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1.
Br J Dermatol ; 180(4): 836-848, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30171686

RESUMO

BACKGROUND: Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose-induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes. OBJECTIVES: To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys-d-Pro-Thr (KdPT), a tripeptide derived from α-melanocyte-stimulating-hormone, has protective effects. METHODS: We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model. RESULTS: HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG-induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures. CONCLUSIONS: Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.


Assuntos
Pé Diabético/prevenção & controle , Epiderme/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Glicemia/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Pé Diabético/sangue , Pé Diabético/etiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Epiderme/fisiologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/ultraestrutura , Microscopia de Força Atômica , Oligopeptídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
J Eur Acad Dermatol Venereol ; 33(12): 2371-2379, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442331

RESUMO

BACKGROUND: Aprepitant is a neurokinin 1 receptor (NK1R) antagonist used for its antipruritic properties in dermatoses and systemic diseases. The mode of action is still unclear. A peripheral effect is assumed as aprepitant shows efficacy in inflammatory skin diseases including prurigo nodularis (PN). OBJECTIVES: To investigate the peripheral effects of NK1R antagonism in PN and cell culture models. METHODS: Subjects with PN received an aprepitant treatment. Clinical, morphological and immunohistochemical changes were investigated in skin biopsies before and after treatment. Expression of NK1R was analysed by immunohistochemistry and for downstream pathways ((p)ERK1/2) by Western blotting in PN patients and matched healthy volunteers. Effects of NK1R blocking were analysed in cell cultures of primary keratinocytes by Western blotting for (p)ERK1/2 and by qPCR for NK1R, interleukin (IL)-1beta, IL-6, IL-8 and TNFalpha. RESULTS: Aprepitant treatment showed significant reduction in pruritus intensity (P < 0.05) in PN and relevant immunohistochemical changes (down: CD5, CD25, up: CD79a, IL4). NK1R expression was higher in keratinocytes of PN patients compared to healthy controls. After treatment, epidermal NK1R expression increased while expression and activation of ERK1/2 decreased. In vitro, receptor up-regulation and reduced expression and activation of ERK1/2 were confirmed and reduced IL-expression shown when blocking NK1R. CONCLUSION: Our data confirm that NK1R antagonists such as aprepitant exhibit effects in the skin. Epidermal receptor expression, epidermal inflammatory ILs, ERK1/2 MAPK signalling and cutaneous inflammatory infiltrate were targets of NK1R antagonism. This may explain partly the antipruritic effect of NK1R antagonists next to its role in the central nervous system.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Prurigo/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico
3.
Br J Dermatol ; 178(2): 406-414, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28845523

RESUMO

BACKGROUND: Dupilumab, a human anti-interleukin-4 receptor alpha monoclonal antibody, significantly improved clinical signs and symptoms in adults with moderate-to-severe atopic dermatitis in a randomized, double-blind, placebo-controlled, phase IIa trial. OBJECTIVES: We evaluate health-related quality of life (HRQoL) and correlation of HRQoL with secondary clinical and patient-reported outcomes in a subset of patients from this trial of dupilumab. METHODS: Patients were randomized to 300 mg weekly subcutaneous dupilumab or placebo for 12 weeks (trial registration: NCT01548404). The Quality of Life Index of Atopic Dermatitis (QoLIAD) score (exploratory outcome) and its correlation with efficacy outcomes [Eczema Area and Severity Index (EASI); primary end point; SCORing Atopic Dermatitis (SCORAD), SCORAD visual analogue scale (VAS) scores for sleep and pruritus, pruritus numerical rating scale (NRS) and 5-dimensional pruritus] were assessed in 64 adults with moderate-to-severe atopic dermatitis. RESULTS: Mean QoLIAD scores at baseline ± standard error (SE) were 13·3 ± 1·34 and 11·3 ± 1·09 for the placebo and dupilumab groups, respectively. Dupilumab significantly improved QoLIAD score after 12 weeks of treatment vs. placebo (mean % change from baseline in QoLIAD score ± SE: -64·0 ± 6·91 vs. -11·1 ± 9·31). Least squares mean % difference from baseline vs. placebo in QoLIAD score ±SE was -52·0 ± 11·43, P < 0·001). QoLIAD scores significantly correlated with changes in efficacy outcomes, including EASI (r = 0·44), 5-dimensional pruritus (r = 0·49), pruritus NRS (r = 0·41), total SCORAD (r = 0·56) and SCORAD VAS scores for sleep (r = 0·47) and pruritus (r = 0·54); all P < 0·05. CONCLUSIONS: Dupilumab improved QoLIAD scores in adults with atopic dermatitis and was significantly associated with improvements in study outcomes.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Qualidade de Vida , Adulto , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Resultado do Tratamento
4.
Clin Exp Allergy ; 46(8): 1066-74, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27196703

