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Biomedical subjects

D Van Neste

Publications and source records attributed to D Van Neste.

18 recordsLinked to original sources

Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substance P.

The skin vascular responses (weal, flare, blood flow measurements) elicited by intradermal administration by pricking of histamine (HS) and substance P (SP) were evaluated 6 h after a single intake of anti-H1 agents displaying different activity profile on skin tests at currently recommended dosages (loratadine 10 mg, cetirizine 10 mg) as compared to placebo (P). The weal and flare response and the increases of blood flow occurring in the usual flare area after HS and SP were almost completely abolished by cetirizine. Inhibition of HS- and SP-induced weal and flare reactions was less marked after loratadine and blood flow in the expanding flare after HS and SP showed significant fluctuations over time. In view of the present results and of data obtained in previous experiments with intradermal injection of agonists, we hypothesize that mode of administration of agonists significantly influences the size of the residual weal after anti-H1 agents. We demonstrate that SP weals induced by pricking are largely inhibited by a potent H1 blockade which supports the view that this phenomenon, as well as the SP-flare, is due to SP-induced histamine liberation. We also, for the first time, report on fluctuations recorded at the edge of the developing flare with laser Doppler flowmetry early after prick testing with a weak H1 blockade. This opens up new avenues in dynamically testing H1-receptor occupancy in vivo and in situ in human skin.

Adult

Comparative study of normal and rough human skin hydration in vivo: evaluation with four different instruments.

Appropriate monitoring of skin hydration during clinical and/or experimental trials needs devices with acceptable reproducibility and sensitivity under conditions ranging from increased, and normal to low hydration. The aim of this study was to compare the variation of electrometric data generated by 4 different instruments (Skicon Hygrometer, 2 CM420 and a CM820 corneometer) in normal and experimentally damaged skin displaying surface roughness. Rough skin sites were observed during the healing process after repeated tape stripping of stratum corneum in humans (e.g. 10-14 days after insult). They displayed lower conductance and or capacitance levels as compared to normal skin sites of the same subjects. The Skicon hygrometer showed higher variability as compared to the corneometers and was less sensitive, in relative terms, in the rough skin sites. This device also showed a moderate zero drift and re-zeroing was repeatedly utilized during the experiment. When the corneometer data were plotted against the hygrometer data, the slope of the regression line generated by the CM420a was different from CM420b and from CM820; the two latter were not significantly different from each other. Hence, comparison of absolute data obtained under comparable conditions (in this case CM420a and CM420b) in a single laboratory should not be made without prior calibration. Standards for evaluating interinstrumental variation are currently unavailable. This aspect of the measurement of electrical properties of the skin has not been investigated in great detail and has often been neglected in the past. Our findings also indicate that a constant control over the performances of a particular device should further improve the reliability of the data.

Adult

Skin response to histamine. Reproducibility study of the dry skin prick test method and of the evaluation of microvascular changes with laser Doppler flowmetry.

The author presents original data obtained when using the dry skin prick test method to introduce histamine into the skin and by non-invasive evaluation of the skin blood flow changes at various sites/times during the development of the weal and flare reaction. The test method (1-second prick test duration and evaluation with laser Doppler flowmetry) generated reproducible responses when repeated in the same group of subjects (n = 10). At predefined fixed skin locations within the histamine-induced flare reaction area increased volumes of skin blood flow were recorded. When similar locations were explored after the control prick test, there were only minimal changes in skin blood flow. Pooled data recorded at four different sites located 1 cm from prick sites showed minimal variation and skin perfusion volumes were greater than basal values. The development of the histamine-dependent weal in its early phase (9th min) was associated with slightly smaller numbers of skin blood perfusion units, compared with recordings made during the 15th min. The control prick tests showed slightly higher levels at 9 min than at 15 min. This inverse relationship might be useful to quantify the histamine-specific changes in skin blood flow. These data also clearly illustrate that it is mandatory to state the precise place of measurement and time after challenge when reporting on instrumental evaluation of the skin response to histamine.

