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Biomedical subjects

H Hönigsmann

Publications and source records attributed to H Hönigsmann.

At least 127 records · Page 7Linked to original sources
PubMed1982

Serum levels of 8-methoxypsoralen in two different drug preparations: correlation with photosensitivity and UV-A dose requirements for photochemotherapy.

In a quantitative study we have compared the serum levels, the time course and the photosensitizing capacity of a conventional crystalline 8-methoxypsoralen brand and an investigational liquid formula. Evidence is presented showing that the liquid preparation is superior to the crystalline form: it peaks earlier after ingestion, it produces higher and more constant degree of photosensitization, it is eliminated more rapidly from the blood, and it requires a lower UV-A dose for eliciting photosensitivity reactions aiming at a reduction of the total cumulative UV-A dose required for clearing psoriasis.

Adult↗
PubMed1982

Selective accumulation of lipid within melanocytes during photochemotherapy (PUVA) of psoriasis.

In patients undergoing photochemotherapy (PUVA) a selective accumulation of lipid droplets was observed within the cytoplasm of melanocytes. Keratinocytes did not develop lipid droplets. Within 2 months after clearing of psoriasis the droplets gradually vanished and did not reappear even during maintenance PUVA therapy. Increased intracellular lipid deposits are usually taken to herald cell degeneration. Since the maximum lipid accumulation coincided with the end of the clearing phase when melanin production was at its height, the intramelanocytic lipid may have been a morphological sign of over-stimulation of melanocytes, which could eventually result in melanocyte destruction. Since excess melanin may be cytotoxic for melanocytes this may explain the irreversible hypopigmentation which develops in some patients treated with PUVA.

Adolescent↗
PubMed1981

Oral 8-methoxypsoralen photochemotherapy of psoriasis. The European PUVA study: a cooperative study among 18 European centres.

In a multicentre study in eighteen European cities 3175 patients were treated with photochemotherapy (PUVA) for severe psoriasis and data obtained during a period of 39 months were analysed. A response better than marked improvement was obtained in 88.8% of patients; twenty exposures and a total cumulative UVA dose of 96 J/cm2 were required for clearing, the duration of the clearing phase being 5.3 weeks. A comparison of the results of this study with those of a similar multicentre study in the United States on 1300 patients and using a different treatment protocol, revealed that while treatment results and the number of individual treatment sessions were similar the European protocol requires only half the time and less than half the total cumulative UVA dose for clearing of psoriasis. When patients in the European study who received continuous maintenance treatment were compared with patients who received no maintenance treatment the probability that a patient would remain in remission for a period of 80 weeks was the same, irrespective of whether patients received maintenance treatment or not. This study confirms the dramatic efficacy of PUVA in clearing psoriasis and contains two important messages for the reduction of possible long-term hazards of this treatment. Firstly, the total UVA energy requirements for clearing psoriasis strongly depend on the treatment schedule and can be kept low if an individual approach aimed at rapid clearing of psoriasis is used. Secondly, maintenance therapy may not significantly prevent recurrences for prolonged periods of time and may thus not be necessary in most patients.

Administration, Oral↗
PubMed1981

Ultraviolet light depletes surface markers of Langerhans cells.

This report defines the influence of ultraviolet light (UV) on Langerhans cells (LC). Human volunteers and hairless mice (Swiss ha/ha) were exposed to various single and/or cumulative doses of either UV-A, UV-B, or UV-A plus small amounts of UV-B (UV-A (+B)). 24 hr after the last irradiation, morphology of the entire epidermis was evaluated by both light and electron microscopy while LC, in addition, were tested for expression of specific histochemical (ATPase) and functional immunological markers (Ia antigens). In both men and mice, cumulative doses of either 80-120 J/cm2 UV-A (+B) or 1-2 X 100 J/cm2 UV-A resulted in a dramatic reduction of cells exhibiting ATPase and Ia-reactivity. In the UV-B spectrum, single doses of 60-80 mJ/cm2 produced a virtually complete elimination of LC membrane markers. By contrast, pemphigus antigens of keratinocytes were unaffected by these energy doses. Electron microscopy revealed cellular damage of some LC after UV-doses which produce a virtually complete abolition of LC membrane markers. At certain dose ranges (15-30 mJ/cm2 UV-B and 1 x 40 to 2 x 100 J/cm2 UV-A) LC were the only epidermal cells to display morphological damage at the ultrastructural level whereas higher doses affected all epidermal cells. The finding that LC surface markers and to a lesser extent the cells themselves are particularly susceptible to UV irradiation has important implications in view of previous findings that LC are potent stimulators of antigen-specific and allogeneic T cell activation. UV-induced alteration of LC plasma membrane integrity may represent a tool to manipulate adverse immune reactions involving the epidermis.

Adenosine Triphosphatases↗
PubMed1981

Unscheduled DNA synthesis in normal human skin after single and combined doses of UV-A, UV-B and UV-A with methoxsalen (PUVA).

