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J Czernielewski

Publications and source records attributed to J Czernielewski.

At least 19 recordsLinked to original sources
PubMed2003

Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas.

BACKGROUND: Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs. METHODS: We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference. RESULTS: In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02). CONCLUSIONS: In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas.

Adolescent↗
PubMed2001

Adapalene biochemistry and the evolution of a new topical retinoid for treatment of acne.

The emergence of oral and topical retinoids was a major advance in the clinical management of acne vulgaris. However, the benefits of these agents were somewhat limited by the degree of side effects caused by these drugs. Over the last 15 years, researchers have sought compounds that can provide the manifold therapeutic benefits obtained with tretinoin and isotretinoin while minimizing the potential for irritation and other unwanted effects. Adapalene, a naphthoic-acid derivative, is one result of this search, and it serves as an example of rational drug development: the formulation of a novel substance with specific pharmacological properties and clinical objectives in mind. These goals included enhancing stability, enhancing anti-inflammatory effects, maintaining effectiveness and minimizing cutaneous irritation. This paper reviews the history of the development of adapalene, its unique physical and biochemical properties, and the pharmacological studies that demonstrate a wide range of retinoid-receptor, genetic and anti-inflammatory effects, all of which contribute to the therapeutic efficacy and improved tolerability of adapalene observed in the clinical use of this agent for the treatment of acne.

Acne Vulgaris↗
PubMed2000

A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region.

In view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological-clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26. 4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35.0%) in the AT6 group, 11 of 40 (27.5%) in the AT12 group and seven of 41 (17.1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44.0% (22 patients) in the AT6 group, 72.3% (34 patients) in the AT12 group and 37.5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.

Adult↗
PubMed1997

Adapalene 0.1% gel has low skin-irritation potential.

BACKGROUND: Adapalene is a new naphthoic acid derivative with potent retinoid and antiinflammatory properties, developed for the topical treatment of acne vulgaris. OBJECTIVE: We compare the cutaneous safety of adapalene in different gel vehicles with tretinoin 0.025% gel. METHODS: A total of 42 healthy human subjects were enrolled in two randomized, double-blind, controlled, intraindividual studies. In the first study (study A), adapalene aqueous 0.03% and 0.1% gels were evaluated for their 21-day cumulative irritation potential compared with vehicle alone, patch alone, and tretinoin 0.025% gel under occlusion. In the second study (study B), adapalene aqueous (0.03% and 0.1%) gels and adapalene alcoholic (0.03% and 0.1%) gels were evaluated for their 5-day cumulative irritation potential compared with their respective vehicles and tretinoin 0.025% gel. Transepidermal water loss (TEWL) was measured daily at each visit. RESULTS: In study A, adapalene had a slight irritation potential that was in the same range as the gel vehicle and the patch alone, whereas tretinoin 0.025% gel was a severe irritant. In study B, no irritation was seen with either adapalene aqueous gels or adapalene gel vehicles or patch alone. The adapalene alcoholic gels were slightly irritating, and tretinoin gel produced intense irritation reactions in the majority of subjects. TEWL increased fourfold at the tretinoin site but remained unchanged at all adapalene sites. CONCLUSION: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel.

Adapalene↗
PubMed1997

Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients.

BACKGROUND: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris. METHODS: A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products. RESULTS: A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported. CONCLUSION: The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.

Acne Vulgaris↗
PubMed1997

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Adapalene↗
PubMed1996

A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial.

BACKGROUND: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. OBJECTIVE: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris. METHODS: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. RESULTS: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. CONCLUSION: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Acne Vulgaris↗
PubMed1996

[Comparative study of the efficacy and tolerability of 0.1 and 0.03 p.100 adapalene gel and 0.025 p.100 tretinoin gel in the treatment of acne].

INTRODUCTION: Adapalene is a new chemical entity with retinoid activity. PATIENTS AND METHODS: 0.1 p. 100 adapalene gel (Différine gel), 0.03 p. 100 adapalene gel and a commercially available 0.025 p. 100 tretinoin gel (Aberel gel) were compared in 89 male and female patients with acne. RESULTS: Inflammatory, non inflammatory, total lesion counts, and the global facial acne grade regularly decreased as a function of time in the three treatment groups. No statistically or clinicaly significant differences were observed for these parameters between 0.1 p. 100 adapalene gel and 0.025 p. 100 tretinoin gel following a 12-week treatment. Conversely, both of these gels were significantly more effective than 0.03 p. 100 adapalene gel with regards to inflammatory and total lesion counts, and the global facial acne grade. The differences of efficacy seen between both adapalene gels demonstrate a dose-dependent activity of the drug in the topical treatment of acne. The three products induced retinoid-like skin irritation with significant differences in intensity in favour of adapalene for erythema, dryness, scaling and burning after application and in favour of tretinoin for persistent burning. No treatment-related medical events were reported and adapalene plasma levels were lower than 0.15 ng/ml (limit of detection of the analytical method). CONCLUSIONS: The topical treatment of acne with adapalene gels was found to be safe and effective, with a dose-related response. The efficacy of 0.1 p. 100 adapalene gel and of 0.025 p. 100 tretinoin gel are not different but skin tolerance of 0.1 p. 100 adapalene gel is superior.