Adult

Skin response to histamine dry skin prick test: influence of duration of the skin prick on clinical parameters and on skin blood flow monitoring.

This comparative trial (histamine dry skin prick test versus control prick test) evaluates with subjective and objective clinical methods (i.e. itch scores, wheal area, and wheal and flare area) and with laser Doppler flowmetry (multiple sites measured between 5 and 15 min after prick test) the effect of increasing the duration of the skin prick (1, 3 and 10 s). As compared with control prick tests, all objective clinical parameters after histamine prick test were significantly different from the control prick tests. There was no interaction between agonist-duration of prick test and clinical parameters. When present, itch was reported only after histamine prick test. Skin blood perfusion values were evaluated with Laser Doppler flowmetry at prick test sites and at 1 cm distance from the prick test site. At control and histamine prick test sites, increased blood flow values were observed and a moderate interaction between agonist-duration of prick test and repeated measurement was noted (one tail P less than 0.05); there were indeed lower values 9 min after histamine prick tests whatever the duration of the prick test. At 1 cm distance from histamine prick test sites, all skin perfusion measurements (either 5-8 or 11-14 min) showed increased values over data recorded after control prick test (P less than 0.0001). On pooled data recorded at distance from histamine or control prick tests, there was a significant interaction between agonist-duration of prick test and laser Doppler flowmetry (P less than 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity

Pharmacological modulation by cetirizine and atropine of the histamine- and methacholine-induced wheals and flares in human skin.

This study was planned to verify whether different methods for the measurement of skin reactivity, i.e. wheal and flare area, wheal thickness, skin capacitance and transepidermal water loss, were or were not able to discriminate between intradermally injected agonists (histamine and methacholine). For evaluating agonist/antagonist interactions, we adopted a cross-over, double-blind, placebo-controlled study designed to compare the effects of cetirizine and atropine. The intradermal injection of agonists elicited the appearance of wheal and flare reactions and, after histamine, the skinfold thickness was significantly increased. Skin capacitance and transepidermal water loss measurements reflected sweat gland activation after methacholine injection but were, respectively, not or less affected by histamine dry skin prick test or saline; hence, both methods appear very sensitive for in vivo testing of cholinomimetic agents. Cetirizine inhibited all the specific skin modifications induced by histamine challenge, wheals, flares and increased thickness, without affecting the methacholine-induced perspiration. This would further support the H1 specificity of this anti-H1 agent in vivo. However, at the agonist/antagonist ratios tested in view of the safety of the test persons, we were unable to objectivate methacholine blockade by atropine.

Adult

Inhibition of the cutaneous response to histamine by H1-blocking agents. Quantitative evaluation of microvascular changes in the skin after histamine challenge and a comparison of the effects of a single intake of cetirizine and terfenadine.

A controlled, randomized, double-blind, cross-over study was performed in 10 healthy volunteers in order to compare changes of cutaneous blood flow values (CBFV, laser Doppler flowmetry, Periflux, Perimed, S) in histamine-challenged skin before and after administration of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. The overall pattern of the basal cutaneous wheal and flare response to the agonists (histamine: aqueous solution: Hsol, or Phazet: Hprick) and control saline solution, showed the expected range of clinical effects, i.e. Hsol greater than Hprick greater than saline. Similarly, the increase of CBFV on the flare area was higher around the histamine injections as compared with saline. Surprisingly, CBFV was decreased at the site of Hsol and Hprick injections as compared with the levels recorded at the control injections. The following changes were noted after intake of H1-blocking agents. (1) There was a reduction of the areas of wheal and flare at all injection sites after administration of the H1 blockers, this reduction being consistently greater under cetirizine than terfenadine. (2) CBFV, measured 1 cm from the site of Hsol injection (i.e., within the area of normal flare response), was decreased only with cetirizine. In the smaller flare area induced by Hprick, CBFV was equally suppressed by both drugs. (3) At the site of agonist injection, along with a reduction of the size of the wheal, we observed significant increases in CBFV after drug intake. Under these experimental conditions, this quantitative pharmacologic in vivo assay of agonist-antagonist interactions suggests that after initial administration of normally prescribed doses, cetirizine may possess more anti-H1 activity than terfenadine.

