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Biomedical subjects

O Hägermark

Publications and source records attributed to O Hägermark.

At least 19 recordsLinked to original sources
PubMed1995

Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects.

To explore the pruritogenic and inflammatory effects of cytokines, a single dose of 20 micrograms recombinant human interleukin-2 was injected intradermally into eight patients with atopic dermatitis and eight healthy controls. The study was double-blind and randomized with glucose as a negative control. The effects were evaluated by recording local itch and erythema over 72 h and by examining skin biopsies taken at 24 h and 72 h. In patients and controls, interleukin-2 provoked a low-intensity local itch with maximal intensity between 6 h and 48 h and erythema with maximal extension between 12 h and 72 h. In the atopic dermatitis patients, these reactions tended to appear earlier and were less pronounced than in the healthy controls. Interleukin-2 induced dermal mononuclear cell infiltrates consisting mainly of CD3+ cells. A majority of the T cells were CD4+. The number of dermal CD25+, HLA-DR+ and ICAM-1+ cells was also increased at the interleukin-2 induced spongiosis and exocytosis as well as HLA-DR+ and ICAM-1+ keratinocytes. The microscopic findings tended to be more prominent at 72 h than at 24 h in both groups, but with a somewhat slower onset in the atopic dermatitis patients. In conclusion, a single intradermal injection of interleukin-2 induced local itch, erythema, dermal T-cell infiltrates, spongiosis, exocytosis and activation of keratinocytes both in atopic dermatitis patients and in healthy controls.

Adult↗
PubMed1992

Some methods for evaluating clinical itch and their application for studying pathophysiological mechanisms.

Research on itch has been hampered by difficulties in measuring the itch sensation. A microcomputer-based system, where the patients themselves record their symptoms on portable data loggers can be used for quantitative measurements of clinical itch and for the detection of antipruritic effects of drugs. By using this system we have found that itch in atopic dermatitis is not inhibited by antihistamines but by cyclosporin A, a drug inhibiting cytokine production. Thus histamine is not a major pruritogen in atopic dermatitis. A hypothesis is proposed that cytokines are involved in itch in atopic dermatitis.

Administration, Topical↗
PubMed1992

Peripheral and central mediators of itch.

Since the majority of itching skin diseases are inflammatory or allergic, it has been assumed that release or activation of inflammatory mediators, stimulating the itch receptors, play an essential role in the pathophysiology of itch. In this review some of the possible mediators are discussed. Histamine induces itch upon intradermal injection, but urticaria is the only itching dermatosis which is significantly relieved by antihistamines. Serotonin is much weaker than histamine in provoking itch upon intradermal injection. Serotonin acting in synergism with prostaglandins may cause itch in polycythaemia vera. Neuropeptides release histamine from skin mast cells, but it remains to be determined whether neurogenic peptides are responsible for clinical pruritus. Prostaglandins enhance pruritus induced by intradermal histamine (and serotonin) but are weak pruritogens per se. Lymphocytes are present in many itching skin diseases and it could be assumed that lymphokines are involved in the pathogenesis of itch. Supporting this theory is the finding that ciclosporin A, an inhibitor of lymphokine production, reduces itch in atopic dermatitis. Central mechanisms are essentially unknown, but there are indications that opioid peptides might be involved in the central transmission of itch.

Eicosanoids↗
PubMed1992

Inhibitory effect of loratadine and clemastine on histamine release in human skin.

The inhibitory effect of the two H1 antagonists clemastine and loratadine on histamine release in human skin was studied in 15 volunteers. The antihistamines and placebo were administered orally (clemastine 2 mg twice a day, loratadine 10 mg once a day) for 5 days according to a double-blind, crossover design. Clemastine caused a significant sedation in comparison with placebo, whereas there was no difference between loratadine and placebo in this respect. After 5 days' medication, flare reaction was induced by intradermal injection of histamine and the histamine liberator compound 48/80. The antihistamine dosages were approximately equipotent and inhibited the flare response induced by histamine to about the same extent, whereas the flares induced by compound 48/80 were still more inhibited by both drugs. The results indicate that clemastine and loratadine not only inhibit histamine effects at H1 receptor level, but have additional suppressive effects, probably due to inhibition of mast cell degranulation. The simple, virtually noninvasive, in vivo technique described in this paper does not require chemical analysis of the released mediators and could be used to screen 'mast cell stabilizing' effects of various antihistamines.

Adolescent↗
PubMed1991

Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine.

The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H1-receptor antagonism was estimated as the reduction in the area of the flare and the duration of the itch after intradermal injection of histamine 0.1 and 1.0 micrograms. CNS effects were assessed by a battery of computerized neuropsychological tests and seven visual analogue scales. Drug compliance was ascertained by plasma level determinations. Cetirizine 10 mg (SOD) produced a more pronounced peripheral effect than 20 mg hydroxyzine, whereas hydroxyzine but not cetirizine, showed a significant sedative action in the relevant rating scales. These effects vanished during steady state, suggesting adaptation to the initial sedative effect of hydroxyzine in most of the subjects. No sedative effect of cetirizine was demonstrated. There was no impairment at group level in the neuropsychological tests after the SOD or SS treatment. However, six subjects who showed sedation in the analogue ratings after hydroxyzine, displayed significantly impaired performance after hydroxyzine SOD. The findings are discussed in relation to the individual characteristics of the study groups.

Administration, Oral↗
PubMed1991

Patients' perception of itch induced by histamine, compound 48/80 and wool fibres in atopic dermatitis.

