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Biomedical subjects

B Ortel

Publications and source records attributed to B Ortel.

At least 55 records · Page 3Linked to original sources
PubMed1992

Middermal elastolysis in an elderly man with evidence of elastic fiber phagocytosis.

BACKGROUND: Middermal elastolysis is a clinically and histologically distinct entity. This idiopathic loss of dermal elastic fibers has mostly been reported in younger adults. To our knowledge, the present case, which has been followed up for 4 years, is the first to occur in an elderly man. OBSERVATIONS: Two years after the onset of progressive wrinkling of the upper aspect of the thorax, the patient underwent a biopsy. Histologic examination of the specimens confirmed previous findings of middermal elastolysis. Examination of extracutaneous elastic tissue showed normal findings. Electron microscopy demonstrated elastic fibers embraced by macrophages, which is suggestive of elastic fiber phagocytosis. For the following 4 years, the patient has remained in stable clinical condition. CONCLUSIONS: Middermal elastolysis is probably more common than has been assumed so far. It does not affect nondermal elastic tissue. After progressive loss of dermal elasticity in a circumscribed area, a benign course follows, with a stable condition over several years. Electron microscopic findings indicate that elastic fiber phagocytosis is operative in the disappearance of the middermal elastic tissue.

Aged↗
PubMed1991

Relative efficacy of 335 and 365 nm radiation in photochemotherapy of psoriasis.

The action spectrum for the induction of phototoxic erythema by treatment with 8-methoxypsoralen (8-MOP) and UVA peaks at around 335 nm. Because earlier investigations reported peak phototoxic activity at 365 nm, we compared the antipsoriatic efficacy of 335 and 365 nm in an oral psoralen photochemotherapy (PUVA) regimen using a monochromator. PUVA with 335 nm was twice as effective as with 365 nm, with respect to both erythemogenicity and the cumulative dose required for clearing psoriasis. However, 335 and 365 nm were equally effective if delivered in equal erythema doses. It appears that in human skin the antipsoriatic activity of 8-MOP parallels its erythemogenicity.

Dose-Response Relationship, Radiation↗
PubMed1991

Long persistence of monofunctional 8-methoxypsoralen-DNA adducts in human skin in vivo.

Human skin can be persistently photosensitized by topical application of aqueous 8-methoxypsoralen plus immediate irradiation with a non-erythemogenic dose of wavelengths above 380 nm. Re-exposure of skin thus sensitized to broadband UV-A produces phototoxic erythema 72-120 h later. The persistence of the photosensitization was demonstrated by phototoxic erythema after re-exposure up to 15 days after the first sensitizing irradiation. According to the concept that the first exposure induces primarily psoralen monoadducts, we consider this an investigation of psoralen monoadduct persistence. In contrast to several earlier studies, this sensitive method indicates that psoralen monoadducts may remain in human skin in vivo for more than 2 weeks after formation.

DNA↗
PubMed1990

Investigations of a manganese-containing mimic of superoxide dismutase in riboflavin phototoxicity in human cells in vitro.

The activity and specificity of a manganese-containing low molecular weight mimic of superoxide dismutase (manganese desferioxamine (Mndf)) were investigated in riboflavin (Rf) photosensitization in solution and cell culture. In addition to the very high superoxide dismutase-like activity of Mndf at micromolar concentrations, photochemical studies in solution indicated that it could quench excited singlet and triplet states at millimolar concentrations. Human erythrocytes, human lymphocytes and a human bladder carcinoma cell line were used to evaluate the potential of Mndf for in vivo use. The efficacy and toxicity of Mndf in the protection against Rf photoxicity varied between the different cell types.

Deferoxamine↗
PubMed1990

An action spectrum for the elicitation of erythema in skin persistently sensitized by photobound 8-methoxypsoralen.

Human skin can be rendered persistently photosensitive by topical application of aqueous 8-methoxypsoralen (8-MOP) and exposure to a suberythemogenic dose of more than 380 nm radiation. We report an action spectrum for the elicitation of phototoxic erythema induced by a second exposure of skin pretreated in this way. After correction for unsensitized skin erythema this action spectrum resembles the absorption spectrum of the 4',5'-monoadduct of 8-MOP to DNA. This suggests that the monoadduct is the chromophore for erythema elicited by the second irradiation, and supports the DNA crosslink as the crucial photoproduct causing phototoxic erythema due to 8-MOP in human skin.

Differential Threshold↗
PubMed1989

Photosensitizing compounds in the treatment of psoriasis.

