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Biomedical subjects

M Bjellerup

Publications and source records attributed to M Bjellerup.

33 records · Page 2Linked to original sources

Systemic drug photosensitivity.

Photosensitivity as a side effect in treatment with systemic drugs occurs both as a phototoxic, non-immunologic phenomenon and as a photoallergic, immune-dependent reaction. The former principle is the more common one, and is seen with a number of non-related, widely used drug groups such as the tetracyclines, the phenothiazines, nonsteroidal antiinflammatory drugs, nalidixic acid, amiodarone and griseofulvin. For some of these drugs, for quinidine/quinine, and for the sulfonamides and related drugs, the reactions are probably also photoallergic. The majority of photosensitizing drugs have an action spectrum within UVA. Experimental studies have revealed that photoproducts and metabolites in some instances make important contributions to the biological photoreaction. For several of these drug groups, progress is presently underway in elucidating their mechanisms of action, as well as the relationship between chemical structure and in vivo photoactivity.

Amiodarone↗

Photohemolytic potency of tetracyclines.

Hemolysis induced by long-wave ultraviolet radiation (UVA) and 8 different commercial tetracycline derivatives was studied in a model using human red blood cells. Demethylchlortetracycline and doxycycline were shown to have pronounced hemolytic properties causing 88% and 85% hemolysis, respectively, at a concentration of 50 micrograms/ml and 72 J/cm2 of UVA. Tetracycline, oxytetracycline, and chlortetracycline caused maximally 18% hemolysis at 200 micrograms/ml and lymecycline only 7% at 100 micrograms/ml. Methacycline showed intermediate hemolytic effect of 36% at 200 micrograms/ml. Minocycline had no hemolytic effect whatsoever. These experimental data correlate very well with clinical reports and comparative phototoxicity trials in humans. Photohemolysis may thus be of value for predicting tetracycline phototoxicity.

Hemolysis↗

Influence of tetracycline phototoxicity on the growth of cultured human fibroblasts.

The phototoxic effect of 8 different commercial tetracycline derivatives with long-wave ultraviolet radiation (UVA) on the growth pattern of normal human skin fibroblasts in culture was studied. Chlortetracycline and doxycycline both at a concentration of 50 micrograms/ml and 1.9 J/cm2 of UVA resulted in total cell death with no recovery during a 14-day observation period. Demethylchlortetracycline also showed strong photosensitizing properties with an arrested cell division for 7 days followed by a recurrence of cell growth. The other tetracyclines tested under identical conditions had only weak or no phototoxic influence on cell growth. These experimental data correlate very well with clinical reports and comparative phototoxicity trials in humans. This experimental method may thus be of value for predicting tetracycline phototoxicity in humans.

Adolescent↗

Studies on photohemolysis with special reference to demethylchlortetracycline.

Hemolysis induced by ultraviolet radiation as well as demethylchloretetracycline (DMCT) phototoxicity have been investigated in a model using human red blood cells. Total hemolysis for UV-B and UV-C was obtained with 8.3 and 1.9 J/cm2 respectively. DMCT was shown to have pronounced hemolytic properties causing 88% hemolysis at 50 micrograms/ml and 72 J/cm2 of UV-A. No increased hemolysis rate was seen in combination with UV-B. Several factors influencing the results were studied such as incubation time, UV-A dose, drug concentration and different methods for hemoglobin detection. Photohemolysis is an accurate tool for demonstrating DMCT phototoxicity.

Chlorpromazine↗

Experimental studies on the mechanism of benoxaprofen photoreactions.

Benoxaprofen (BP), a non-steroidal antiphlogistic drug causing skin and nail photoreactions, has been evaluated for photoactivity using three experimental techniques. In vivo in the mouse, BP was phototoxic in doses of 25 mg/kg in combination with UV-A 54J. The phototoxic potency could be confirmed in vitro with the Candida albicans test. In vitro, using photohemolysis, BP showed a dose-dependent activity causing 40% hemolysis at a concentration of about 25 micrograms/ml with UV-A. Also, small UV-B doses caused red cell lysis with a moderate BP concentration. Pre-irradiation experiments showed that UV-A, but not UV-B, photoproducts could account for some of the activity. The action spectrum of BP photoactivity lies mainly in the UV-A, but may also extend into UV-B. Compared with chlorpromazine in vivo and in vitro, and with doxycycline in vivo, BP showed intermediate phototoxic activity.

Animals↗

Dose-response relations in phototoxicity due to 8-methoxypsoralen and UV-A in man.

