Search PubMed⌕ Search

Biomedical subjects

K Thestrup-Pedersen

Publications and source records attributed to K Thestrup-Pedersen.

At least 19 recordsLinked to original sources
PubMed2006

Update on the use of ciclosporin in immune-mediated dermatoses.

Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.

Arthritis, Psoriatic↗
PubMed2005

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Anti-Inflammatory Agents↗
PubMed2005

Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis.

BACKGROUND: A standardized instrument is needed to rate the overall severity of chronic hand dermatitis (CHD), in particular during clinical trials. OBJECTIVES: To design and validate a photographic guide. METHODS: Initially, five experts were asked to grade 50 photographs of CHD, first individually, then as a consensus-building group, in order to select the photographs included in the guide. Then, a validation session with 11 different dermatologists evaluating 28 patients was conducted to assess the interrater reliability and test-retest reproducibility of the assessment of disease severity, relying on the photographic guide, on two consecutive days. Patient order was randomized, and only diseased hands were visible to prevent any bias in evaluation. RESULTS: The experts reached a consensus for development of a photographic guide composed of five severity levels and four photographs per severity level. Results of the validation session showed a high level of interrater reliability and test-retest reproducibility. CONCLUSIONS: The photographic guide is a reliable tool for assessing the morphological severity of hand dermatitis, and can be used as part of a comprehensive evaluation of disease in international multicentre clinical trials.

Adult↗
PubMed2005

Cutaneous immunological activation elicited by a low-fluence pulsed dye laser.

BACKGROUND: Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes. MATERIALS AND METHODS: Eight healthy adult volunteers (mean age 56.3 years, range 25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction. RESULTS: Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects. CONCLUSION: The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.

Adult↗
PubMed2004

The role of topical calcineurin inhibitors in atopic dermatitis.

For more than five decades, topical corticosteroids and emollients have been the mainstay of therapy for atopic dermatitis. However, the potential for side-effects limits the clinical utility of corticosteroids in providing long-term disease control. With a unique mode of action that differs from that of corticosteroids, the steroid-free topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, provide skin-selective treatment that targets key factors involved in the pathogenesis of this chronic disease. An extensive series of clinical trials involving more than 16,000 patients with predominantly moderate to severe atopic dermatitis in tacrolimus studies and over 2000 patients with primarily mild to moderate disease in pimecrolimus studies has shown that both TCIs provide effective and well-tolerated treatment for atopic dermatitis. Randomized controlled trials have demonstrated that tacrolimus is superior to conventional hydrocortisone-based regimens and does not cause skin atrophy or other steroidal side-effects. Both tacrolimus and pimecrolimus prevent disease flares and provide progressive and sustained disease improvement with long-term therapy. These and other clinical benefits of TCIs are discussed, together with the safety profiles of tacrolimus and pimecrolimus and their use in clinical practice. In addition, this review summarizes findings from the many trials carried out with these agents and outlines how TCIs can provide long-term treatment and control of a chronic skin disease that may persist for years.

Administration, Topical↗
PubMed2003

Atopic eczema. What has caused the epidemic in industrialised countries and can early intervention modify the natural history of atopic eczema?

Atopic eczema (AE) has a lifetime prevalence of between 15 and 20% in industrialized countries, but a very low prevalence in rural Africa. The 'atopic eczema epidemic' has developed in industrialized countries within the last four decades. The disease has a strong genetic influence, so environmental factors must be responsible for the dramatic increase in disease prevalence. It is therefore fair to consider what interventions may change its prevalence. In this article, several factors are considered: the increased number of doctors in industrialized countries, the development of drugs like topical steroids and emollients, the 'demanding parents' and 'old mother' syndromes, introduction of vaccination programmes, allergen exposure, breastfeeding and the possible beneficial effects of probiotics. In 90% of children with AE, onset is before the age of 5. Its course runs over years. Approximately two out of three outgrow the disease between 7 and 12 years of age. Although its cause is unknown, type I allergic reactions are common and allergen avoidance has been attempted in many studies as a preventive measure in atopic dermatitis. However, results are rather disappointing. The use of probiotics, i.e. daily intake of Lactobacillus, has proven effective in preventing, or at least delaying, the development of atopic eczema. So has breastfeeding, although some studies cannot confirm its beneficial effect. Therapeutic interventions using antihistamines, desensitisation and control of skin inflammation using topical steroids have not proven successful in shortening the course of atopic eczema, although controlled studies are lacking. The use of emollients has, however, a documented effect in up to one of three children with mild atopic eczema. It will be interesting to observe if the new topical immuno-modulators, tacrolimus and pimecrolimus, may be able to shorten the natural course of the disease.