The aim of this study was to measure unscheduled DNA synthesis (UDS) by autoradiography in normal human skin (I) after high dose UV-A, (2) after low dose UV-A applied before or after erythemogenic doses of UV-B, (3) after high dose PUVA and (4) after therapeutic doses of PUVA applied before and after erythemogenic doses of UV-B. Single high dose UV-A exposure induced roughly 60% of the amount of UDS induced by equally erythemogenic doses of UV-B. Single low dose UV-A exposure did not induce UDS, nor did it significantly alter the amount of UV-B induced UDS when combined with UV-B exposure. Single high dose PUVA did not lead to UDS and had no influence on UV-B induced UDS when combined with UV-B exposure. Our findings indicate: (I) erythemogenic doses of UV-A induce a considerable DNA excision repair; (2) low dose UV-A neither augments UV-B induced DNA repair nor does it inhibit the repair process; (3) no UDS was shown to occur after eight high or therapeutic doses of PUVA. This was unexpected since psoralen-DNA monoadducts have been shown to be repairable by a mechanism similar to excision repair of pyrimidine dimers. It is therefore assumed that PUVA as performed for therapeutic purposes either preferentially induced interstrand crosslinks not repairable via the classical repair mechanism or the repair of monoadducts was below resolution in this study; (4) therapeutic PUVA doses apparently do not interfere with excision repair of UV-B induced DNA lesions.

Adult↗
PubMed1980

Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients.

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.

Adult↗
PubMed1980

Diffuse melanosis in metastatic melanoma. Further evidence for disseminated single cell metastases in the skin.

Electron microscopy (EM) and electron microscopic cytochemistry have shown that diffuse melanosis in advanced metastatic melanoma is the result of an unlimited spread of single melanoma cells throughout the dermis; these cells retain their melanogenic capacity and continue to produce melanized melanosomes which eventually are deposited within dermal macrophages and thus impart to the skin a diffuse slate-blue color. These findings are in accordance with previous observations in a similar patient and thus support the concept that single cell metastasis represents a common pathogenic event in these patients.

Adult↗
PubMed1979

[Multilocular Paget's disease--a case report (author's transl)].

The simultaneous occurrence of Paget's disease in five different regions in a 76-year old woman is reported. Only one lesion exhibited the typical clinical appearance of this condition, whereas the others were diagnosed histologically. After radical surgical treatment of all lesions the patient has remained free from recurrence for more than three years.

Aged↗
PubMed1979

[Acute febrile neurophilic dermatosis (Sweet's syndrome)--report of two cases (author's transl)].

Acute, febrile, neutrophilic dermatosis (Sweeet's syndrome) is an uncommon, distinct disease of unknown origin. It is characterized by typical skin lesions and systemic symptoms such as fever and leucocytosis. Ultrastructural data suggest a primary vascular process as the initial pathogenic mechanism. In this paper two patients are described and the clinical variability, incidence and pathogenesis of this syndrome are discussed.

Adult↗
PubMed1979

Immunofluorescence demonstration of type IV collagen and a noncollagenous glycoprotein in thickened vascular basal membranes in protoporphyria.

Specific rabbit antibodies to type IV collagen isolated from a basement membrane producing mouse tumor were used in indirect immunofluorescence tests to study the thickened vascular basement membrane in skin biopsies from patients with erythropoietic porphyria (EPP) and from protoporphyric mice. In addition, rabbit antibodies to a noncollagenous, basement membrane specific glycoprotein also derived from the mouse tumor were tested. It was shown that normal as well as altered vascular basement membranes in both the human and the murine skin specimens react with the anti-type IV collagen and the antiglycoprotein antibodies. A particular strong reaction in the diseases skin indicated that formation of new vascular basement membrane layers involved deposition of the major structural proteins which also constitute normal basement membrane matrices.

Animals↗
PubMed1979

PUVA suppresses the proliferative stimulus produced by stripping on hairless mice.

Hairless mice were fed with 8-methoxypsoralen by gastric tube and exposed to UVA light to produce threshold phototoxic reactions. 3H-thymidine autoradiography revealed no significant difference of the epidermal labelling index as compared to that of nonirradiated animals (4.8 vs 6.2). Single PUVA exposures performed 2,8,14 and 24 hr after tape stripping lead to suppression of a wave of synchronized DNA synthesis present in nonirradiated control animals. These data demonstrate different reactions of stripped and unstripped epidermis to PUVA exposures and offer indirect evidence for the suppression of DNA synthesis in hyperproliferative skin disorders by PUVA in vivo.

Animals↗
PubMed1979

5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis.

5-Methoxypsoralen (5-MOP, Bergapten) was evaluated as a potential photosensitizing drug in oral photochemotherapy of psoriasis. Treatment results indicate that (1) 5-MOP is as effective as, and in high doses more effective than, 8-methoxypsoralen in clearing psoriatic lesions; (2) therapeutic doses of 5-MOP do not lead to erythema; the acute side-effects of 8-MOP PUVA therapy--erythema, blistering, pruritus--are thus avoided; (3) even high doses of 5-MOP are not followed by nausea. 5-MOP PUVA therapy thus represents a real alternative to 8-MOP PUVA, its advantages over 8-MOP PUVA being greater safety and patient acceptance.

Drug Administration Schedule↗
PubMed1979

Lichen planus and bullous pemphigoid.

A patient is described who had clinical and histopathological features of lichen planus and bullous pemphigoid; deposits of in vivo bound C3 at the basement membrane zone, which, at the electron microscopy level, were deposited in the lamina lucida; and with circulating IgG antibasement membrane zone antibodies which exhibited a pronounced C3 binding capacity. The similarity of our case to others described in the literature suggests that bullous lichen planus in fact represents the coexistence of two distinct diseases, namely lichen planus and bullous pemphigoid.

Adolescent↗