Photosensitizers were first used to treat psoriasis 15 years ago when the phototoxic reaction of psoralens and UVA was found to induce remissions of the disease. The effect of this reaction on DNA, particularly the formation of cross-links, was thought to be the decisive event. Strong cross-linking agents such as 8-MOP, TMP and 5-MOP are clinically effective whereas most compounds which produce only monofunctional adducts are virtually ineffective. Orally administered 8-methoxypsoralen (8-MOP) is the most widely used compound. 4,5',8-Trimethylpsoralen (TMP) is poorly absorbed from the intestine but has marked efficacy when applied topically. 5-MOP may be a useful alternative to 8-MOP because it is less erythemogenic and does not cause nausea. These three furocoumarins appear to be similar photochemically and may introduce similar risks. However, the photobiological properties of furocoumarins can be modified by altering one or more parts of the molecule. Such modifications might yield effective analogues with reduced cytogenetic hazards. Several psoralens and angular furocoumarins are being tested for effectiveness combined with fewest long-term side-effects, especially carcinogenesis. Encouraging preliminary results have been obtained with 7-methyl-pyridopsoralen and 4,6,4'-trimethylangelicin. Other important approaches to increasing the safety of photochemotherapy may be the use of different photoactivating wavelengths or the introduction of new classes of photosensitizers.

Humans↗
PubMed1989

Photosensitivity and hyperpigmentation in amiodarone-treated patients: incidence, time course, and recovery.

Amiodarone (AD) induces photosensitivity in 75% of the patients treated with this drug. Phototoxic reactions can be experimentally elicited with UVA but not with UVB. The UVA-MED is significantly reduced after 12 months of treatment. The development of photosensitivity depends on the total dose of AD; 40 g is the minimal cumulative dose requirement. Under the regimens commonly used, photosensitivity can be expected after 4 months of continuous AD treatment and appears to be unrelated to the skin type. Photosensitivity gradually decreases and returns to normal between 4 and 12 months after the withdrawal of AD. AD-related hyperpigmentation develops after an average of 20 months of continuous AD treatment and a minimal total dose of 160 g AD in about 8% of the patients (mainly of skin type I). Electron microscopic examination of the sun-exposed skin of patients without AD discoloration shows pigment deposits similar to those already described in patients with AD hyperpigmentation in exposed and non-exposed skin. Light and electronmicroscopic examination of sun-exposed skin of both clinically photosensitive and non-photosensitive patients reveals perivascular inflammation even in the absence of a clinical rash. Reduplications of vascular basal laminae occur in sun-exposed skin of both patients with and without UVA photosensitivity but are absent from non-exposed skin. In one patient, followed for 33 months after drug withdrawal, massive AD-induced hyperpigmentation was found to be reversible.

Amiodarone↗
PubMed1989

An unusual combination of phototoxicity and Stevens-Johnson syndrome due to antimalarial therapy.

A 12-year-old boy developed a phototoxic rash with subsequent progression to Stevens-Johnson syndrome due to prophylactic ingestion of antimalarials (chloroquine and sulfadoxine-pyrimethamine; Fansidar). The patient recovered from his skin symptoms after 4 weeks during which he received systemic corticosteroids and antibiotics. This unusual combination of two different patterns of adverse cutaneous drug reactions was most probably caused by the sulfonamide component of Fansidar.

Antimalarials↗
PubMed1988

[Polymorphous photodermatosis--photobiologic diagnosis and therapy].

Polymorphous light eruption is an acquired photodermatosis, whose causal factors have not yet been identified. The diagnosis is based on the clinical picture and on histology. During the symptomless periods, photo-testing is the most important technique to confirm the diagnosis, since there are no specific laboratory parameters. Regarding our own patients, typical lesions could be provoked by UVA in 50%, by UVB in 20% and by both in 30%. The majority of the patients can be protected during the summer season by intermittent preventive photo(chemo)therapy.

Antibodies, Antinuclear↗
PubMed1988

Treatment of vitiligo with khellin and ultraviolet A.

Twenty-eight patients with vitiligo were treated with a new photochemotherapeutic regimen using khellin, a furanochromone, as photosensitizer, together with ultraviolet A (UVA) irradiation. Twenty-five patients received khellin orally and three patients were treated with topical khellin. Treatments were given three times weekly. As opposed to psoralens, khellin did not induce skin phototoxicity with UVA but it induced repigmentation similar to psoralens. The treatment success strongly depended on the number of treatments. More than 70% repigmentation was achieved in 41% of the patients who had received 100 to 200 treatments. This success rate is comparable to the rate obtained with psoralens. Seven patients experienced a mild elevation of liver transaminases within the early treatment phase and their treatments were discontinued. No long-term internal organ or skin toxicity was observed. The major advantage of khellin is that it does not lead to phototoxic skin erythema and thus can be considered safe for home treatment. Because of its photochemistry it may be considered less hazardous than psoralens regarding mutagenicity and carcinogenicity.

Adolescent↗
PubMed1988

Phototherapeutic, photobiologic, and photosensitizing properties of khellin.

Khellin, whose chemical structure closely resembles that of psoralen, is reported to be an efficient drug for treating vitiligo when combined with ultraviolet A irradiation. Photobiological activity on yeast is found to be much lower than that of bifunctional psoralens such as 5-methoxypsoralen. In vitro experiments reveal that khellin is a poor photosensitizer. It behaves as a monofunctional agent with respect to DNA photoaddition. It does not photoinduce cross-links in DNA in vitro or in Chinese hamster cells in vivo. This behavior may explain the low photogenotoxicity in yeast and the lack of phototoxic erythemal response when treating vitiligo with khellin.

