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Biomedical subjects

O Hägermark

Publications and source records attributed to O Hägermark.

At least 37 records · Page 2Linked to original sources

Pruritus in patients on maintenance hemodialysis.

Twenty-nine patients undergoing maintenance hemodialysis were examined for dermatologic symptoms. Nineteen patients (66%) complained of pruritus, which was classified as mild (34%), moderate (24%), and severe (8%). Patients with pruritus did not differ from those without pruritus regarding serum concentrations of creatinine, urea, calcium, alkaline phosphatase or aluminum, nor was there any difference in duration of hemodialysis, age or sex. In pruritic patients serum concentrations of parathyroid hormone were significantly higher when determined with a mid-region radioimmunoassay technique (p less than 0.01) and higher, although not significantly, when the intact parathyroid hormone molecule was measured. Serum concentrations of phosphate were significantly lower in patients with pruritus (p less than 0.05).

Adult↗

Evaluation of a new method of assessing pruritus and antipruritic drugs.

A new method (Pain-Track) for recording subjective symptoms was evaluated for its capacity to quantify clinical itch. The Pain-Track system includes portable data loggers carried by the patients, a personal computer with a software package for storage and analysis of the data and a terminal unit to connect the loggers and computer. Every 60 min a signal from the logger commands the patient to mark his presence and rate the itch intensity. During night time the hourly buzz can be turned off but the intensity rate can be adjusted whenever wanted. The antipruritic effect of betamethasone dipropionate and its cream base was studied according to a double-blind, crossover protocol in 30 adult outpatients with atopic dermatitis, 26 of whom completed the study. Analysis with parametric and nonparametric methods showed that the itch intensity was significantly lower during active treatment than with placebo. Onset of the antipruritic action was rapid. Examination of the 'itch profile' revealed that atopics have more intense itch both in the mornings and evenings than during the day. It is concluded that by using a drug with known antipruritic effect we have shown that Pain-Track is a useful tool for assessing clinical pruritus and the antipruritic effects of drugs. The main advantages are possibilities for frequent recordings, surveillance of compliance improving authenticity, and storage and analysis of a large amount of data.

Adult↗

The sensitivity of uremic and normal human skin to histamine.

Cutaneous reactions induced by intradermal histamine injection were studied in uremic patients with and without pruritus who were undergoing maintenance hemodialysis and also in healthy subjects. Flare reactions were significantly smaller in both groups of patients than in controls. However, the itch responses following histamine injection were greater in patients with pruritus than in non-pruritic patients and healthy subjects, indicating an augmented sensitivity to pruritogens in these patients. The development of histamine tachyphylaxis was demonstrated in healthy human skin. After repeated histamine injections at intervals of 90 min, both itch and flare responses decreased rapidly. A similar decline in histamine reactivity occurred when the interval between injections was extended to 24 h. The phenomenon of histamine tolerance was confirmed in 2 uremic patients.

Adult↗

Inhibition of complement dependent experimental inflammation in human skin by different heparin fractions.

The anticoagulant activity of heparin is dependent on its affinity for antithrombin III (AT III) and on its molecular weight. In contrast, heparin fractions differing in these respects are equally effective inhibitors of the human complement system in vitro. In this study we designed and evaluated a model to investigate the effects of different heparin fractions on a complement dependent inflammation. Locally administered heparin, in a dose-dependent manner, inhibited the flare, itch and wheal responses induced by intradermal injection of heat-aggregated human IgG (HAGG). These reactions were also inhibited by the antihistamine mepyramine, favouring the view that HAGG activates complement and that the observed inflammatory response is mediated by anaphylatoxin liberation of histamine. Similar cutaneous reactions induced by trypsin, which can generate C3a and C5a by proteolysis of C3 and C5, the histamine liberator compound 48/80 or histamine were inhibited by mepyramine but not by heparin. Thus it is strongly suggested that heparin inhibits the HAGG induced reactions by modulating the early pre-C3 steps of complement activation. On a weight basis heparin fractions differing in AT III-affinity or in average molecular weight (5,000 and 16,000 D) were equally potent modulators of the HAGG-induced inflammation. We conclude that heparin can inhibit an apparently complement-dependent inflammation irrespective of its AT III-affinity or of its size, and suggest that a heparin with low anticoagulant activity could be of value as a modulator of inflammation and should be useful in investigating the consequences of complement inhibition in inflammation.

Animals↗

Peripheral antihistamine and central sedative effects of three H1-receptor antagonists.

The effects of single oral doses of three antihistamine compounds on histamine-induced itch and flare reactions were studied in 24 healthy volunteers by a double-blind balanced design. Central sedative effects were concurrently analyzed using a set of computerized neuropsychological tests and analogue ratings. Hydroxyzine 20 mg had a more pronounced inhibitory effect on the cutaneous response than 3 mg clemastine or 3 mg azatadine. Clemastine tended to cause more sedation than the other two drugs. A compound score, reflecting the balance between peripheral and CNS effects, showed hydroxyzine to have relatively more peripheral antihistamine effect and less sedative effect than the other two drugs. The independence of peripheral and CNS antihistamine effects was also suggested by correlation analysis. Subjects displayed individual sensitivity to the peripheral antihistamine effect of the three drugs; a marked antihistamine effect of one drug predicted a marked effect of the other two drugs. This was not the case for CNS sedation. The independence of peripheral and CNS effects should encourage development of new and more specific antihistamine compounds.

Adult↗

Separate effects of topical indomethacin on the itch response and on the flare reaction induced by histamine in human skin.

