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Biomedical subjects

F Gschnait

Publications and source records attributed to F Gschnait.

At least 145 records · Page 8Linked to original sources

Photochemotherapy for pustular psoriasis (von Zumbusch).

Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1 1/2 years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy.

Adolescent↗

[Oral photochemotherapy (author's transl)].

Photochemotherapy (PUVA) with oral administration of the photosensitizer 8-methoxypsoralen and irradiation with UVA light has become a proved method for the therapy of psoriasis. The treatment is based upon repeated PUVA exposures, which are monitored by exact dosimetry within the desired therapeutic ranges. The present study, which covers an observation period of 3 years, is engaged with the practicability of the PUVA method for the treatment of the various forms of psoriasis, mycosis fungoides, atopic eccema and lichen planus, and, on the other hand, with its side effects and potential long term hazards. Photochemotherapy was shown in clinical routine as an highly effective treatment, which lead to complete clinical remission in all diseases investigated. By maintenance treatment patients with psoriasis could be kept in remission even for long periods of time. Following the dosage parameters toxic side effects were rare and reversible. Histological, histochemical and ultrastructural investigations showed no alteration of skin under photochemotherapeutic conditions. Experimentally induced massive PUVA overdosage, however, led to damage of epidermis and corium and to long lasting benign changes of the melanin pigment system. To study potential long term side effects (hepatotoxicity of 8-methoxypsoralen, cataract formation, development of degenerative or hyperplastic skin changes and disturbances of the immunologic reactivity) laboratory investigations, histologic, ophthalmologic and immunologic studies have been performed. During an observation period of up to 3 years no evidence of long term side effects was found.

Adult↗

[Photochemotherapy for psoriatic patients treated with corticosteroids and methotrexate].

The effect of photochemotherapy with oral administration of 8-methoxypsoralen followed by irradiation with UVA (PUVA) was investigated in 34 cases of severe, generalized psoriasis which could be controlled only by systemic administration of corticosteroids and cytotoxic agents. In each case clearing of psoriatic lesions was achieved under PUVA treatment. As expected, the average duration of the initial PUVA treatment period was longer when compared to patient groups not pretreated with corticosteroids and cytotoxic agents. In order to avoid relapses, maintenance treatment was installed after complete healing of psoriatic lesions comprising an average of one PUVA exposures per week. Eighty percent of such treated patients are continuously completely clear; the remaining patient group is 70--90% improved. The side effects, elicited by the previous administration of corticosteroids and/or cytotoxic agents are improved or have resolved under PUVA therapy. The present study indicates, that PUVA treatment of psoriasis is not only an alternative to the use of systemic corticosteroids and cytotoxic agents but is superior to these treatment modalities due to its lack of side effects and its higher effectiveness.

Adrenal Cortex Hormones↗

The pigmentary response to photochemotherapy.

Previous studies on skin topically photosensitized with trimethylpsoralen and subsequently irradiated with long-wave UV light have demonstrated an increase in melanosome size and changes in the distribution patterns of melanosomes, suggesting the possibility of gene derepression or the induction of a somatic mutation of melanocytes. The present investigation was performed to determine whether identical changes are induced by systemic photochemotherapy using 8-methoxypsoralen and UVA (PUVA) under therapeutic conditions. Our results show that PUVA stimulates melanogenesis but does not induce significant changes in the average size of melanosomes nor in their distribution patterns within keratinocytes. Thus they indicate that under therapeutic conditions PUVA does not induce morphologically detectable cytogenetic changes in pigment cells.

Adult↗

Mouse model for protoporphyria. III. Experimental production of chronic erythropoietic protoporphyria-like skin lesions.