RESUMO

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.


Assuntos
Receptor Tipo 1 de Melanocortina/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Adulto , Alérgenos/imunologia , Animais , Basófilos/imunologia , Basófilos/metabolismo , Biópsia , Quimiotaxia/imunologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Imunoglobulina E/imunologia , Masculino , Camundongos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Testes de Provocação Nasal , Diester Fosfórico Hidrolases/metabolismo , Pólen/imunologia , Pirofosfatases/metabolismo , Receptor Tipo 1 de Melanocortina/genética , Testes de Função Respiratória , Rinite Alérgica/diagnóstico , Rinite Alérgica/genética , Testes Cutâneos , Adulto Jovem , alfa-MSH/metabolismo
5.
J Dtsch Dermatol Ges ; 14 Suppl 6: 29-37, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869374

RESUMO

Based on numerous trials, oral tetracyclines and most commonly their second-generation derivative doxycycline have become the main pillar in systemic rosacea treatment. However, the only preparation that has been approved so far in this setting is 40 mg doxycycline in an anti-inflammatory dosage and with a modified release formulation. With the introduction of this once-daily, non-antibiotic dosing of doxycycline, oral therapy is more commonly prescribed as first-line treatment in moderate to severe papulopustular rosacea. In addition, topical and oral strategies are often used in combination due to the more substantial improvements compared to monotherapy. Although several other non-approved oral agents like macrolides, isotretinoin, and carvedilol have been evaluated for systemic treatment and showed promising results, yet the experience with these drugs in rosacea is limited, and thus they should be reserved for special situations.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Administração Cutânea , Administração Tópica , Fármacos Dermatológicos/administração & dosagem , Medicina Baseada em Evidências , Alemanha , Humanos , Assistência Centrada no Paciente/métodos , Avaliação de Sintomas/métodos , Resultado do Tratamento
6.
J Dtsch Dermatol Ges ; 14 Suppl 6: 29-37, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869375

RESUMO

Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler der systemischen Rosazea-Therapie. Bisher ist dafür jedoch nur Doxycyclin 40 mg in antientzündlicher Dosierung mit veränderter Wirkstofffreisetzung zugelassen. Seit Einführung der Therapie mit Doxycyclin einmal täglich in nicht antibiotischer Dosierung wird die orale Therapie häufiger als Erstbehandlung bei mittelschwerer bis schwerer papulopustulöser Rosazea verschrieben. Oft wird diese Behandlung aufgrund der besseren Wirksamkeit im Vergleich zur Monotherapie auch mit einer topischen Behandlung kombiniert. Obwohl in der Systemtherapie weitere, nicht zugelassene Wirkstoffe wie Makrolide, Isotretinoin und Carvedilol mit viel versprechenden Ergebnissen untersucht wurden, ist die vorliegende Erfahrung bisher begrenzt, so dass diese Substanzen speziellen Situationen vorbehalten bleiben sollten.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Administração Cutânea , Administração Tópica , Fármacos Dermatológicos/administração & dosagem , Medicina Baseada em Evidências , Alemanha , Humanos , Assistência Centrada no Paciente/métodos , Avaliação de Sintomas/métodos , Resultado do Tratamento
7.
J Dtsch Dermatol Ges ; 14 Suppl 6: 4-15, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869372