Acne Vulgaris↗
PubMed1994

Chronic topical application of all-trans-retinoic acid in man does not affect corneocyte surface area.

The potential therapeutic activity of topically applied novel analogues of retinoic acid is currently measured in many different animal models. In most cases, the technique used is invasive and biopsy specimens are required. Furthermore, efficacy in these models is not a guarantee of success in treatment of humans. Therefore, predictive human pharmacology tests are required in order to quantify a retinoid effect on human skin before conducting large clinical trials. The aim of this study was to determine whether changes in corneocyte surface area could be used as a predictive measure for the efficacy of topical retinoids in man. Topical applications of all-trans retinoic acid gel (Aberel), salicylic acid gel and the gel vehicle were made once daily for 4 weeks to skin of the lumbar region of healthy human volunteers. Corneocytes were recovered from these three treated zones as well as from one zone of untreated skin, and their surface areas were measured by image analysis using a MOP-Videoplan. The results showed that at no point during the 4 weeks of daily application to healthy human skin was there a statistically significant difference in the surface area of corneocytes recovered from Aberel, salicylic acid-, vehicle-treated or untreated sites. No specific effect of retinoic acid could be detected. However, although no between-treatment differences were found, significant cyclical changes in the mean surface areas with respect to baseline were observed.

Administration, Topical↗
PubMed1993

Migration of Langerhans cells into human epidermis of "reconstructed" skin, normal skin, or healing skin, after grafting onto the nude mouse.

Human skin equivalents composed of keratinocytes cultured on a lattice constituted of human fibroblasts embedded in type I collagen were grafted onto the nude mouse. It is demonstrated, by indirect immunofluorescence and electron microscopy, that, after grafting, mouse Langerhans cells migrate into the human epidermis. Human Langerhans cells are not present in this system. In split-thickness human skin grafts, at long periods (5 and 12 months) after transplantation, a progressive migration of murine Ia(+) cells in the human epidermis and the presence of human Langerhans cells were shown by indirect immunofluorescence. Creation of a wound at the center of the grafted human skin and identification of the Langerhans cell origin shows a repopulation with human Langerhans cells provided the injury was performed early (2 months) after grafting. Injury at a later stage (5 months) resulted in presence of both human and murine Langerhans cells. These observations show 1) that, after grafting of "reconstructed" human skin or of split-thickness human skin onto nude mice, mouse Langerhans cells migrate into the grafted human epidermis; and 2) that the Langerhans cells repopulating a healing grafted epidermis devoid of Langerhans cells derived from the non-injured surrounding epidermis. The present work thus shows that besides bone marrow, lymph nodes, or/and spleen, surrounding cutaneous regions can also serve as sources of Langerhans cells.

Animals↗
PubMed1993

The vellus hair follicle in acne: hair growth and sebum excretion.

In this study we investigated the activity of the vellus hair follicle in acne. Hair growth and sebum excretion in vellus hair follicles were measured on the forehead and back of men, and on the forehead, cheek, and back of women with acne. Hair growth was assessed by computerized image analysis (phototrichogram), and sebum excretion by computer analysis using Sebutape. In patients with acne, marked differences were revealed when results were compared with recent data from healthy persons. In particular, the mean growth rate of vellus hairs was higher, whereas the percentage of anagen hairs was lower, and the duration of the anagen phase shorter in patients with acne than in healthy individuals. Hair growth and sebum excretion depended significantly (P < 0.01) on the anatomical site (forehead 414 hairs/cm2, 0.053 mm/day, 34%; back 93 hairs/cm2, 0.16 mm/day, 21%). In addition, analysis of hair growth revealed significantly higher values in females than in males for (i) percentage of anagen hairs (P > 0.01), (ii) for vellus hair length (P < 0.05), and (iii) for the duration of the anagen phase (P < 0.01). The present study demonstrates that the activity of the vellus hair follicle is influenced by acne, and vice versa, and therefore its role in the aetiopathogenesis of acne should be reconsidered.

Acne Vulgaris↗
PubMed1993

Topical retinoids. Their uses in dermatology.

The retinoids provide an important new way of treating dermatologic disorders. They have also proved to have a role in the prevention of new lesion formation. New retinoids, of which adapalene is one, have recently been synthesized in order to obtain similar or better efficacy while reducing skin irritation potential. These new molecules are currently under clinical investigation. Preliminary results are encouraging. In the near future, an expanded range of topical retinoids should be available.