Albino mice were made protoporphyric with griseofulvin according to an established procedure. Photosensitivity flares were elicited once a week throughout a 10-month period, using black light as a source for 410 nm radiation and the flares were monitored by the intravenous injection of vascular tracers and by light and electron microscopy. Each irradiation led to a selective destruction of the endothelial cells of superficial capillaries which was followed by massive vascular leakage. The basal lamina remained largely intact, providing the scaffold for regenerating endothelial cells which deposited new basal lamina material at their periphery. Subsequent exposures to 410 nm radiation reproduced the endothelial damage and subsequent basal lamina formation; multiple irradiations thus resulted in excessive, concentric, tubelike basal lamina deposits around dermal vessels which light microscopically appeared as PAS-positive hyaline material and clinically gave the skin a thickened, waxy appearance. This model thus reproduced the skin of erythropoietic protoporphyria clinically, microscopically, and at the ultrastructural level.

Animals↗

Protective action of beta-carotene against lethal photosensitization of fibroblasts in vitro.

Cell culture experiments using haematoporphyrin photosensitized bovine hoof fibroblasts and long-wave uv-irradiation revealed two distinct and separable patterns of lethal photosensitization according to two different sensitization procedures: (1) Photosensitization of cell membranes by short exposure (5 min) of cells to haematoporphyrin. (2) Cytoplasmic photosensitization elicited by a 2 h exposure of cells to haematoporphyrin. Cell membrane photosensitization was reversible by incubation of cells in serum which removed surface bound haematoporphyrin; cytoplasmic photosensitization was irreversible. Beta-carotene was tested in these two systems and the following results were obtained: (1) Preincubation of bovine hoof fibroblasts in beta-carotene protects from lethal haematoporphyrin photosensitization. (2) Protection with beta-carotene is achieved against both types of photosensitization. (3) The protective effect of beta-carotene depends upon the duration of pretreatment, reaching a maximum after 7 days. (4) Beta-carotene protection is maintained even after trypsinization of bovine hoof fibroblasts and withdrawal of beta-carotene from the medium for 24 h or more. (5) Haematoporphyrin sensitized bovine hoof fibroblasts show a distinct pattern of red fluorescence for each type of photosensitization. Incubation of bovine hoof fibroblasts in beta-carotene prior to haematoporphyrin photosensitization results in a pronounced reduction of red fluorescence. Some of these data indicate that beta-carotene acts, at least in cell membrane photosensitization, at the level of the cell membrane into which it appears to be incorporated.

Animals↗

Experimental induction of hepatocellular hyalin (Mallory bodies) in mice by griseofulvin treatment. 1. Light microscopic observation.

Griseofulvin (GF) feeding of mice resulted in protoporphyria, liver cell damage, bile duct alterations, and finally hepatoma formation. In addition, hepatocellular hyalin developed, resembling in its morphology classic Mallory bodies (MB) as seen in alcoholic and nonalcoholic liver disorders in man. Liver cells containing MB often displayed features of severe cell damage and MB were finally released into the sinusoids and degraded by macrophages. The rapid disappearance of MB following GF discontinuation and the reappearance after resumption of GF feeding suggest an intimate relationship between metabolic alterations in the hepatocytes exerted by the drug and MB formation. This assumption is further supported by the fact that MB change their tinctoreal properties in chromotrope aniline blue-stained sections after GF discontinuation, possibly relfecting degeneration. Long term GF treatment apparently primed the liver for MB formation since the cells were able to respond almost instantly with MB to a GF challenge after a 1-month GF-free period.

Animals↗

Photochemotherapy for psoriasis with orally administered methoxsalen.

Photochemotherapy denotes a therapeutic approach that is based on the interaction of light and a photoactive drug. This study describes the efficacy of photochemotherapy, using orally administered methoxsalen and long-wave ultraviolet light in 91 patients with severe, generalized psoriasis. Oral administration of methoxsalen was followed by exposure to a high-intensity long-wave ultraviolet light source, emitting a continuous spectrum between 320 and 390 nm (peak, 365 nm) and an energy of 5.6 to 7.5 mw/sq cm at 15 cm. There was complete clearing of 82 patients (90%), a 90% to 100% clearing in seven (8%), and a satisfactory improvement in two (2%). A paired comparison study in 54 patients showed photochemotherapy to be far more effective than ultraviolet light emitted by fluorescent bulbs or a xenon source. Eighty-five percent of the patients receiving outpatient maintenance treatment have remained in remission for periods up to 400 days.