RESUMO

Rosacea is a common chronic inflammatory skin disorder that typically occurs in adults and affects the face. Synonyms of rosacea include "acne rosacea", "couperose" and "facial erythrosis", in German also "Kupferfinne" and "Rotfinne". The disorder is characterised by a chronic and flaring course and is caused by a genetically predisposed, multifactorial process. A higher incidence is seen in people with fair skin and a positive family history. The characteristic rosacea symptoms manifest primarily, but not exclusively centrofacially, with forehead, nose, chin and cheeks significantly affected. Based on the various main symptoms a classification of the individual clinical pictures can be performed. However, a classification often does not reflect the clinical reality, since the various symptoms commonly coexist. The present review provides an introduction on pathogenesis and clinical manifestations of rosacea and prefers a symptom-oriented therapy approach.


Assuntos
Dermatoses Faciais/diagnóstico , Dermatoses Faciais/terapia , Assistência Centrada no Paciente/métodos , Rosácea/diagnóstico , Rosácea/terapia , Avaliação de Sintomas/métodos , Medicina Baseada em Evidências , Dermatoses Faciais/genética , Alemanha , Humanos , Rosácea/genética , Resultado do Tratamento
8.
J Dtsch Dermatol Ges ; 14 Suppl 6: 17-28, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869373

RESUMO

Obwohl bislang für die Rosazea keine kurative Therapie besteht, können verschiedene Optionen zur Behandlung der Symptome und zur Vorbeugung von Exazerbationen empfohlen werden. Neben Selbsthilfemaßnahme wie der Vermeidung von Triggerfaktoren und einer geeigneten Hautpflege sollte das Rosazea-Management bei Patienten mit erythematöser und leichter bis schwerer papulopustulöser Rosazea die Anwendung topischer Präparate als First-Line-Therapie umfassen. Da Überlappungen der charakteristischen Rosazea-Symptome im klinischen Alltag die Regel sind, sollte die medikamentöse Therapie auf die individuellen Symptome zugeschnitten werden; auch eine Kombinationstherapie kann erforderlich sein. Zu den für die Behandlung der Hauptsymptome der Rosazea zugelassenen Wirkstoffen gehören Brimonidin gegen das Erythem sowie Ivermectin, Metronidazol oder Azelainsäure gegen entzündliche Läsionen. Ihre Wirksamkeit wurde in zahlreichen validen, gut kontrollierten Studien belegt. Darüber hinaus existieren verschiedene nicht zugelassene topische Behandlungsmöglichkeiten, deren Wirksamkeit und Sicherheit noch in größeren, kontrollierten Studien zu untersuchen ist.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Administração Cutânea , Administração Tópica , Fármacos Dermatológicos/administração & dosagem , Medicina Baseada em Evidências , Alemanha , Humanos , Assistência Centrada no Paciente/métodos , Avaliação de Sintomas/métodos , Resultado do Tratamento
9.
J Dtsch Dermatol Ges ; 14 Suppl 6: 4-16, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869378

RESUMO

Rosazea ist eine häufige chronisch-entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind. Dabei werden unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine Klassifizierung wird oftmals jedoch nicht der klinischen Realität gerecht, da die verschiedenen Symptome häufig gemeinsam auftreten. Diese Übersichtarbeit führt in die Pathogenese und Klinik der Rosazea ein und plädiert für einen symptomorientierten Therapieansatz.