Adult

Imidazoles and benzoyl peroxide: a comparative trial of two treatment schedules.

A double-blind, split-face, self-controlled pilot trial was designed for comparing the therapeutical effect of (a) combination of 2% miconazole nitrate and 5% benzoyl peroxide applied twice daily and (b) topical application of 1% isoconazole nitrate in the morning followed in the evening by 5% benzoyl peroxide. There were no clinically relevant differences between both treatment regimes. These results are interpreted in terms of bioavailability of the active substances.

Acne Vulgaris

[Biological behavior of Sarcoptes scabiei var. suis in swine epidermis. A scanning electron microscopy study in hyperkeratotic (or Norwegian) scabies of swine].

The behaviour of Sarcoptes scabiei var. suis has been studied in hyperkeratotic scabies of pigs (fig. 1). The scanning electron microscope enabled us to observe the outer surface of the eggs in the burrow and even within the cut body of the fertilized female mite (fig. 2). Early events during hatching of the eggs and the first steps of the newborn larva (fig. 3) are shown. The presence of crystals containing calcium and phosphate is shown to occur in places where huge amounts of faecal material are collected (fig. 4). Although some of these aspects have not been published previously we observed many similarities in behavior between Sarcoptes scabiei var. hominis and suis in their respective hosts affected with hyperkeratotic scabies. As to the therapeutic aspect of scabies in humans, carefully selected drugs currently used in the systemic treatment of scabies in pigs would be worth a trial in patients difficult to treat.

Animals

Hyperkeratotic (Norwegian) scabies and onychomycosis in an immunosuppressed patient.

Hyperkeratotic scabies and onychomycosis were associated in an immunosuppressed patient. Onychomycosis healed spontaneously after treatment of scabies. A possible interrelationship between Sarcoptes scabiei infestation of the hyponychium and dermatophytes infestation of the nail plate could be responsible for this peculiar evolution.

Adrenal Cortex Hormones

Immune complex disease associated with Peroben intake.

The clinical history and biological investigations of a patient presenting an immune complex disease induced by Peroben are reported. Biological signs were those of a drug-induced lupus syndrome. A provocation test allowed disclosure of its pathomechanism, since during Peroben intake a high C1q binding activity occurred and later regressed, while deposits of IgM and C3 were evidenced in the vessel walls. Complete or partial thrombosis succeeded accompanying a leukocytoclastic vasculitis.

Adult

[Atopic dermatitis: a histologic and radioautographic study (after 3H-thymidine labelling) of epidermal and dermal lesions (author's transl)].

Skin lesions of atopic dermatitis (A. D.) have been studied histologically and radioautographically after in vitro incorporation of tritiated thymidine. The histopathologic aspects of epidermis in the different types of skin lesions are reviewed. The dermal infiltrate is mononuclear and not very abundant in all types of lesions. An enlargement of the epidermal proliferative compartment has been noticed. Labelled cells are distributed as follows (mean +/- standard deviation) : 46 +/- p. 100 in the basal layer; 37 +/- 6 p. 100 in the epibasal layer; 16 +/- 7 p. 100 in the upper layers. The basal and epidermal labelling indices have been found significantly increased in exudative and lichenified lesions as compared to xerotic areas and normal epidermis. The labelling index of the "round" cell infiltrate in the dermis was significantly higher than in irritant patch test reactions (p less than 0.001) but significantly lower than in allergic positive patch test reactions (p less than 0.001). This increased cell proliferation in the dermal infiltrate does not allow definite conclusions about immunopathogenesis of the disease: indeed, a large number of mediators, involved in the inflammatory reactions of A. D. lesions, can modulate cell proliferation.

Adolescent