Administration, Oral↗

[Photochemotherapy of psoriasis: clinical experiences with 152 patients (author's transl)].

Photochemotherapy, a recently developed method of treatment, is based on the effect of light on a systemically administered photo-active substance. 152 patients with severe generalized psoriasis were exposed, after oral administration of 8-methoxy-psoralen, to a high-intensity UVA light source radiating at a continuous spectrum between 320 and 390 nm (maximum at 365 nm). Radiation doses ranged from 1.4 to 4.8 J/cm2 and were progressively increased. Complete remission occurred in 141 patients, satisfactory improvement in the remaining 11. It required 12+/-6 radiation sessions (-/x +/- s) to obtain remission, mean duration of treatment being 22 +/- 14 days. Apart from a neutral ointment no other local or systemic therapy was used. Photochemotherapy completely healed the psoriatic foci leaving evenly tanned, cosmetically appealing skin. All patients were treated at intervals as out-patients (average once a week or ev-ry other week), and remained without recurrence for up to 400 days. No local treatment is required with photochemotherapy, which is very effective, simple, harmless and does not stress patient or doctor. Interval treatment maintained the cure.

Adolescent↗

Mouse model for protoporphyria. I. The liver and hepatic protoporphyrin crystals.

Outbred albino mice were rendered protoporphyric by a diet containing 2.5% (weight) of griseofulvin. There was a 5-fold increase in liver weight, hepatocellular degeneration and necrosis, cholestasis, ductular proliferation and cirrhosis. Liver protoporphyrin values were elevated and brown pigment granules were present in hepatocytes, Kupffer cells, and bile ducts. The granules showed red fluorescence, birefringence, and, at the ultrastructural level, consisted of aggregates of needle-like crystals. Crystals isolated from such livers showed solubility and absorption characteristics of protoporphyrin; in vitro recrystallization of protoporphyrin, extracted from protoporphyric mouse livers, yielded crystals identical with those observed in vivo, and commercial protoporphyrin exhibited similar morphologic features. The liver pathology and protoporphyrin crystals observed in these animals are identical to the liver pathology and crystals observed in the human disease, erythropoietic protoporphyria. In this mouse model, protoporphyrin crystals are intimately associated with hepatocellular injury and it appears that their accumulation within hepatocytes leads to hepatocellular destruction. A similar pathogenesis is postulated for the hepatic damage that occurs in some cases of erythropoietic protoporphyria.

Animals↗

Mouse model for protoporphyria. II. Cellular and subcellular events in the photosensitivity flare of the skin.

Acute phototoxic reactions were induced by long-wave ultraviolet light (UV-A) in mice with griseofulvin-induced protoporphyria. The clinical response was characterized by erythema, pronounced edema, and purpura. Tracer experiments and electron microscopy revealed pronounced vascular damage and leakage of vascular contents, whereas the epidermis and all other dermal components were intact. There was selective destruction of endothelial cells and damage of the basal lamina of the vessels. This striking vascular injury was absent from nonprotoporphyric UV-A-irradiated mice and from protoporphyric and nonprotoporphyric mice exposed to short-wave ultraviolet light (UV-B). Patients with erythropoietic protoporphyria (EPP) exhibit an identical, selective damage of blood vessels when irradiated with UV-A or sunlight but not with UV-B alone. It is hypothesized that in both murine protoporphyria and EPP, endothelial cells are photosensitized by protoporphyrin circulating in the serum and that photosensitized endothelia represent the primary cellular target of the photochemical reaction induced by UV-A.

Animals↗

Hepatocellar hyalin (Mallory bodies) in long term griseofulvin-treated mice: a new experimental model for the study of hyalin formation.

Experimental studies on the significance and origin of hepatocellular "alcoholic" hyalin (Mallory bodies) are hampered by the lack of a suitable animal model. In the present paper, the experimental production of hepatocellular hyalin identical with human alcoholic hyalin both light and electron microscopically in long term griseofulvin-treated mice is described. Moreover, the results conclusively disprove the specificity of Mallory alcoholic hyalin for alcohol-induced liver cell damage.

Alcoholism↗