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Biomedical subjects

E Breitbart

Publications and source records attributed to E Breitbart.

17 recordsLinked to original sources

[The educational program for the management of psoriasis vulgaris according to the rules of the Task Force on Dermatological Prevention: current status].

BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease with a substantial impairment of quality of life. Interdisciplinary outpatient educational programs are an innovative supplementary therapy form for the management of this disorder. SUBJECTS AND METHODS: The Task Force on Dermatological Prevention developed a concept for outpatient instruction of psoriasis patients. Five 2-hour classes by dermatologists, psychotherapists/psychologists and dieticians focus on central topics relevant for the patients and the management of the disease. RESULTS: The results presented are based on own experiences with this educational program. The interdisciplinary program is accepted very well and seen as helpful by the concerned. A structure analysis of the effects in a greater number of cases is a current goal. In some areas, health insurance companies are paying for the classes. CONCLUSION: The educational program for the management of psoriasis vulgaris according to the rules of the Task Force on Dermatological Prevention is a supplement of the treatment of patients with this chronic skin disease. Broader implementation in Germany is desirable.

Ambulatory Care↗

Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury.

Doxorubicin (DOX) produces clinically restorative responses in numerous human cancers, but its cardiotoxicity has limited its usefulness. Because reactive oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, we evaluated the prophylactic effect of spinach natural antioxidant (NAO) on DOX-induced cardiotoxicity and oxidative stress in female Balb/c mice using histological, electron microscopical and biochemical parameters. Mice were treated with NAO for 7 days prior to and/or for 6 days after DOX administration. Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hinder the effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed myocardial degeneration. When administered combined before and after DOX, NAO conferred the most significant cardiac protection. The effects of NAO on the lipid peroxidation product, malondialdehyde, and on H2O2/ hydroperoxides were examined on day 6 following DOX administration; levels of both were elevated in DOX-treated mice, compared to control. Pretreatment with NAO prevented these changes. Pretreatment with NAO before DOX administration decreased catalase and increased superoxide dismutase activities compared to the DOX group. Our results suggest usage of NAO in combination with DOX as a prophylactic strategy to protect heart muscle from DOX-induced cellular damage.

Animals↗

Combined treatment of stage IV melanoma patients with amifostine and fotemustine--a pilot study.

Amifostine (Ethyol) is a new chemoprotective agent that has been shown to have significant activity in the prevention of nephro-, oto-, neuro- and haemotoxicity. In preclinical models as well as in clinical trials carried out in patients suffering from various malignancies, the adverse effects and signs of toxicity related to a number of cytostatic drugs, including cisplatin, cyclophosphamide, carboplatin and mitomycin C, were prevented. In Europe fotemustine (Muphoran) is widely used in the treatment of brain metastases in melanoma patients. However, the dose is often limited by severe bone marrow toxicity after induction cycles, particularly in heavily pretreated patients. In order to test whether amifostine treatment might promote bone marrow protective effects when combined with fotemustine chemotherapy, we conducted a preliminary study in 10 patients suffering from stage IV disseminated malignant melanoma. The patients received amifostine (740 mg/m2) prior to fotemustine chemotherapy (100 mg/m2). Six of the patients had failed one or two other prior chemotherapy regimens. Seven patients had brain metastases. Among the 10 patients treated with amifostine and fotemustine, no major clinical responses (complete response or partial response) were achieved, with four patients showing stabilization of the disease over more than 3 months. No patient in the amifostine plus fotemustine treatment group showed severe myelosuppression (WHO grade III/IV), in contrast to a historical control group treated with fotemustine alone, in which about 40% developed major thrombocytopenia and about 45% developed severe leucopenia (WHO grade III/IV). Therefore, we conclude that the combination of amifostine with fotemustine was well tolerated in this small series of patients and further studies are warranted to test the amelioration of myelosuppression by the addition of amifostine.

Amifostine↗

[Perianal ergotismus gangraenosus].

Ergotamine-containing drugs are widely used in the treatment of acute migraine attacks. Among others, spastic vasoconstrictions are one of the possible side effects usually affecting the lower extremities and sometimes leading to gangrene. The case of a 75 year old woman is presented who was suffering from migraine-attacks since adolescence. Due to longterm use of ergotamine containing suppositories she developed perianal ulcers. After withdrawal of the drug the ulcers healed up entirely. The spectrum of ergotamine-induced side-effects and possible intervention strategies are discussed.

Aged↗

The effect of retinol and retinoic acids on lipoxygenase activity.

Lipoxygenase catalyzes the dioxygenation of polyenoic fatty acids such as linoleate and arachidonate. The aim of the present study was to examine the effect of retinol, all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid. Lipoxygenase activity toward linoleic acid was followed by determining changes in absorption at 234 nm. All retinoids inhibited lipoxygenase-1 and lipoxygenase-2 activity. Lipoxygenase-2 activity towards linoleic acid was rapid at pH 6.5; all-trans-retinol (10 microM) caused a 50% inhibition in reaction rate. All-trans-retinol was oxidized in parallel with diene production by lipoxygenase-2. Lipoxygenase-2 activity on linoleic acid was competitively inhibited by all-trans-retinol and all-trans-retinoic acid; 13-cis-retinoic acid exhibited mixed type inhibition. Activity of lipoxygenase-1 towards linoleic acid at pH 9.0 was also inhibited by retinoic acids by 32-73%. All-trans-retinoic acid and 13-cis-retinoic acid inhibited lipoxygenase-1 activity competitively, whereas all-trans-retinol inhibited lipoxygenase-1 activity in a mixed manner. These findings suggest that retinoids may bind to the active site of the enzyme or simultaneously act as an antioxidant.