Serum levels and skin photosensitivity following different oral doses of 8-methoxypsoralen (8-MOP) were studied in 8 healthy volunteers. Two hours after ingestion of drug, serum levels of 8-MOP determined by high pressure liquid chromatography correlated well with oral dose. Serum concentrations after 8-MOP doses of 0.3, 0.6 and 0.9 mg/kg bodyweight were 25.9 (+/- 7.2), 148.9 (+/- 24.4) and 311.4 (+/- 55.6) ng/ml (mean and SEM) respectively. The minimal phototoxic dose (MPD) of UVA 2 hr after ingesting 8-MOP was determined in 6 volunteers for each of the 3 before-mentioned 8-MOP doses. The UV-A doses correlated inversely with the serum level for each individual (r = 0.92 +/- 0.02 SEM). For higher 8-MOP doses the numerical product of UV-A dose and 8-MOP serum concentration in each individual tended to be constant, indicating a reciprocal relationship between 8-MOP and UV-A doses in this interval. This did not hold true for the lowest 8-MOP-dose. These data confirm the relevance of using 8-MOP blood level determinations in monitoring psoralen-UV-A phototoxicity.

Adult↗

Photoaugmentation in drug phototoxicity.

The phototoxic reaction to chlorpromazine and other drugs is provoked by long-wave ultraviolet light (UVA). It was shown by the in vivo mouse tail technique that the reaction is enhanced by medium-wave ultraviolet light (UVB), thus demonstrating the importance of photoaugmentation in this process.

Animals↗

Antinuclear antibodies during Puva therapy.

During PUVA therapy 7 patients out of 34 with severe psoriasis developed circulating antinuclear antibodies (ANA) (21%). Before treatment only 3 patients of 50 (6%) considered for PUVA had detectable ANA. The ANA titres were usually low. Antibodies against native DNA as studied with the Crithidia luciliae test, were not found, and blood and urinary screening for collagenosis was negative. All 7 patients responded well to the PUVA treatment. The significance of these findings remains to be determined.

Adult↗

Liver injury following administration of 8-methoxypsoralen during PUVA therapy.

A case of liver injury caused by 8-methoxypsoralen given orally during PUVA therapy is presented. The reaction, manifested by elevated serum alanine-aminotransferase and serum aspartate-aminotransferase, was provoked on three consecutive occasions, on the last one with 8-MOP only. The liver injury seems to be of the hepatocellular and nonpredictable type.

Alanine Transaminase↗

Analysis of therapy-resistant venous leg ulcers. Can triple-layer treatment initiate healing?

Chronic leg ulcers represent a major health-care problem with considerable socioeconomic impact. Patients with seemingly therapy-resistant leg ulcers are common to all clinics. The purpose of the present study was to (1) examine a group of patients with nonhealing venous leg ulcers treated with a double-layer bandage and (2) evaluate whether the addition of an interactive hydrocolloid wound dressing could initiate healing in these patients. Twenty-two patients with ulcers caused by venous insufficiency were included. The patients had a mean ulcer duration of 27.6 years. Duration of the present ulcer was at least 1 year (mean >/= 4.1 years). Twenty of the 22 patients showed massive lipodermatosclerosis. Before inclusion, all patients had used double-layer bandage consisting of a zinc-impregnated bandage or stocking and a self-adhesive compression bandage for 1 year or longer without improvement. The new regimen was a triple-layer treatment with the hydrocolloid water applied over the ulcer and the traditional double-layer bandage unchanged. Three patients were dropped from the study. Nineteen patients were followed until healing or for 10 months. Nine of the 19 patients who completed the study healed. Ulcer area was reduced by 70% or greater in 7 patients and by 30% to 40% in two patients. One ulcer did not respond to the treatment and worsened slightly. The results of this study were encouraging and indicate that the triple-layer treatment with the hydrocolloid dressing applied to the ulcer should be evaluated in a randomized, controlled study in patients with less pessimistic prognoses.

Journal Article↗

Excision of lipodermatosclerotic tissue: an effective treatment for non-healing venous ulcers.

In longstanding venous ulcers, the development of lipodermatosclerosis of the skin surrounding the ulcer is common. According to our clinical experience lipodermatosclerosis impairs the opportunities for the ulcer to heal. In this combined retrospective and prospective study the lipodermatosclerotic skin area was excised in 7 non-healing venous ulcers and then covered with split skin graft. All 7 legs had previously been treated with superficial venous surgery. Laser Doppler scanning of the ulcer area was performed pre- and postoperatively. Five of the 7 ulcers healed within 4 months and 1 healed within 9 months. Laser Doppler scanning showed increased blood flow in the lipodermatosclerotic skin area, which was decreased after the operation. This study indicates that excision of the lipodermatosclerotic skin area followed by split skin grafting can accomplish healing in non-healing venous leg ulcers that have failed to respond to previous superficial venous surgery.

Adipose Tissue↗

Perianal abscess and sinuses caused by granuloma inguinale. Case report.

An atypical case of the venereal disease granuloma inguinale, which is very rare in Scandinavia, is reported. The patient presented with recurrent perianal abscess and sinuses, and the diagnosis was not made until histologic examination of an extirpated subcutaneous nodule showed cells containing the pathognomonic Donovan bodies.

Abscess↗