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Biomedical subjects

P Bjerring

Publications and source records attributed to P Bjerring.

At least 145 records · Page 8Linked to original sources

Topical treatment of psoriatic skin with methotrexate cream: a clinical, pharmacokinetic, and histological study.

Five patients were treated with either 0.25% methotrexate cream or placebo in a double blind trial. The evaluation showed no clinical or histological effect although the drug was absorbed from the skin. Methotrexate (MTX) accumulated in locally treated psoriasis plaques as well as in untreated plaques. The psoriatic skin concentrations were increased by a factor of 119 and 4, respectively. This observation is discussed in relation to the possible role of action of methotrexate in psoriasis. We suggest that methotrexate inhibits the chemotaxis of neutrophil leukocytes systemically and not primarily in the skin, thereby preventing development of the early stages in the psoriatic lesions.

Administration, Topical↗

Synthesis, tissue distribution and cytostatic properties of two new daunorubicin derivatives of 2-thiouracil containing a guanidine bridge.

In further attempts to utilize the affinity of 2-thiouracil for melanin-producing tissues in the design of drugs active against malignant melanomas, guanidine-bridged adducts of the anthraquinone drug daunorubicin (1a) with 2-thiouracil were prepared (Scheme 3). The expected adduct (4), and a by-product in its preparation (5) (Scheme 3), were inactive against murine melanoma, in vivo, and did not show affinity for melanin-producing tissues. They were efficient DNA intercalating agents, but were much less cytostatic than daunorubicin against Cloudman melanoma, and were inactive, in vitro, against human cervical carcinoma MS 751. The coupling chemistry employed may have application in current attempts to effect binding of drugs to high molecular weight targeting antigens.

Animals↗

Selenium inhibits UV-light-induced skin carcinogenesis in hairless mice.

Female hairless inbred hr/hr mice were exposed to UV-B irradiation from Philips TL 40W/12 fluorescent tubes. Fractionated irradiation, given as single daily doses 5 days a week, was gradually increased from 0.04 to 0.4 J/cm2 over 2 weeks. Irradiation at 0.4 J/cm2 was continued for 20 weeks. Selenium supplementation given as sodium selenite in the drinking water at 2, 4 and 8 mg/l began 3 weeks before UV-irradiation and continued thereafter. Development of skin tumors was followed by weekly examinations. Statistical analyses revealed significant dose-dependent selenium-mediated protection against UV-light-induced skin cancer. Leukemia developed in 5 of 150 UV-irradiated mice as opposed to none in a group of 60 unirradiated mice.

Animals↗

Psoralenamines. 3. Synthesis, pharmacological behavior, and DNA binding of 5-(aminomethyl)-8-methoxy-, 5-[[(3-aminopropyl)oxy]methyl]-, and 8-[(3-aminopropyl)oxy]psoralen derivatives.

A series of derivatives of 5-(aminomethyl)-8-methoxypsoralens, 8-[(3-aminopropyl)oxy]psoralens, and 5-[[[3-(tri-methylammonio)propyl]methyl]-8-methoxypsoralen has been synthesized and their potential as PUVA reagents examined. While the DNA association constants of selected psoralens were found to be 10(5)-10(6)L mol-1, corresponding to efficient binding, flow linear dichroism studies indicated that only the 8-substituted psoralens bind to DNA by intercalation. Furthermore, the ability to photoinduce interstrand cross-links in calf thymus DNA, in vitro, was as efficient as that of 8-methoxypsoralen for the 8-substituted psoralens, which were up to 25 times as efficient as the 5-substituted psoralens. Four of the psoralens studied were radiolabeled and used to study photobinding to DNA. Analogously to the cross-binding results, the 8-substituted psoralens were more efficiently photobound than the 5-substituted, while only slight differences were found in the photobinding-cross-linking ratio. The photoreactivity of the aminopsoralens toward cyclohexene and 2'-deoxythymidine was enhanced compared to that of 8-methoxypsoralen, the effect being most pronounced when the amino group is close to the furocoumarin ring system. Most of the new compounds were less photocytotoxic than 8-methoxypsoralen to NHIK 3025 cells, in vitro, and they caused less light-induced DNA interstrand cross-linking, in situ, in these cells. A clear correlation between the photocytotoxicity and the DNA cross-linking ability of the psoralens was observed. Several of the derivatives showed more pronounced effects in the light-dependent skin thickening (inflammatory) test on mice than 8-methoxypsoralen. No correlation between DNA cross-linking capacity, in vitro, and skin phototoxicity was found for this series of psoralens.

