Psoralen bath plus UV-A therapy. Possibilities and limitations.
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Biomedical subjects
Publications and source records attributed to G Plewig.
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Iris nodules in neurofibromatosis I have become an important tool in the differential diagnosis of phakomatoses. The clinical appearance and importance of these nodules first recognized by Karl Lisch in Munich in 1937. The diagnosis and differential diagnosis of Lisch nodules are illustrated. The importance of iris nodules in genetic counselling of patients and their relatives is discussed, with emphasis on monosymptomatic cases. Histologically Lisch nodules are formed by aggregations of oval to round cells that form dome-shaped papules on the anterior layer of the iris. Immunohistochemically these cells are characterized by positive staining with antibodies against vimentin and S-100 protein. This proves their ectodermal differentiation. Thus Lisch nodules can be seen as a direct manifestation of neuroectodermal disturbances in neurofibromatosis I.
Introduced in 1979, isotretinoin remains a major advance in acne therapy. Both hospital- and community-based dermatologists have experience with this valuable drug, which, owing to its causal principle of action, offers a large proportion of patients the prospect of a cure. Isotretinoin is now in use in more than 80 countries and has been prescribed for some six million patients. Based on accumulated clinical findings with the drug, more comprehensive recommendations can now be made with respect to indications, dosing and duration of treatment than was possible when the drug was launched. Experience with the drug also provides a basis for reevaluating its safety profile. Finally, at a time when healthcare resources are limited, it is important to examine the cost-benefit ratio of this acne treatment versus other options. This paper is accordingly intended to provide a critical status report as well as a detailed and balanced set of recommendations for clinical practice.
BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. OBJECTIVE: Our purpose was to evaluate the efficacy of a combination of topical 5-fluorouracil twice a day and 20 mg of oral isotretinoin daily for disseminated actinic keratoses. METHODS: Twenty-seven patients who had disseminated actinic keratoses (3 women, 24 men) were treated with 5-fluorouracil (5%) twice a day applied to the photodamaged area bearing actinic keratoses along with oral isotretinoin, 20 mg daily. The median treatment time was 21 days. RESULTS: Actinic keratoses disappeared and signs of photodamaged skin improved in all patients. Side effects were burning and itching as well as painful erosions during the final stage of treatment. CONCLUSION: The combination of topical 5-fluorouracil and isotretinoin is highly effective in the treatment of disseminated actinic keratoses on photodamaged skin.
Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium-specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40-year-old woman with an 11-year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the grounds of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200-400 mg/day, led to a complete and long-lasting remission.
Approximately 20-50% of ultraviolet A (UVA) irradiation delivered to the skin surface may reach the human dermal microvascular endothelial cells (HDMEC) that play a pivotal role in cellular inflammatory tissue; however, the pathophysiologic role of HDMEC in UVA-induced skin changes is largely unknown. Based on previous in vivo and in vitro studies revealing UVA-induced expression of endothelial adhesion molecules, we studied isolated HDMEC under various conditions in order to further delineate the impact of UVA on these cells. The expression of cell adhesion molecules was determined by flow cytometry and the resulting changes of stable adhesion of leukocytes to endothelial cells were quantitated for granulocytes, lymphocytes, and monocytes using a newly developed multicellular adhesion assay. Additionally, antibody blocking experiments were performed to delineate the role of individual cell adhesion molecules in UVA-induced leukocyte adherence. High-dose polychromatic UVA (25 J per cm2, maximal emission at 375 nm) induced intercellular adhesion molecule-1 and E-selectin with different kinetics but correlating the adhesion of leukocyte subsets. This effect subsided, however, in the course of 3-6 daily applied UVA doses. Moreover, pro-inflammatory cytokine challenge by tumor necrosis factor-alpha and interleukin-1-alpha resulted in significantly weaker induction of intercellular adhesion molecule-1 and E-selectin in repeatedly UVA-exposed HDMEC. Differential quantitation of peripheral blood derived granulocytes, lymphocytes, and monocytes revealed reduced adhesion particularly of lymphocytes followed by monocytes and granulocytes compared with leukocyte adhesion to nonirradiated but cytokine-stimulated HDMEC. It is concluded that UVA substantially influences endothelial cell adhesion molecules expression and thus directly interferes with leukocyte adhesion to endothelial cells. Divergent UVA-induced effects in this respect can be attributed to the mode of UV exposure as well as to the condition of endothelial cells prior to UVA exposure.