Itch and flare responses were investigated in 32 patients with atopic dermatitis (AD) and in 32 healthy controls. Itch was induced chemically by intradermal injections of histamine (1, 3.3, 10 and 100 micrograms/ml) and compound 48/80 (10 micrograms/ml) into non-lesional skin and mechanically by wearing a woollen sweater. Continuous recording of itch intensity allowed the calculation of itch duration (ID), maximal itch intensity (Imax) and a "total itch index" (Tii). The itch responses were significantly increased in AD patients compared with controls for wool fibres and one of the histamine concentrations (10 micrograms/ml), but not for the remaining three histamine concentrations or compound 48/80. Conversely, the flare response was significantly smaller in AD patients than in controls for the two strongest histamine solutions and compound 48/80. Significant dose-response relationships were found between histamine concentration and each of ID, Imax, Tii and flare in both patients and controls. The slope of the flare-regression line was significantly steeper in controls than in AD patients, whereas the slopes of the itch-regression lines did not differ significantly between the two groups, i.e. their ability to discriminate between weak and strong histamine concentrations did not differ significantly. No increased skin mast cell releasability in vivo to compound 48/80 was shown in AD patients compared with controls. The itch and flare responses of AD patients did not correlate significantly with clinical itch intensity, eczema score or serum IgE level.

Adolescent↗
PubMed1990

The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitis.

A double-blind, randomized, cross-over study was carried out on the effect of a sedative and a non-sedative antihistamine on 25 adults with atopic dermatitis. Intensity of itch was recorded using a computerized method for self-assessment (Pain-Track) and using conventional visual analogue scales. The antipruritic effect of 3 days of treatment with the non-sedative H1 antagonist terfenadine (60 mg b.i.d.) and with the sedative antihistamine, clemastine (2 mg b.i.d.) did not differ from that found with the placebo. Our findings support the view that histamine is not of importance in the pathogenesis of itch in atopic dermatitis.

Adolescent↗
PubMed1990

Antipruritic effect of oral cyclosporin A in atopic dermatitis.

The effect of ten days' treatment with cyclosporin A, 5 mg/kg/day, in 10 adults with atopic dermatitis was investigated using a double-blind, randomized, placebo-controlled, cross-over design. Evaluation was based on itch recording, clinical scoring and immunohistochemical examination of skin biopsy specimens. Cyclosporin A significantly reduced the itch intensity, the eczema score and the consumption of topical hydrocortisone. A significant decrease in serum magnesium and in the total number of blood eosinophils was seen. No other laboratory abnormalities were observed. In lesional skin, Cyclosporin A induced a relative decrease of CD3+ T cells in 5/10 patients, of HLA-DR+ cells in 6/10, and of interleukin-2-receptor positive (CD25+) cells in 4/10. However, these changes in phenotype expression did not seem necessary for itch relief. Relapse of clinical symptoms was seen within 2-30 days of completion of the Cyclosporin A course. The mechanism of the antipruritic effect remains unclear, but the present findings may support the hypothesis that 'pruritogenic cytokines', whose production is inhibited by Cyclosporin A, may be important in the pathogenesis of itch in atopic dermatitis.

Administration, Oral↗
PubMed1989

Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching.

Adult↗
PubMed1989

Some aspects of the experimental induction and measurement of itch.

Two different rating scales--a visual analogue scale (VAS) connected to a chart-recorder, and Pain-Track, a micro-computerized system with a 7-step-graded, fixed-point, non-verbal scale (FPNVS)--were evaluated for their capacity to assess experimental, histamine-induced itch continuously in 38 healthy subjects. The consequences for itch perception of using different injection sequences of various histamine concentrations were also investigated. A linear dose-response relationship was shown with random injection order for all subjective variables studied (itch latency and duration, maximal itch intensity, 'total itch index') with the VAS, but only for itch duration and 'total itch index' with the FPNVS. Using the VAS and injecting histamine solutions with increasing concentration, a significant dose-response curve was obtained for maximal itch intensity and 'total itch index', but when the same histamine stimuli were presented in the reverse (i.e. decreasing) order, there was no dose-response relationship. This indicates that central nervous system interaction may be unequally activated, depending on the order of different injected histamine stimuli. The objective variable flare was unaffected by the injection sequence. It is concluded that random injection order should be used in the assessment of itch sensation, in order to avoid systematic errors. The fact that the FPNVS did not discriminate as well as the VAS could indicate that our experimental stimuli were too weak to be properly discriminated with a 7-step-graded scale.

Adult↗
PubMed1989

Computerized recording of itch in patients on maintenance hemodialysis.

Itch was assessed both continuously using a computerized method, Pain-Track, and retrospectively using visual analogue scales (VAS) by 28 patients undergoing maintenance hemodialysis and suffering from uremic pruritus. Measurements were performed during 7 consecutive days including three dialysis sessions. Pain-Track recordings showed that itch intensity was greater during dialysis than on days following dialysis (p less than 0.05). Possible explanations are that pruritogenic substances might be released during treatment or that removal of such substances during dialysis leads to amelioration of symptoms after treatment. Alternatively, lowering of the sensory threshold due to general discomfort in association with dialysis may exacerbate the itch intensity. There was no consistent difference between daytime and bedtime itch scores over the week, except on the second day without treatment, when bedtime itch ratings significantly exceeded those during the day (p less than 0.05), suggesting that factors other than inactivity are essential for this peak in itch intensity. Thus, after 2 days without treatment, when patients become increasingly metabolically deranged, they reported maximal itch, implying that the accumulation of pruritogenic substances is of major importance in the pathogenesis of uremic pruritus. There was a positive correlation between Pain-Track and VAS data, although significant fluctuations in itching could be detected only with Pain-Track.

Adult↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1986

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↗