Journal Article↗
PubMed2002

Treatment principles of atopic dermatitis.

UNLABELLED: Atopic dermatitis (AD) is today the most common, chronic inflammatory skin disease among children in developed countries. Its cumulative prevalence varies from 20% in northern Europe and the USA to approximately 5% in Mediterranean countries. As a chronic disease it puts a special demand on treatment. There is no curative therapy, but competent guidance on treatment principles can control the disease in most, if not all children. This article summarizes the evidence-based knowledge that relates to the treatment of atopic eczema. It also gives advice and opinions on prophylactic measures as these are the focus of interest from most parents. LEARNING OBJECTIVE: This article should enable you to give advice and guidance to parents of children with AD, including what is necessary for diagnosis, what is of value and importance considering allergies and allergological investigations, allergen exposure, prophylactic measures, diets and indoor environment. Finally, you should be able to explain the diversity of treatment principles for parents.

Allergens↗
PubMed2001

Association between atopic dermatitis and insulin-dependent diabetes mellitus: a case-control study.

BACKGROUND: Up to two-thirds of children with atopic dermatitis have IgE-mediated allergic reactions and a Th2 immune reactivity pattern with low production of interferon gamma and high production of interleukin 4 after allergen stimulation of T lymphocytes. Insulin-dependent diabetes mellitus (IDDM) seems to be associated with a Th1 immune reactivity pattern. We therefore postulated that these diseases may be inversely associated. METHODS: We designed a case-control study including 920 children with IDDM, registered in the Danish Registry for Childhood Diabetes, and a sample of 9732 non-diabetic children registered in the Danish Medical Birth Registry. The children were aged 3-15 years. Information on atopic dermatitis was obtained by questionnaires. FINDINGS: The cumulative incidence of atopic dermatitis up to age 15 years was 13.1% among children with IDDM and 19.8% in non-diabetic children (p<0.0001). Among children who developed IDDM, the incidence of atopic dermatitis was significantly lower than in the controls before onset of IDDM (73 cases in 5314 person-months vs 1375 in 57432 person-months; odds ratio 0.49 [0.39-0.63]). After onset of IDDM, diabetic and non-diabetic groups did not differ in incidence of atopic dermatitis (1.36 [0.89-2.07]). INTERPRETATION: Our findings may be explained by different acquired or inherited reactivity patterns associated with atopic dermatitis (Th2) and IDDM (Th1). The results do not allow us to find out whether early development of atopic dermatitis reduces the risk of IDDM, or a propensity for IDDM reduces the risk of early-onset atopic dermatitis.

Adolescent↗
PubMed2001

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Adolescent↗
PubMed2001

CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease expressed early in life. Disease development is primarily determined by as yet unknown genetic factors, leading to the accumulation of activated T lymphocytes in the skin. OBJECTIVES: To investigate the nature of these T cells. METHODS: T-cell lines could be established from AD skin biopsies, but not from normal skin or AD peripheral blood, when placed in RPMI 1640 medium with 10% human AB serum, antibiotics, and the T-lymphocyte growth factors interleukins 2 and 4. The cell lines were subjected to phenotypic analysis using a fluorescence-activated cell sorter and compared with lymphocytes from AD and normal control peripheral blood. RESULTS: T-cell lines from 22 of 24 consecutive skin biopsies taken from 24 adult patients with AD were established. All cells were T lymphocytes expressing several activation markers. A significant proportion of the lymphocytes had stable expression of a CD4+ CD8+ phenotype (26% +/- 6%; mean +/- SEM). Such double-positive T lymphocytes are normally only seen in the thymus and not in the peripheral immune system. CD4+ CD8+ cells in peripheral blood of the patients (12.5% +/- 3.3%) were also detected. CONCLUSIONS: We suggest that a basic pathophysiological change in AD may be a faulty maturation of the T-lymphocyte system, leading to skin inflammation with CD4+ CD8+ T lymphocytes resembling immature T cells. This is likely to lead to skewing of many immune reactions in the patients.

Adolescent↗
PubMed2001

Expression of IL-18 mRNA and secretion of IL-18 are reduced in monocytes from patients with atopic dermatitis.

