Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.

Background: The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis.

Objective: The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here.

A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris.

Background: The calcipotriol/betamethasone dipropionate two-compound product Dovobet/Daivobet/Taclonex(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time.

Objectives: To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis.

Inverse regulation of the nuclear factor-kappaB binding to the p53 and interleukin-8 kappaB response elements in lesional psoriatic skin.

Nuclear factor-kappaB (NF-kappaB) is an inducible nuclear transcription factor regulating a range of cellular processes. An imbalance of the DNA binding activity of NF-kappaB may, therefore, be part of the pathophysiological mechanisms in psoriasis. The purpose of this study was to determine the NF-kappaB DNA binding activity in psoriatic skin using three different kappaB sites and to determine how DNA binding activity was modulated by the anti-psoriatic drug calcipotriol.

Lysophosphatidylcholine induces keratinocyte differentiation and upregulation of AP-1- and NF-kappaB DNA-binding activity.

Lysophosphatidylcholine (lysoPC) is generated by the action of phospholipase A2 on membrane phosphatidylcholine, the most abundant cellular phospholipid. In vitro, lysoPC has pro-inflammatory properties, as it upregulates the expression of adhesion molecules and is a chemoattractant to monocytes and T lymphocytes. It upregulates the expression of a variety of genes including genes encoding growth factors and cyclooxygenase-2 and modulates other cellular responses like proliferation and differentiation.

The mitogen-activated protein kinases p38 and ERK1/2 are increased in lesional psoriatic skin.

Background: Alterations in specific signal transduction pathways may explain the hyperproliferation and abnormal differentiation of the keratinocytes as well as the increased expression of inflammatory cytokines seen in psoriasis. Major signalling pathways used by eukaryotic cells to transduce extracellular signals into cellular responses impinge on the mitogen-activated protein kinases (MAPKs).

Objectives: To investigate the expression of the MAPK p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in psoriatic skin.

Activator protein 1 DNA binding activity is decreased in lesional psoriatic skin compared with nonlesional psoriatic skin.

Background: Psoriasis is a common benign skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. The transcription factor activator protein 1 (AP-1) is known to play an important role in cell proliferation and differentiation.

Objectives: To investigate AP-1 DNA binding activity in psoriatic skin.

Expression of the T-helper 2-specific chemokine receptor CCR4 on CCR10-positive lymphocytes in atopic dermatitis skin but not in psoriasis skin.

Background: Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases. AD is generally perceived as a T-helper (Th) 2-dominated disease whereas psoriasis is a Th1-dominated disease. The chemokine cutaneous T-cell attracting chemokine (CTACK) and its receptor CCR10 attract skin-homing lymphocytes to inflamed skin, suggesting that CCR10+ cells in AD and psoriasis should be of Th2 and Th1 type, respectively.

1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes.

1alpha,25-Dihydroxyvitamin D3 added to human keratinocytes increases differentiation through an activation of the transcription factor activator protein 1. We have previously reported that the 1alpha,25-dihydroxyvitamin D3-induced increase of activator protein 1 DNA binding activity is mediated by a protein kinase C-independent mechanism. The purpose of this study was to investigate further the mechanisms by which 1alpha,25-dihydroxyvitamin D3 modulates activator protein 1 DNA binding activity in cultured normal human keratinocytes.

Vitamin D and UVB radiation therapy.

Several studies have examined the combination of calcipotriene and UVB radiation in the treatment of psoriasis. Most show greater clearing with the combination than with monotherapy with either treatment. Data from one study found that calcipotriene had a UVB-sparing effect when combined with broadband UVB phototherapy, resulting in fewer UVB exposures and a lower cumulative dose.

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.

[Allergic contact eczema because of diethylthiourea in neoprene rubber].

Three cases are reported of acute allergic contact dermatitis caused by diethylthiourea in the neoprene rubber used in a diving suit and orthopedic braces. Patch testing should be done with the specific thiourea compounds, because testing with material from the suspected products may be negative. Cross-reactivity between thiourea compounds is uncommon.

Treatment of hyperkeratotic dermatitis of the palms (eczema keratoticum) with oral acitretin. A single-blind placebo-controlled study.

Hyperkeratotic dermatitis of the palms--also called eczema keratoticum--is a chronic, sometimes disabling condition in middle-aged persons. We carried out a single-blind, placebo-controlled study using acitretin in 29 patients. Fourteen patients received active therapy (30mg acitretin daily) and 15 placebo.

Expression and function of CD43 and CDw60 on T cells from patients with atopic dermatitis.

Signalling via the CD43 and CDw60 epitopes has been reported as providing two novel pathways of T-lymphocyte activation. In Wiskott-Aldrich syndrome, which has atopic eczema-like skin symptoms, there is a defective expression of CD43, while CDw60 is strongly expressed on T cells from rheumatoid arthritis synovial fluid and from psoriatic skin lesions, and on blood mononuclear cells from patients with cutaneous T-cell lymphoma. We therefore studied the expression and function of these phenotypes on peripheral blood mononuclear cells and on CD4+ and CD8+ T-cell subsets from patients with atopic dermatitis.