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BACKGROUND AND OBJECTIVES: A Phase I dose-escalating trial with single doses of fozivudine tidoxil (BM21.1290; FZD), in vitro, and experimental in vivo data indicated that further investigations with this compound were warranted. Advantages of fozivudine tidoxil are the direct delivery of zidovudine monophosphate intracellularly and high concentrations in lymphatic tissues. Our objectives were to evaluate safety, tolerability and efficacy of fozivudine tidoxil in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: In a Phase I/II dose-escalating trial, three doses of fozivudine tidoxil (400, 800 or 1200 mg/day) were administered for 1 week. The study was randomized and placebo controlled. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. The exclusion criteria were active opportunistic infection and prior antiretroviral treatment. RESULTS: The tolerability of fozivudine tidoxil was excellent in all dose groups. No treatment discontinuations were necessary. Steady-state pharmacokinetics did show slightly higher concentrations as compared with levels after the first dose (20%). Viral load reduction was most pronounced in the 1200 mg/day dose group (-0.64 log). No viral load reduction was seen in the placebo group. CONCLUSIONS: The zidovudine conjugate fozivudine tidoxil is safe and well tolerated at the three doses tested. Based on the differences in molecular weights, the 1200 mg dose is roughly equivalent to 400 mg zidovudine.
Substantial subcutaneous haemorrhage without preceding trauma or underlying bleeding disorder is a rare occurrence in dermatological practice, essentially restricted to early childhood (acute haemorrhagic oedema of childhood). We report an adolescent with a morphologically unique bleeding manifestation. A 16-year-old boy presented with two episodes of massive subcutaneous haemorrhage in association with urticarial vasculitis. There was no history of preceding trauma or haemorrhagic disorder. Haemorrhage was observed in areas typically affected by angioedema, such as the periorbital, perioral, lingual, sublingual and laryngeal areas. History revealed an atopic diathesis with hay fever and examination showed alopecia areata. An antinuclear antibody titre and the presence of lupus anticoagulant indicated transient antiphospholipid antibodies. As urticaria corresponds to urticaria profunda angioedema, we hypothesize a pathophysiological relationship between superficial urticarial vasculitis and the deep variant of urticarial vasculitic disease, leading to the unique morphology present in our patient.
The aim of this investigation was to establish a new model for phototoxicity which is more advanced than the widely used cultures of yeasts, bacteria or cells of various origin, and at the same time to avoid animal testing. We studied the extraembryonal vasculature of the incubated hen's egg. This model was originally introduced by toxicologists as an alternative to the rabbit's eye irritation test (Draize test). In the photo hen's egg test, substances are applied to the embryo's yolk-sac blood vessel system at a non-toxic concentration and are irradiated with 5 J/cm2 ultraviolet A (UVA) (320-400 nm). Promethazine, haematoporphyrin, ciprofloxacin and 8-methoxypsoralen were tested in this system. Death of the embryo, membrane discoloration and haemorrhage are parameters for phototoxic damage, which were recorded during an observation period of 24 h. These well-known phototoxic substances induced pronounced damage of the yolk-sac membrane and blood vessels which was not found in the controls (test substance alone, UVA alone or untreated) using a 2 x 2 factorial test design. The photo hen's egg test serves as a valid screening model for substances supposed to be photosensitizers owing to a phototoxic mechanism.
Acne conglobata has been reported to be more common and more severe in XYY chromosomal aberration than in normal subjects. Whereas only exceptional cases have been observed in the more common XXY Klinefelter karyotype. We report a 17-year-old male with both Klinefelter's syndrome and acne conglobata, spreading from face to upper arms, trunk, buttocks and upper legs. The serum level of testosterone was normal, whereas luteinizing hormone and follicle-stimulating hormone were elevated. Skin lesions responded well to a combined therapeutic regimen including oral isotretinoin and prednisolone. An overview of severe acne in relation to chromosomal abnormalities is given and diagnostic and therapeutic options discussed.
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OBJECTIVES: To update information on endogenous retroviral sequences and discuss their role in systemic autoimmune disease. DATA SOURCES: Articles retrieved after MEDLINE search and personal communications and cooperation with the Institute of Virology. DATA SYNTHESIS: There are 2 modes of pathogenetic mechanisms through which endogenous retroviral sequences could cause systemic autoimmune disease: expression of endogenous retroviral gene products sharing antigenic determinants with cellular proteins; and activation or destruction of cellular genes as a consequence of insertional mutagenesis. Both mechanisms have been demonstrated in vitro and in vivo in animal models. CONCLUSION: Investigations on endogenous retroviral sequences in humans may offer new insights into the pathogenesis of autoimmune disease.
The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth-muscle actin was studied in fetal and adult hair follicles. The first stage of the developing hair follicle is characterized by palisaded, elongated epithelial cells budding from the epidermal basal layer. These cells express CK5/6, CK14, CK17, CK19, and vimentin. During the following weeks of gestation, different structures in the developing hair follicle can be identified and characterized. The matrical cells display only CK19. The keratinocytes of the outer root sheath express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath, CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen. The adult hair follicle in anagen fails to express CK19 in the matrical cells and isthmus and both CK17 and CK19 in the infundibulum. These profiles of intermediate filaments and other markers appear to be potentially useful in categorizing neoplasms with apparent follicular differentiation.
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