Animals↗

Skin elasticity measured by dynamic admittance. A new technique for mechanical measurements in patients with scleroderma.

A new method is presented for determining overall mechanical properties of the skin. The technique is called dynamic admittance measurement. By computerized calculations of mechanical resonance measurements, information is obtained on the elastic modulus representing the type and amount of collagen in the skin, the quality factor describing the mechanical quality (effectiveness) of the collagen, and the mechanical resistance of the viscous, non-elastic component of the skin. The method is suitable for measuring mechanical properties of small skin areas, e.g. distally on the fingers in acrosclerotic lesions of scleroderma. Highly reproducible, standardized results are obtained. In generalized scleroderma, the elastic modulus of the cutaneous network of collagen and elastin is increased, not only in clinically affected skin, but also in clinically unaffected areas, whereas the mechanical quality factor and the viscous resistance (mechanical impedance) was unaltered in scleroderma compared with normal controls. The dynamic admittance method for determining the mechanical properties of the skin in vivo may be of importance for accurate monitoring of disease status and for assessing the effect of therapy in diseases, where alterations in the mechanical properties of the skin are of significance.

Adolescent↗

Histologic changes in the liver during etretinate treatment.

Histologic changes in the liver were evaluated in thirty-two patients with different dyskeratotic dermatoses treated with etretinate (Tigason) during an average of 24.9 months. Fatty infiltration, nuclear variability, periportal inflammation, focal necrosis, fibrosis, and cholestasis were estimated. The usual dose was 50-75 mg/day, with reduction according to efficacy and side effects. No statistically significant differences were found between a control group of thirty-five liver biopsies from psoriasis patients who had not received systemic therapy and biopsies from the patients treated with etretinate. Among the thirty-two etretinate-treated patients, six had two serial biopsies, and eight had pretreatment biopsies. No significant changes appeared during therapy.

Adolescent↗

Susceptibility to carcinogenic effect of irradiation. Relationship to age at time of exposure.

Age at time of exposure is an important host factor influencing the subsequent cancer risk. Before completion of organogenesis, the fetus may be rather resistant, but thereafter the growing tissues of children are more susceptible than those of young adults. At greater age of adults at the time of exposure there is an increase in the subsequent absolute number of 'excess' cancer cases, but the relative risk (excess in relation to expectation) is rather constant for a given kind of radiation exposure as judged from the presently rather small number of investigations.

Adult↗

Eosinophilic granuloma associated with a 16q22 chromosomal defect of cutaneous T lymphocytes.

A 61-year-old woman presented with circumscribed eczematous eruptions with maceration, erosions and patchy infiltration in the perineum and inframammary regions. A diagnosis of eosinophilic granuloma (cutaneous histiocytosis X) was established. T lymphocytes from a skin biopsy were grown in vitro for three weeks after which chromosomal studies revealed a break or gap at chromosome 16q22 in 15% of the lymphocytes. The addition of alpha-interferon increased the percentage of affected cells to 28%. T lymphocytes from the patient's blood did not show the defect. The biological significance of the chromosomal defect is uncertain. It has been described before in healthy persons, malignant lymphoma, cold urticaria and IgA deficiency, and mental retardation. It has not been seen in patients with eosinophilic granuloma.

Biopsy↗

Oral selenium inhibits skin reactions to UV light in hairless mice.