BACKGROUND: IL-18 has been found to be an IFN-gamma-inducing factor that plays an important role in T(H)1 cell activation. Recently, IL-18 has also been found to enhance a T(H)2 cellular response in a specific setting. OBJECTIVE: The aim of this study was to elucidate the role of monocytes and soluble factors, with special focus on IL-18, in the pathogenesis of atopic dermatitis (AD). METHODS: The release of cytokines from PBMCs and purified monocytes was measured through use of ELISA; mRNA expression was evaluated by RT-PCR. The results from patients with AD were compared with those from healthy controls. RESULTS: IL-18 secretion was reduced in both unstimulated and lipopolysaccharide-stimulated monocytes from patients with AD. The mRNA expression of IL-18 and IL-1 beta-converting enzyme was significantly reduced in unstimulated monocytes from patients with AD (P <.03 and P <.01, respectively). Patients with AD had an elevated secretion of prostaglandin E(2) (PGE(2)) from unstimulated PBMCs (P <.001). The anti-PGE(2) antibody reversed the suppressive effect of PGE(2) on IL-18 secretion in unstimulated PBMCs from patients with AD. CONCLUSIONS: Decreased IL-18 production, together with a significantly reduced IL-18 and ICE mRNA expression in unstimulated monocytes and elevated PGE(2) secretion from PBMCs, was associated with the pathogenesis of AD.

Adolescent↗
PubMed2000

Telomerase activity is increased and telomere length shortened in T cells from blood of patients with atopic dermatitis and psoriasis.

We studied telomerase activity and telomere length in PBMC and purified CD4(+) and CD8(+) T cells from blood obtained from a total of 32 patients with atopic dermatitis, 16 patients with psoriasis, and 30 normal controls. The telomerase activity was significantly increased in PBMC from the patients compared with PBMC from normal donors. This increase was most pronounced in the subpopulation of CD4(+) T cells, which were significantly above the activity of the CD8(+) T cells in atopic dermatitis, psoriasis patients, and control persons. The telomere length was significantly reduced in all T cell subsets from both atopic dermatitis and psoriasis patients compared with normal individuals. Furthermore, the telomere length was found to be significantly shorter in CD4(+) memory T cells compared with the CD4(+) naive T cells, and both of the cell subsets from diseases were shown to be of significantly shorter telomere length than the same cell subsets from normal controls. No significant difference was observed between CD8(+)CD28(-) and CD8(+)CD28(+) T cell populations in both diseases. However, the telomere length of CD8(+)CD28(+) T cells from both diseases was significantly shorter than CD8(+)CD28(+) T cell subsets from normal donors. In conclusion, the increased telomerase activity and shortened telomere length indicates that T lymphocytes in atopic dermatitis and psoriasis are chronically stimulated and have an increased cellular turnover in vivo.

Adolescent↗
PubMed2000

Treatment of psoriasis with oral liarozole: a dose-ranging study.

BACKGROUND: Liarozole is an inhibitor of the metabolism of all-trans-retinoic acid. Systemic administration increases tissue levels of this endogenous retinoid and has been reported to improve psoriasis in an open, uncontrolled study. OBJECTIVES: A multicentre, double-blind, placebo-controlled, dose-ranging study was therefore undertaken to determine the lowest effective oral dose of liarozole in the treatment of psoriasis vulgaris. PATIENTS/METHODS: Adult male and postmenopausal female patients requiring systemic treatment for psoriasis were randomized to receive placebo or liarozole at total daily doses of 50 mg, 75 mg or 150 mg for 12 weeks. The daily doses were each divided into two equal (morning and evening) doses. Response was assessed using an eight-point global scale to assess improvement and by monitoring the Psoriasis Area and Severity Index (PASI). The primary end-point was the proportion of subjects in each treatment group demonstrating 'marked improvement' or better as assessed on the eight-point scale. The tolerability of the treatment was assessed by recording mucocutaneous effects of retinoids and all adverse events. Biochemical and haematological monitoring were also performed. RESULTS: One hundred and thirty-nine subjects were randomized (118 male and 21 female) and 116 completed the study. A marked improvement or better response was observed in 6% of subjects on placebo, 18% on liarozole 50 mg, 11% on 75 mg and 38% on 150 mg. Only in the 150-mg group was the response rate significantly different to placebo (P < 0.001). Over the treatment period the mean PASI changed from 15.9 to 15.4 on placebo, from 17.4 to 13.8 on liarozole 50 mg, from 17.5 to 14.5 on 75 mg and from 15.8 to 8.8 on 150 mg. Again, only in the group receiving 150 mg was the response significantly better than placebo (P < 0.001). Liarozole was generally well tolerated. Mucocutaneous retinoid effects were generally infrequent and mild. Five subjects were withdrawn from treatment as a result of adverse events that may have been treatment related. These events were abnormalities of liver enzymes in two cases, an episode of erythema multiforme (in a patient receiving placebo), an allergic reaction in one and a rash accompanied by deterioration of the psoriasis in another. There was mild elevation of triglycerides in the groups receiving liarozole 75 mg and 150 mg daily. In males, the serum luteinizing hormone and testosterone levels rose significantly in all the active treatment groups. CONCLUSIONS: The data confirm that liarozole is an effective treatment for psoriasis and indicate that the lowest effective dose is 75 mg twice daily. The drug seems generally to be well tolerated.

