Biomedical subjects
Publications and source records attributed to L Hellgren.
Small bipsies of the skin were taken from patients with papulo-cutaneous mastocytosis. The mast cell tumours were then degranulated with compound 48/80 (250 mug/ml in saline), and with a Sorption microcalorimeter, relatively strong exothermic reactions were measured, whereas normal skin showed only 1/10th the intensity. Disodium chromoglicate (1%) had no inhibitory effect on this thermal reaction.
Necrotic materials most frequently found in leg ulcers, including crusts with fibrinogen, pus and blood clots, were exposed to solutions of streptokinase-streptodornase and stabilized crystalline trypsin respectively. The investigations were performed at the temperatures of 26 degrees and 33 degrees C, representing the extreme values of the temperature range found in leg ulcers (arteriosclerotic ulcers, stasis ulcers) and at the pH corresponding to that of the enzyme preparations in wet dressings. Streptokinase-streptodornase demonstrated in vitro a more potent proteolytic activity than crystalline trypsin on necroses, crusts of fibrinoid and purulent exudate, which were more rapidly and thoroughly broken up. Both enzyme preparations were, however, equally effective on three-day-old blood clots.
In order to visualise the morphological changes of Epidermophyton floccosum associated with exposure to perdeuteriated n-hendecanoic acid, the architecture of the dermatophyte was investigated by means of interference contrast and scanning electron microscopy. The morphology of mycelia grown on substrate containing perdeuteriated n-hendecanoic acid, or the unlabelled analogue, was compared. The perdeuteriated n-hendecanoic acid produced a characteristic undulant effect of the hyphae. The characteristic wave-like appearance of the mycelia looked similar to the curling effect occuring after treatment of dermatophytes with griseofulvin, but was not so pronounced. Perdeuteriated n-hendecanoic acid, unlike the unlabelled analogue, also seems to cause a reduction of the number of chlamydospores perforations of the macroconidia. The changes in the morphological structure of Epidermophyton floccosum exposed to pereuteriated n-hendecanoic acid have been investigated. Morphological examination of mycelia exposed to this substance by interference contrast microscopy demonstrated a picture of defect hyphae and macroconidia. By the aid of scanning electron microscopy we have attempted to obtain a better visualization of these changes at ultrastructural level.
Investigations on the antimycotic properties of perdeuteriated fatty acids were carried out on Microsporum cains infections in vivo. The study was performed on experimental microsporie in guinea pigs using four different methods, all based on the ability of M. canis to cause alopecia. Perdeuteriated n-hendecanoic acid showed in vivo a statistically significant enhanced antimycotic effect compared to its unlabelled analogue. This is in accordance with our previous observations in vitro conditions. The remaining perdeuteriated fatty acids (C12--C18) showed no statistically significant growth retarding effect on M. canis infections in guinea pigs when compared with their unlabelled analogues. The present study attempts to ascertain if some perdeuteriated fatty acids have any antifungal activity in vivo conditions. Our previous papers (3,4) concerning the evaluation of the antifungal activity of some perdeuteriated fatty acids on dermatophytes in vitro, demonstrated that the perdeuteriation of n-hendecanoic acid, lead to a pronounced antimycotic effect on common dermatophytes as e.g. E. floccosum, T. rubrum, M. canis and T. mentagrophytes. As our previous results indicate a decreasing of fungistasis with an increasing carbon-chain length of the perdeuteriated fatty acids, we have attempted to verify this observation in vivo conditions. A special interest was, of course, focused on the most promising compound, the perdeuteriated n-hendecanoic acid.
Crude trichophytin was fractionated to find out if its lipid fraction could cause inflammatory delayed allergic skin reactions in dermatophyte-sensitized guinea pigs. The following fractions were obtained: polysaccharide-peptide, total lipids, total lipids without free fatty acids and free fatty acids. The crude trichophytin and polysaccharide-peptide fraction gave rise to strong and equal allergic delayed skin reactions after 24 h. The total lipids gave statistically significant weaker, but clearly positive reactions, and of the same degree as the free fatty acid fraction. The total lipids without free fatty acids did not produce reactions in the sensitized animals, indicating that free fatty acids are responsible for the allergic skin reactions. In some cases the free fatty acids showed comparatively intense reactions. It can be concluded that free fatty acids are antigenic substances that are, sometimes, involved in the allergic delayed skin reactions in dermatophytosis.
The predominant fatty acids (C10-C18) of dermatophytes were investigated by the Landsteiner-Draize test to establish their allergenicity. It was demonstrated that fatty acids can give rise to sensitization of delayed type in guinea pigs. The middle-chain fatty acids (C10-C12) showed a high allergenicity compared to the (C13-C18) acids with moderate to weak contact sensitizing properties. The fatty acids may act as contact sensitizers and, at least sometimes, be responsible for the skin lesions in dermatophytosis.
By spark source mass spectrography it is possible to trace very low concentrations of substances such as chromium, cobalt, and nickel in ethanol extracts of the skin. Chromium could be detected in abnormally high concentrations 3 weeks after one application, while nickel and cobalt reached background levels after 2 to 3 weeks. Touching a door handle containing chromium leads to a significant rise in the chromium content of the skin. Increased chromium content of the skin was evident in one case of wristwatch eczema as well.
