement regulatory antigens did not correlate with the expression of GD2, GD3, HMB-45 or S-100. In conclusion, some cases of metastatic melanoma show loss of normal expression of complement regulatory proteins. This might have implications on the immune response or the efficacy of immune therapy in malignant melanoma.

Adolescent↗
PubMed1998

Fotemustine and interferon alpha2b in metastatic malignant melanoma.

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.

Adult↗
PubMed1997

Increased spontaneous formation of micronuclei in cultured fibroblasts of first-degree relatives of familial melanoma patients.

The phenomenon of spontaneous increased micronuclei and enhanced UV-sensitivity, which is known for familial cutaneous malignant melanoma (CMM) patients, could be demonstrated again in fibroblasts of 17 familial CMM patients. In order to determine if close relatives of familial CMM patients show both a comparable spontaneous chromosomal instability and enhanced UV-sensitivity, cultured fibroblasts of 24 healthy, first-degree relatives of patients with familial malignant melanoma were investigated. The cytokinesis-block micronucleous technique was used to detect enhanced chromosomal instability. Fibroblasts of the investigated relatives showed a significantly increased spontaneous formation of micronuclei, in comparison to 19 healthy controls, but no enhanced UV-sensitivity was evident. We conclude that chromosomal instability might be a hereditary trait and a causative factor in developing familial malignant melanoma. This supports the concept of a genetic predisposition to familial CMM and may help to identify high-risk family members at a cytogenetic level in addition to the common clinicopathological traits.

Adult↗
PubMed1997

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors↗
PubMed1997

Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.

Adolescent↗
PubMed1992

Fibroblast cultures of patients with basal cell epithelioma exhibit a normal sensitivity to the genotoxic effect of ultraviolet irradiation.

Fibroblast cultures of 16 basal cell epithelioma (basalioma, BCE) patients with an unusually young age at onset of disease (29-51 years; 42.5 +/- 7.04), and healthy normal controls (27-55 years; 40.73 +/- 9.52) were studied for chromosome instability induced by ultraviolet rays (UV). We used an UV source that emitted predominantly UV-A and UV-B at an intensity of 375 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). Young basalioma patients and normal controls showed no significant differences in MN and SCE frequencies, neither with respect to spontaneous nor to UV-induced values (MN spontaneous: 10.80 +/- 5.65 vs. 11.32 +/- 8.21; UV-induced increase: 7.36 +/- 4.40 vs. 9.93 +/- 7.55; SCE spontaneous: 10.28 +/- 1.61 vs. 10.72 +/- 1.09; UV-induced increase: 7.30 +/- 2.19 vs. 7.55 +/- 2.14). We conclude from these data that an enhanced UV sensitivity as observed in cells from patients with cutaneous malignant melanoma and xeroderma pigmentosum is not a constitutive risk factor in basalioma patients.

Adult↗
PubMed1992

Increased mutagen sensitivity in human cultured fibroblasts with constitutively high micronucleus levels.

The induction of micronuclei (MN) by incubation with different mutagenic agents was tested in diploid fibroblast cultures obtained from 15 probands with constitutively high MN rates (15.75-77.25 MN/500 cells; average 36.27 +/- 17.60 MN) and 15 probands (controls) with low MN rates (4-13.75 MN/500 cells; average 8.97 +/- 2.73 MN). In order to find out whether fibroblast cultures of individuals with increased spontaneous MN levels exhibit an increased sensitivity to various agents with different genotoxic mechanisms, we studied the induction of MN in these cell cultures by ultraviolet (UV) irradiation, mitomycin C (MMC), N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and benzo-(a)pyrene-diol-expoxid (BPDE). In addition, we tested aphidicolin (APC), a polymerase alpha inhibitor, which is a potent inducer of common fragile sites. Probands with spontaneously high MN showed an significantly increased sensitivity to UV (p less than or equal to 0.005), MMC (p less than or equal to 0.005), and BPDE (p less than or equal to 0.005). No significant differences were found for MNNG and APC as compared to controls.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

[Dermatoglyphic diagnosis in patients with atopic eczema].

The purpose of this investigation was to find out whether the new Dermalog system could be used in conjunction with dermatoglyphics in patients with atopic dermatitis. For this purpose, 92 patients with atopic eczema (58 women and 34 men) were examined and were compared with two different control groups. The first control group, representing the normal population, consisted of 100 female and 100 male randomly selected subjects. The second control group (55 women and 24 men) excluded any persons with a history of atopic syndrome. First of all, hand and fingerprints were taken. The data were stored in a computer and were statistically analysed with the aid of significance and discrimination tests. Evaluation of the patients' data showed no significant difference from the first control group. Results in the second, selected, control group were better. For example, in this group, in which the probability was 93.1%, 76.4% of the women examined were found to have atopic dermatitis. The probability among the male patients examined was 99.9% and the corresponding sensitivity, 77.0%.

Adolescent↗