The insufficient suppression of viral load by saquinavir hard gel is reversible: a retrospective cohort study.

Purpose: To assess the effect of changing antiretroviral therapy in patients initially treated with saquinavir hard gel capsule (hgc).

Method: A retrospective cohort study comparing the virological and immunological responses in antiretroviral-naïve patients initially treated with a regimen of saquinavir-hgc, zidovudine, and lamivudine, with patients receiving either ritonavir or indinavir on a background of zidovudine and lamivudine.

Results: Twenty-nine patients starting with saquinavir-hgc as the protease inhibitor (PI) component were compared to 58 patients starting with ritonavir (n = 16) or indinavir (n = 42).

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).

Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis.

We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control.

Herpesvirus type 1-8 in BAL fluid from HIV-1-infected patients with suspected pneumonia and from healthy individuals.

Pneumonia is still a major problem in human immunodeficiency virus (HIV)-infected patients, and despite extensive investigation the aetiology remains unknown in many cases. The prevalence of the eight human herpesviruses was determined by polymerase chain reaction in 91 samples of bronchoalveolar lavage (BAL) fluid from 72 HIV-infected patients with 91 episodes of suspected pneumonia. The presence of herpesviruses was related to clinical and immunological findings and the prevalence of herpesviruses in HIV-infected patients was compared with the prevalence in BAL fluid from 50 healthy, immunocompetent individuals.

Herpesvirus type 1-8 in sinus aspirates from HIV-infected patients and immunocompetent individuals.

Sinusitis is frequently occurring in HIV-infected patients, but in a substantial number of cases the etiology is unknown. The purpose of this study was by PCR 1) to determine the prevalence of the eight human herpesviruses in sinus aspirates from 24 HIV-positive/AIDS patients with sinusitis 2) to relate the presence of herpesvirus DNA to clinical and immunological parameters and 3) to compare the prevalence of herpesvirus DNA in sinus aspirates from HIV-infected patients with the prevalence observed in 50 immunocompetent patients with sinusitis. DNA from HSV-1, EBV, CMV and HHV-8 was detected in 8 (33%) of the sinus aspirates from HIV-infected patients.

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.

Cytokine expression of skin T-lymphocytes from patients with atopic dermatitis.

We analysed the cytokine profile of skin T cells by establishing 11 T-cell lines from adult patients with moderate-to-severe atopic eczema using T-cell growth factors interleukin-2 and interleukin-4. We compared T-cell lines from lesional skin of atopic dermatitis patients with those from non-atopic skin of patients with other skin diseases, observing that T-cell lines of patients with atopic dermatitis unstimulated cultures expressed a Th1 profile. After stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, the cytokine expression showed rapid initial upregulation of Th2 followed by a Th1 profile.

The effect of nevirapine in combination with nelfinavir in heavily pretreated HIV-1-infected patients: a prospective, open-label, controlled, randomized study.

The purpose of the current study was to determine the efficacy and safety of nevirapine combined with nelfinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) in patients previously exposed to highly active antiretroviral therapy (HAART). In a prospective, open-label, randomized study, 56 HIV-infected adults who had received HAART, including saquinavir hard gel capsule, ritonavir, or indinavir, were randomly assigned to receive nevirapine in addition to nelfinavir and two NRTIs. The proportion of patients who achieved an undetectable viral load (plasma HIV-RNA <200 copies/ml) at weeks 24 and 36 was significantly higher in the nevirapine group than in the control group (55% and 52% vs.

Hair reduction using a new intense pulsed light irradiator and a normal mode ruby laser.

Objective: The main purpose of this clinical study was to compare the effectiveness of an intense pulsed light irradiator system (IPL) and a normal mode ruby laser for hair removal.

Materials And Methods: Thirty-one patients were treated 3 times with a new IPL system on one side of the chin and neck and with a normal mode ruby laser on the other side. After 6 months, nine of the patients received 3 additional IPL treatments and 11 patients received 3 additional ruby laser treatments.

De novo identification of cell-type specific antibody-antigen pairs by phage display subtraction. Isolation of a human single chain antibody fragment against human keratin 14.

The aim of this study was to identify novel antibodies directed against cytosolic keratinocyte-specific antigens from a phage display antibody repertoire by using phage display subtraction. Phage display is a method of displaying foreign molecules on the surface of filamentous bacteriophage particles. It allows the interaction between two cognate molecules to be analysed through affinity selections.

Intense pulsed light source for treatment of small melanocytic nevi and solar lentigines.

Objective: The purpose of this clinical study was to evaluate the effectiveness of an intense pulsed light (IPL) irradiator system for the treatment of benign pigmented lesions.

Materials And Methods: A total of 18 patients with lentigo solaris and eight patients with melanocytic nevi were treated once with an IPL system. After 2 months, the effect was evaluated on close-up photographs.