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A clinical evaluation was carried out in 19 patients with lichen ruber planus to assess the effectiveness of 0.05% betamethasone-17,21-dipropionate ointment in the treatment of patients whose lesions had developed resistance to prolonged treatment with 0.1% betamethasone-17-valerate ointment. The new steroid ointment was substituted for the previous preparation and applied at the same frequency, once or twice daily, for 2 to 3 weeks. The results at the end of the betamethasone-17,21-dipropionate period were classified as better in 14 (73.7%) and equal in the remaining 5 patients.
Distributed on 66 occupational groups (and 170 individual occupations) the prevalence of lichen ruber planus within the groups was determined by examining nearly every person in the total populations of 39,418 persons in five different areas in Sweden. The prevalence of l.r.p. in the total population was 0.3 per cent for males and 0.1 per cent for females. When l.r.p. prevalences were compared between different occupational groups, disturbing influences from age differences between the groups were eliminated by the standard population method. The indices calculated by aid of computer were used for direct ranking of the occupational groups from those with the highest to those with the lowest prevalences. In 33 of the 66 occupational groups (and in 129 of 170 individual occupations) no l.r.p. was found. In 24 male and 6 female occupational groups an overaverage high prevalence of l.r.p. was found. In two occupational branches, i.e. agriculture and forestry work (male agricultural workers, farmers, gardeners, garden workers and forest workers) and engineering and building metal work (steel-workers, plate-workers, machine and engine repairers, machine and engine mechanics, engineering workers, plumbers, metal workers) an overaverage high prevalence of l.r.p. was found in nearly all occupational groups. The results indicate that l.r.p. is more prevalent in occupational groups, in which the work dirties the skin (with i.e. soil, oil, cement dust), while in occupational groups with "clean work" the disease was less prevalent. However, there were exceptions. 67.7% of the males, 55.5% of the females had their debute lesions on the lower legs; in 21% of the males and 22.2% of the females the l.r.p. lesions debuted on the wrists. These are areas liable to exposure for different chemical substances and trauma.
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Three patients with chronic discoid psoriasis are described as having a generalized pustular eruption provoked by the topical use of betamethasone-dipropionate ointment (0.05%) over extensive skin areas for two or three weeks. All the lesions were nearly healed when the rash erupted. It is suggested that the potent topical steroid was absorbed through the damaged psoriatic skin, resulting in a systemic effect and a generalized pustular psoriasis (GPP). It was estimated that the patients absorbed at least 1.5 mg betamethasone per day during the application period.(i.e. 3 tablets of CelestonaR 0.5 mg). Just as steroids systemically are contraindicated in chronic discoid psoriasis by the risk of GPP, potent topical steroids must be avoided over large psoriatic skin areas.
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Thin-layer chromatography was used to find out if there were any quantitative differences in fatty acid content in pus from the palmar pustules in ten patients with psoriasis pustulosa palmo-plantaris (PPP) before and after long-term tetracycline therapy. No significant differences were found, indicating that it was not possible to correlate the good therapeutic effect of antibiotics reported in PPP with a decrease in the fatty acid content of pus from the pustles. However, the series was small and investigations are now in progress to establish whether small differences of significance can be demonstrated in a larger series. By combined gas chromatography and mass spectrometry the fatty acids of pus in patients with psoriasis pustulosa palmo-plantaris were analysed. Stearic and palmitic acids were found to be predominant.
Infrared spectroscopy was used to trace active substances and ointment vehicles applied on the skin. Vaseline and lanoline could be traced after 8 hrs but not olive oil. From the active substances, ethyl-4-amino-benzoate (5 per cent), clioquinol (5 per cent), parabenes (15 per cent), 5,7-dichlor-8-hydroxy-2-methyl-chinolin (5 per cent), balsam of Peru (25 per cent) and pyroleum pini (12 per cent) could be traced 1 hr after application but had disappeared after 8 hrs. Ethylenediamine (1 per cent), chlorcresol (1 per cent), pyroleum lithantracis (5 per cent), were not traceable after 1 hr, and curiously neither neomycine sulphate in spite of its high concentration (20 per cent). The reaction of the skin surface lipids, after application of different substances, was deduced from the spectra. Clioquinol and pyroleum lithantracis seem to give rise to hydrolysis of the triglycerides, the free fatty acids being clearly identifiable. It is felt that infrared spectroscopy can be used as an effective method to trace different substances such as potent allergens on healthy or diseased skin.
Using the Guinea Pig Maximization Test, the sensitization rate of a perfume was shown to be 10 per cent, which means a mild allergenicity rate. A usage sensitization trial was performed with the same perfume included in a soap, on 300 persons for 2-3 months. Seventy-five of these, all house-wives, were randomly selected and tested epicutaneously, after the trial. One woman reacted allergically towards the perfume. This means a sensitization rate of 1.3 per cent, which is a maximum value, as she could, theoretically, have been sensitized before.
In a double-blind trial over a 2-week period in 34 patients with psoriases vulgaris, clobetasol propionate cream was shown to be more effective than betamethasone valerate cream. In a further 16 patients whose psoriasis had not responded to betamethasone valerate ointment, treatment with clobetasol propionate ointment was substituted. Fourteen of the 16 patients experienced a rapid improvement of their lesions.