The effects of topical indomethacin on histamine responses and histamine release were studied in 15 healthy volunteers. Three hours before testing, the indomethacin solution was applied under occlusion on one arm and the corresponding vehicle on the other. Solutions of histamine and the histamine releasing compound 48/80 were injected intradermally in both arms. Indomethacin treatment inhibited the flare reactions induced by histamine and compound 48/80 to about 50%, whereas no influence was seen on the itch responses. Our results indicate that indomethacin has no effect on the release of histamine, but it selectively suppresses the histamine-induced flare reaction leaving the itch duration unaffected.

Administration, Topical↗

Experimental pruritus evoked by platelet activating factor (PAF-acether) in human skin.

Cutaneous pruritic effects of synthetic platelet activating factor (PAF-acether) and, in particular, its interference with dermal mast cells, were studied in human volunteers. Intradermal injections of 10-100 ng produced dose-dependent flare and itching responses. The cutaneous reactions were inhibited by local administration of the H1 antihistamine mepyramin. The cutaneous responses were also markedly reduced in histamine-depleted skin. These findings indicate that the cutaneous responses produced by PAF-acether were mediated via an indirect and mainly histamine-dependent mechanism.

Adult↗

Failure of mexiletine to relieve severe pruritus.

Mexiletine, an antiarrhythmic drug with pharmacological properties similar to lidocaine, was tested for antipruritic effect in 4 patients with severe pruritus. Although the plasma levels were within the therapeutic range for antiarrhythmic effects, a consistent relief of pruritus could not be found.

Adult↗

The influence of the opiate antagonist naloxone on experimental pruritus.

The antipruritic effect of naloxone hydrochloride was evaluated in a double-blind, cross-over design. Systemic pretreatment with the opiate antagonist did not interfere with the cutaneous itch and flare responses evoked by morphine or histamine, nor did it inhibit the morphine-produced potentiation of the histamine-elicited skin reactions.

Adult↗

Effects of topically applied clobetasol-17-propionate on histamine release in human skin.

The effects of topical glucocorticoid treatment on histamine responses and histamine release induced by the histamine liberating agent compound 48/80 were studied in 17 healthy volunteers. The potent glucocorticoid ointment clobetasol-17-propionate was applied on one upper arm of each individual 14, 4 and 2 hours before testing. The other arm was treated in the same way with the corresponding vehicle. Solutions of histamine and compound 48/80 were injected intradermally in both arms. The size of the flare reaction and the duration of the itch response were recorded. It was found that the flare reactions evoked by histamine were slightly (p less than 0.05) reduced on the steroid-pretreated arm whereas the responses to compound 48/80 were much more suppressed (p less than 0.01). Glucocorticoid treatment did not influence the itch responses to histamine while the itch duration following injection of compound 48/80 was significantly reduced in steroid-treated skin compared to control skin. Our results indicate that topical glucocorticoid treatment can suppress histamine release from dermal mast cells in man.

Adult↗

Impact of topical clindamycin and systemic tetracycline on the skin and colon microflora in patients with acne vulgaris.

In a double-blind study on 20 patients with acne vulgaris, 10 patients were treated with topical clindamycin and 10 patients with oral tetracycline for eight weeks. The skin and colon microflora were determined before, during and up to eight weeks after treatment. All patients improved markedly to the same extent. Topical clindamycin caused no changes in the colon flora, whereas oral tetracycline significantly suppressed the numbers of colon bacteria and four patients were colonized by new tetracycline resistant bacteria. In patients receiving tetracycline, 40% of the skin bacteria became resistant during therapy, while the corresponding figure for clindamycin was 60%. The skin flora was normalized in most patients after the treatment had stopped.

Acne Vulgaris↗

Outdoor and office photochemotherapy of vitiligo: a comparison.

The efficacy of oral trimethylpsoralen photochemotherapy with either natural solar exposures or artificial irradiations was investigated in a group of 63 vitiligo patients. Treatment with outdoor exposures during 2-3 summer seasons was found to be an inadequate therapeutic procedure under Swedish summer conditions. Office treatment with UVA cabins twice weekly led to a better therapeutic response but the number of treatments required for satisfactory repigmentation was high.

Adolescent↗

Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine.

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.

Adolescent↗

Influence of ultraviolet light on itch and flare reactions in human skin induced by histamine and the histamine liberator compound 48/80.

The itch and flare responses induced by intradermal injection of histamine and the histamine liberator compound 48/80 were studied in healthy volunteers before and after exposure to UVB, UVA or PUVA administered 2-3 times weekly for 4 weeks. All three modalities were found to inhibit the responses induced by compound 48/80. The degree of tanning was most pronounced after PUVA and weakest after UVB, without any correlation between tanning and inhibition of itch. In contrast, when induced by histamine, the responses were not inhibited to the same extent, pronounced and significant inhibition being observed only for itching in subjects exposed to UVB. It is concluded that UVB, UVA and PUVA all might be of benefit in treating pruritic states if histamine release is involved and that UVB might have an additional effect by inducing hyposensitivity to itching stimuli.

Adult↗

Histamine release from rat peritoneal mast cells exposed to ultraviolet light.

After irradiation with ultraviolet light, rat peritoneal mast cells incubated with the histamine liberator compound 48/80 were found to have reduced capacity to release histamine. The action spectrum for histamine release inhibition seemed to be in the wavelength region of UVB. UV-light per se did not induce histamine liberation other than for dosages greater than or equal to 1.45 J/cm2. No such release was observed with the doses of UVA studied (3.4-20.5 J/cm2). The metabolic inhibitor 2.4-dinitrophenol (DNP), which almost completely inhibited compound 48/80-elicited histamine release, did not influence the UV-induced histamine release, indicating that the latter was not a secretory process but due to cytotoxic leakage of histamine from the cells. These results suggest that inhibition of histamine-releasing capacity or reduction of skin histamine due to photolysis of mast cells may explain the beneficial effect of UV in pruritic disorders where histamine release from mast cells is involved.

Animals↗