Administration, Oral↗
PubMed2000

Clinical aspects of atopic dermatitis.

Atopic dermatitis (AD), or atopic eczema, is the most common, chronic inflammatory disease among children in industrialized countries. We still lack knowledge of its pathophysiology and in particular the role of allergy as both an eliciting factor for disease expression and for disease activity. This article describes the clinical symptoms of the disease and its qualitatively different aspects. AD cannot be understood as being induced by one factor only, e.g. allergy, and this is important when planning treatment strategies. It is also important to realize the very wide range of disease intensity: from subclinical, or latent AD, in which only a few symptoms are present and thus which prevents a clear diagnosis of AD, to its most severe forms including erythroderma. It's unknown aetiology, the wide range in symptomatology, and the fluctuating course (including the many eliciting factors) form the background for our diagnostic and therapeutic difficulties of atopic eczema. AD is prevalent in childhood, but the atopic trait continues, not only for later respiratory allergies, but also for skin diseases in adulthood (such as AD itself or the frequent irritant contact dermatitis of the hands). A child with an acute and first attack of AD is therefore a challenge to the child, its parents and - certainly - to the doctor. However, after stressing the chronicity of the disease, it is equally important to assure the parents that this disease is, in most cases, controllable through correct treatment and that it has a good prognosis: It is not a 'life sentence', but a controllable disease in an otherwise healthy child.

Adult↗
PubMed2000

Paraneoplastic skin manifestations of lung cancer.

Two cases are reported illustrating a parallel course of extensive skin manifestations and lung cancer. The cases presented features of paraneoplastic acrokeratosis (Bazex's syndrome) and erythema gyratum repens though they did not completely correspond to these well-defined conditions. In both cases the cutaneous eruption appeared more than a year prior to the diagnosis of lung cancer, and the skin disease resolved completely within half a year following surgical removal of the cancer. The need is stressed for repeated cancer screens when a cutaneous marker of internal malignancy is suspected.

Female↗
PubMed1999

Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma.

BACKGROUND: Telomeres shorten with successive cell divisions in normal somatic cells. Telomerase is a ribonucleoprotein enzyme associated with cellular proliferation and plays an important role in maintaining the stability of chromosomes and the length of DNA telomeres. Telomerase activity has been detected in tissues from many human tumors, but is not present in the majority of normal tissues. Thus, measurement of telomerase activity and telomere length may contribute to understanding the mechanism of tumorigenesis and provide useful diagnostic or prognostic information. The aim of this study was to investigate the telomerase activity and telomere length from patients with cutaneous T-cell lymphoma (CTCL). METHODS: Eighteen skin-homing T-cell lines were established from skin biopsies and 10 peripheral blood mononuclear cells (PBMC) were isolated from patients with various stages of CTCL together with 22 PBMC from healthy donors. For each sample an identical amount of cellular protein was measured quantitatively for telomerase activity using the telomerase polymerase chain reaction-enzyme-linked immunosorbent assay based on the telomeric repeat amplification protocol method. Telomere length was assayed using a commercial kit. RESULTS: Eight of ten PBMC and 16 of 18 skin-homing T-cell lines from patients with CTCL showed moderate to strong telomerase activity. Freshly obtained PBMC from healthy donors showed weak levels of telomerase activity. A shorter telomere length was found in cell lines and PBMC from patients with CTCL compared with healthy controls. Four skin-homing T-cell lines going into growth crisis showed sharply reduced telomerase activity. CONCLUSIONS: The results of the current study indicate that both skin-homing T-cells and PBMC from CTCL have high telomerase activity and short telomere length. These changes are similar to the changes observed in the majority of malignant cells including other types of T-cell lymphoma. It is interesting to note that even in the very early stages of CTCL such as parapsoriasis (which is a clinically benign disease) the changes already are present, indicating that a significantly high level of telomerase activity frequently occurs in CTCL and may be an important event in tumorigenesis. Telomerase activity and telomere length are useful markers for CTCL risk assessment.

Aged↗