Binding Sites↗

Lipoxygenase activity in heart cells.

Arachidonic acid (AA) metabolism via the lipoxygenase (LOX) pathway in rat hearts and in cultured rat cardiomyocytes was investigated using 1-[14C]AA. LOX activity was detected in the microsomal fraction, in the high speed supernatant prepared from rat hearts and in rat cardiomyocyte supernatant. LOX products from all fractions comigrated in thin layer chromatography as 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE. Enzyme linked immunosorbent assay for 12-HETE showed its formation by the microsomal fraction, the ammonium sulfate (AS) pellet, and by rat cardiomyocyte supernatant, while radioimmunoassay for 15-HETE showed its formation only by the AS pellet. The properties of LOX in each fraction are reported here.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Studies on cultured fibroblasts from patients with cutaneous malignant melanoma.

Cultured fibroblasts from patients with cutaneous malignant melanoma (CMM) were tested for chromosomal instability by determination of micronuclei (MN) and sister chromatide exchange (SCE). The constitutive as well as the UV-induced level of MN was increased in CMM patients, being most pronounced in the familial cases. There was an increased UV sensitivity in CMM by using SCE, but no spontaneously enhanced SCE value. The enhanced UV sensitivity in CMM patients was in a comparable range as those of XP heterozygotes. We thus conclude that chromosomal instability is a concurrent feature of a genetic predisposition for CMM.

Cells, Cultured↗

Increased numbers of spontaneous micronuclei in blood lymphocytes and cultures fibroblasts of individuals with familial cutaneous malignant melanoma.

In vitro detection of micronuclei was used to determine spontaneous chromosomal instability in cultured fibroblasts of 28 healthy normal controls, 28 individuals with nonfamilial cutaneous malignant melanoma (CMM) and 14 people with familial occurrence of CMM. Lymphocytes from 40 healthy controls, 40 CMM patients and 6 individuals with familial CMM were also compared for spontaneous expression of micronuclei in vitro. In the familial cases micronucleus frequency was found to be higher, both in cultured fibroblasts (P less than 0.005) and in lymphocytes (P less than 0.001) as compared to normal controls. There was no significant difference between nonfamilial cases and normal controls. We conclude that chromosomal instability may contribute to a genetic risk for development of cutaneous malignant melanoma.

Adult↗

Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum.

Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 +/- 1.96 vs. 1.82 +/- 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 +/- 3.49 vs. 9.01 +/- 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients.

Cells, Cultured↗

Malignant melanoma--its precursors and its topography of proliferation. DNA-Feulgen-cytophotometry and mitosis index.

DNA-content and size of the nuclear areas in different zones of malignant melanomas of different histological types and in dysplastic naevi were measured in order to provide information on the histogenesis and proliferative behaviour of human malignant melanoma. The results were compared with those from normal epidermis, common naevi, and reactive melanocytic hyperplasias. The mitotic index of melanomas--divided into different topographic zones in an analogous way--was also determined. The DNA-histographs of all naevi and reactive melanocytic hyperplasias showed a diploid maximum, but the dysplastic naevi had a larger proportion of nuclei with hyperdiploid and tetraploid DNA-content, indicating an increased proliferative activity. The mean values (X) of nuclear areas in dysplastic naevi (DN) were about the same as in common naevi (CN) and slightly lower than in superficial spreading melanomas (SSM). The coefficient of variability (cv) as an indicator of anisokaryosis was markedly higher in DN (27.8) and SSM (29.3) than in CN (20.2). In DNA-content we found similar results: almost no difference in mean values, but DN taking an intermediate position between CN and SSM with respect to cv (CN: 12.3; DN: 21.0; SSM: 36.6). There was no unequivocal evidence in these data for DN being a precancerous stage. Superficial melanomas with a nodular component ("SSM/NM") differed from SSM and NM by increased DNA-content and greater variability of nuclear areas and showed the clearest features of malignancy in their DNA-histographs. The mitotic indices had rather low values in SSM and intraepidermal marginal zones of "SSM/NM" on one hand and markedly higher values in NM and nodular parts of "SSM/NM" on the other. The highest mitotic counts were found in the three investigated metastases.

Cell Cycle↗

Malignant melanomas contain only the vimentin type of intermediate filaments.

Six malignant melanomas have been examined for the type of intermediate filament they contain. All six cases showed positive staining of intermediate filaments with antibodies to vimentin, with cells containing large numbers of melanosomes being stained less strongly in general. The tumor cells did not react with antibodies to keratin, desmin, neurofilaments or glial fibrillary acidic protein. Thus typing of intermediate filaments can distinguish melanoma from undifferentiated carcinoma, but not from lymphoma or sarcoma. Since melanocytes are known to be vimentin positive, and since most of the samples we studied were from metastases, these results are a further indication that the intermediate filament type typical of the parental cell is retained in the metastases, as well as in the primaries of solid tumours. The implications of vimentin positivity for the histiogenesis of the melanocyte are also discussed.

Cytoskeleton↗

[Surgical treatment of skin changes in cutis laxa (author's transl)].

Cutis laxa is an extremely rare genetic disorder of connective tissue. The striking dermatologic features are loose skin folds and skin laxity. Due to these folds the patients appear to be prematurely aged. Plastic surgery can improve these changes. This treatment is especially indicated in patients with the autosomal dominant type of cutis laxa where internal manifestations do not occur. We report the case of a seventeen years old boy with cutis laxa and surgical therapy.

Adolescent↗