In different experimental systems oral selenium has a pronounced anti-carcinogenic effect. This includes both spontaneous and chemically-induced cancers (1, 2, 3, 6, 7, 8). Our primary objective was to study the effect of selenium on the carcinogenic potential of UV light in hairless mice. Fairly early in these experiments, however, it became obvious that the selenium-supplemented mice were considerably more resistant to the acute and sub-acute effects of UV light than were the unsupplemented animals. This was found for the inflammatory reaction as well as for the development of pigmentation. As far as we know, this effect of selenium has not previously been described.

Animals↗

Results of lymphography in early mycosis fungoides.

Lymphography was performed in 28 patients with mycosis fungoides. In 22 of the patients, the investigation took place prior to 2 months after the diagnosis was established, and in 7 of these lymphography was made before the histological verification of mycosis fungoides was possible. Five patients with widespread, persistent and severe atopic dermatitis served as controls. Eighteen patients with mycosis fungoides (64%) had abnormal lymphograms, while all 5 controls had normal lymphograms. Abnormal findings were diagnosed in 12 of 22 patients at the earliest time possible during the course of their disease and even found in 5 of 7 patients who only had premycotic lesions at the time of investigation. These results may have some bearing on therapy, suggesting that systemic treatment could possibly be introduced at a far earlier disease stage than is the custom at present.

Dermatitis, Atopic↗

E-rosette formation of lymphocytes from patients with atopic dermatitis.

The total number of circulating T lymphocytes in 47 patients with atopic dermatitis was a significantly lower than in 98 healthy persons. However, when the T lymphocytes were investigated for their affinity to sheep erythrocytes (E-rosette formation), no difference was found between patients and healthy persons, when using several different techniques varying in length of incubation of sheep erythrocytes and lymphocytes, presence of fetal calf serum, glassware, media, increased mechanical force at resuspension, and different observers. Our findings are discussed with reference to earlier publications of a reduced percentage of E-rosette forming lymphocytes in patients with atopic dermatitis.

Adolescent↗

Treatment of Kaposi's varicelliform eruption wit adenine arabinoside (Vira-A) and transfer factor.

Kaposi's varicelliform eruptions, or Eczema herpeticum, are the result of a herpes virus infection. This paper reports on a patient who was treated with parenteral infusion of a new anti-viral drug, adenine arabinoside (Vira-A), and transfer factor in an attempt to halt the spread and alleviate the severity of the disease. It is our opinion that adenine arabinoside can have a beneficial effect on the course of the disease.

Adult↗

Methotrexate in psoriasis with and without leucovorin: effect of different dosage schedules on acute liver toxicity.

Studies on thirty-six psoriatics revealed no differences in acute liver toxicity of four different intermittent dosage schedules of methotrexate with or without addition of leucovorin, as judged by daily determinations of SGOT for one week. Three patients with psoriatic erythroderma receiving high-dosage methotrexate (100 mg i.v.) with leucovorin rescue responded extremely well to treatment and did not distinguish themselves from the other patients with regard to acute liver toxicity.

Administration, Oral↗

Effect of EMLA cream on skin thickness and subcutaneous venous diameter. A randomized, placebo-controlled study in children.

EMLA cream, which is used to provide analgesia prior to venepuncture, induces a skin-blanching reaction. This reaction may be caused by both skin hydration and vasoconstriction. Twenty healthy children with veins suitable for venepuncture on the dorsa of the hands or at the antecubital fossae had applied either EMLA cream or placebo cream under occlusion for 60-70 min in a randomized, double-blind, cross-over study. An ultrasound examination of the skin was conducted. The mean percentage change in vein diameter after removal of EMLA cream was not significant whereas, 15 min after EMLA cream removal, the decrease in the initial vein diameter (13.5%) was significant (p<0.01). The mean percent increase in skin thickness after the removal of EMLA cream was also significant (19.3%; p=0.01). The changes in vein diameter and skin thickness due to the application of EMLA cream do not seem to be of clinical importance to vein cannulation.

Anesthetics, Local↗