Adapalene↗
PubMed1992

Migration of Langerhans cells into the epidermis of human skin grafted into nude mice.

In a previous study, it was demonstrated that human Langerhans cells (LC) are preserved in human skin grafted onto a nude mouse. Moreover, although it was observed that mouse LC of the host invade skin grafts from allogeneic mouse or rat, they do not penetrate in human skin grafts. In most of the human skin equivalent systems produced in vitro, LC appear to be lost. The present study was designed to investigate whether the mouse LC will repopulate a human skin equivalent. For this purpose, two different systems of skin equivalent have been grafted into the nude mouse. They were composed of human keratinocytes deposited on dead human dermis, or on lattice composed of human fibroblasts embedded in type I collagen. At different times after grafting, the presence of LC in the transplants was assayed either by indirect immunofluorescence or by electron microscopy. Indirect immunofluorescence was performed on frozen sections or on epidermal sheets with anti-Ia, anti-HLA-DR, or OKT6 antibodies. It was observed that, at 2 months after grafting, Ia(+) HLA-DR(-) OKT6(-) cells are present in grafted human epidermis. Moreover, LC with typical Birbeck granules are also detected by electron microscopy. It could be concluded, from this study, that mouse LC can repopulate human epidermis devoid of human LC.

Animals↗
PubMed1991

Processing and statistical analysis of laser Doppler data applied to the assessment of systemic anti-inflammatory drugs.

Continuous laser Doppler measurements of methyl nicotinate-induced skin inflammation have been used to evaluate the activities of three oral non-steroidal anti-inflammatory drugs, indomethacin 50 mg (Indocid), tiaprofenic acid 100 mg (Surgam) and sodium acetylsalicylate 1 g (Catalgine). They were compared in a single-blind, randomized, intra-individual comparison (N = 16) versus placebo (lactose). One hour after each drug was ingested, four concentrations of methyl nicotinate were applied to the subject's forearms. Simultaneous skin blood flow (SBF) measurements were then carried out on the four tested zones, by use of four calibrated laser Doppler flowmeters. Computerized processing of recorded SBF levels provided data related to flow amplitude, kinetics and magnitude (area under the curve) of the reactions. A detailed statistical analysis was performed to establish the selectivity of this type of test and the following points were demonstrated: adjustment of SBF data to baseline did not improve precision, data had to be log-transformed before analysis, and magnitude data gave the best product discrimination. Under the conditions of this study, i.e. one hour after oral administration and for the indicated doses, the tested products could be classified, in terms of anti-inflammatory activity, as follows: Lactose less than Indomethacin 50 mg = Tiaprofenic acid 100 mg less than Sodium acetylsalicylate 1 g.

Adult↗
PubMed1991

Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris.

CD 271, a naphthoic acid, is a powerful modulator of epidermal differentiation. This double-blind, randomized study compared the efficacy and safety of two concentrations (0.03% w/w and 0.1% w/w) of CD 271 alcoholic gel, with 0.025% w/w tretinoin gel in 72 male patients with acne vulgaris over a period of 12 weeks. Efficacy was measured by counting facial inflammatory and non-inflammatory lesions and by grading the severity of the acne at each visit. Skin tolerance was assessed with subjective symptoms, such as burning and pruritus, as well as clinical assessment of erythema, dryness and scaling on the treated areas. The alcoholic 0.1% CD 271 gel was as effective as 0.025% tretinoin gel in reducing total comedone counts (83% reduction for both products after 12 weeks' treatment). The reduction in the number of inflammatory lesions and the total number of acne lesions were significantly greater with 0.1% CD 271 gel than with tretinoin gel (69% and 79% for 0.1% CD 271, 50% and 73% for tretinoin gel, respectively, P less than 0.05). All three treatments were well tolerated and there were no changes in any major blood parameters. No CD 271 could be detected in blood plasma at the end of the study (detection limit = 1 ng/ml).

Acne Vulgaris↗
PubMed1991

Sequence of morphological events during topical application of retinoic acid on the rhino mouse skin.

In a study of the comedolytic action of retinoids on the epidermal pseudocomedones of rhino mouse skin, the earliest changes and the sequence of events induced by the treatment were investigated. Rhino mice were treated topically with all-trans retinoic acid and at various time intervals from day 0 to 3 weeks, histological and ultrastructural studies as well as quantification of mast cells were performed. The earliest changes occurred in the dermis after 2 days of treatment and were characterized by degranulation of mast cells, clumping and association of Langerhans cells and lymphocytes. During the second week of treatment there was hyperplasia, hypergranulosis and an increase in the number of membrane coating granules with disorganization of the horny layer both of the epidermis and the follicular epithelium. These changes in the proliferation and the differentiation of keratinocytes resulted in a comedolytic effect. Associated with these epidermal changes there were changes in the dermis with an increased number of mast cells and a decreased number of Langerhans cells.

Acne Vulgaris↗