Animals↗
PubMed1988

5-Methoxypsoralen (Bergapten) for photochemotherapy. Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation.

In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.

5-Methoxypsoralen↗
PubMed1987

UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo.

Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.

Adult↗
PubMed1987

[Lymphomatoid granulomatosis].

We present two patients with lymphomatoid granulomatosis (LG) which was diagnosed from the histopathology of cutaneous lesions. Combined cytostatic and corticosteroid treatment induced transient, partial remission in one case, but a lethal outcome could not be prevented in either case. Monoclonal-antibody typing of lesional infiltrates indicated that LG is a malignant T-cell lymphoma.

Aged↗
PubMed1986

Specificity of ganglioside binding to rat macrophages.

The binding specificity of rat alveolar macrophages (AM phi) for sheep erythrocytes (E) coated with gangliosides GM1, GM2, GM3, GD1a, GD1b or GT1b was analyzed in a rosette assay by studying the inhibitory effect of gangliosides, various carbohydrates, IgG, C3b-like C3, and fibronectin in this assay. The uptake of gangliosides by E was calculated from radioactivity measurements using 3H-labeled gangliosides. The different gangliosides were taken up by E at 37 degrees C to a similar extent. Uptake of 3H-labeled GM2 correlated linearly to its concn in the incubation medium. Erythrocytes pretreated with the same molar concn of GM2, GD1a, GD1b or GT1b were bound to AM phi to the same degree reaching a maximum of about 90% rosette forming cells. A mean of 17.8% AM phi-bound GM3-coated E. Treatment of E with asialo-GM2 (GA2) or GM1 did not induce significant rosette formation. A dose-dependent inhibition of rosette formation was observed when AM phi were preincubated at 0 degree C with GM2, GM3, GD1a, GD1b or GT1b, but not with GM1 or GA2 Of the tested carbohydrates, sialyl-lactose had a strong inhibitory effect, while lactose was completely ineffective. N-acetyl-neuraminic acid, N-glycolyl-neuraminic acid and N-acetyl-galactosamine were slightly inhibitory. A series of other carbohydrates including highly negatively charged compounds, as well as fibronectin, IgG or C3b-like C3 did not show significant inhibition. Our data indicate the expression of a receptor on rat AM phi recognizing carbohydrates containing sialic acid at or near the non-reducing terminus.

Animals↗
PubMed1986

Polymorphous light eruption: action spectrum and photoprotection.

Polymorphous light eruption is a common seasonal photodermatosis with a typical history and clinical picture. In the interval, when no lesions are present, the diagnosis relies on artificial reproduction of polymorphous light eruption by phototesting. Photochemotherapy (psoralens with ultraviolet A [PUVA]) is currently an effective preventive treatment. One hundred sixty-seven patients with either a history of polymorphous light eruption or manifest disease entered our study. Of 142 patients tested, 49% developed typical lesions of polymorphous light eruption at the test sites. In 56% the action spectrum was found to be in the ultraviolet A range, in 17% in the ultraviolet B range, and in 26% in both ranges. A total of 122 patients received preventive treatment with PUVA. Of these, fifty-one returned for follow-up. Of the patients who were followed up, 64% reported total protection during outdoor activities in the summer, 26% reported partial protection, and 10% were not protected. Failure to improve was unrelated to the action spectrum. The action spectrum and the incidence of positive results on phototests in our patient population differed from those reported by others. It is possible that differences in the test protocols and in the light sources used may account for this discrepancy. There is clearly a need for a standardized test procedure. However, the majority of patients benefit from PUVA pretreatment regardless of their action spectrum.

Adolescent↗
PubMed1986

Nonmelanoma skin tumors in long-term photochemotherapy treatment of psoriasis. An 8-year follow-up study.

Two hundred ninety-seven long-term photochemotherapy (PUVA)-treated patients from an original cohort of 418 subjects reported in 1980 were reevaluated in a second follow-up in order to determine the risk of tumor development under long-term PUVA. Within an observation period of up to 8 years (mean, 63.1 months) six patients with squamous cell carcinomas and three with basal cell carcinomas were observed. Eight of the nine tumor patients had been exposed to potential carcinogens such as arsenic and/or ionizing radiation prior to PUVA treatment. Five with squamous cell carcinomas were skin type I or II; in four of the six patients with squamous cell carcinomas the tumors were located on unexposed skin areas. The mean cumulative ultraviolet A (UVA) dose in three of the six squamous cell carcinoma patients was three times as high as that in the group of nontumor patients. The other three squamous cell carcinoma patients had lower mean doses than nontumor patients, as did the three patients with basal cell carcinomas. Although the cumulative UVA dose may eventually turn out to be relevant for PUVA carcinogenesis, our present data do not sufficiently substantiate a correlation between cumulative UVA dose and squamous cell carcinoma formation in PUVA-treated patients. This report confirms that previous exposure to carcinogens appears to be the most important factor for nonmelanoma skin tumor formation in long-term PUVA patients.

Adult↗