Assuntos
Dermatoses Faciais/diagnóstico , Dermatoses Faciais/terapia , Assistência Centrada no Paciente/métodos , Rosácea/diagnóstico , Rosácea/terapia , Avaliação de Sintomas/métodos , Medicina Baseada em Evidências , Dermatoses Faciais/genética , Alemanha , Humanos , Rosácea/genética , Resultado do Tratamento
10.
J Dtsch Dermatol Ges ; 14 Suppl 6: 17-27, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27869379

RESUMO

Although there is presently no cure for rosacea, there are several recommended treatment options available to control many of the symptoms and to prevent them from getting worse. In addition to self-help measures like avoidance of trigger factors and proper skin care, rosacea management should include topical medications as one of the first-line choices for patients with erythematous and mild to severe papulopustular rosacea. Since mixed forms of characteristic rosacea symptoms are more common, medical treatment must be symptom-tailored for each individual case and will often involve a combination therapy. Approved topical agents for the major symptoms of rosacea encompass brimonidine for erythema and ivermectin, metronidazole or azelaic acid for inflammatory lesions, all of which have shown their efficacy in numerous valid, well-controlled trials. In addition, there are several other, not approved topical treatments which are possible options that require further validation in larger well-controlled studies.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Administração Cutânea , Administração Tópica , Fármacos Dermatológicos/administração & dosagem , Medicina Baseada em Evidências , Alemanha , Humanos , Assistência Centrada no Paciente/métodos , Avaliação de Sintomas/métodos , Resultado do Tratamento
11.
J Eur Acad Dermatol Venereol ; 29(7): 1406-14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25917315

RESUMO

BACKGROUND: Accurate and reliable assessment of changes in psoriasis severity is critical in clinical trials of therapies. OBJECTIVE: To compare Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), and the Lattice System Physician's Global Assessment (LS-PGA) in a trial of systemic treatments for plaque psoriasis vulgaris and to assess whether they measure change in psoriasis induced by therapy. METHODS: Patients were randomized to voclosporin or cyclosporine for 24 weeks (the '24-week-treatment' group, n = 366), or placebo for 12 weeks followed by voclosporin for 12 weeks (the 'initial-placebo' group, n = 89). RESULTS: All scoring systems changed in concert and were sensitive enough to detect reductions in severity during placebo therapy as well as with active therapy (P < 0.01 for each measurement). At study onset, there were poorer correlations of sPGA with PASI (r = 0.45) and LS-PGA (r = 0.39) than between PASI and LS-PGA (r = 0.68). After therapy, all correlations were stronger, but sPGA continued to be less well correlated (with PASI, r = 0.85; with LS-PGA, r = 0.79) than LS-PGA with PASI (r = 0.90). Two- or three-step improvements in LS-PGA showed very good to excellent accuracy in corresponding to PASI-50 and PASI-75, respectively, and were more accurate than comparable changes in sPGA. CONCLUSION: PASI, sPGA and LS-PGA are responsive to the varying degrees of improvement in psoriasis induced by either placebo or active therapy. While the three systems capture similar information, each has different reasons for use in a clinical trial.


Assuntos
Competência Clínica , Ciclosporina/uso terapêutico , Médicos/normas , Psoríase/diagnóstico , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
12.
J Eur Acad Dermatol Venereol ; 29(7): 1415-20, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25917214

RESUMO

BACKGROUND: Systems for determining psoriasis severity in clinical trials have not been sufficiently validated against patients' perceived quality of life. OBJECTIVE: To validate three systems of physician-determined psoriasis severity (the Lattice System Physician's Global Assessment [LS-PGA], Psoriasis Area and Severity Index [PASI] and static Physician's Global Assessment [sPGA]). METHODS: Data were from a 24-week randomized, double-blind, placebo-controlled, multicenter trial of therapy with oral calcineurin inhibitors in 445 patients. Construct validity was measured by correlations of the three severity scores with patients' self-reported quality of life (QoL) from the Dermatology Life Quality Index (DLQI) and a DLQI item about psoriasis symptoms. RESULTS: All severity systems were moderately and positively correlated with QoL, indicating construct validity. QoL was most consistently related to physicians' assessments of body surface area involved with psoriasis (iBSA) followed by, in the order of consistency, plaque elevation, erythema and scale. CONCLUSIONS: The LS-PGA weights iBSA and aspects of plaque morphology in concert with their relative effects on QoL. The LS-PGA, sPGA and PASI are validated by their relationship to QoL in a clinical trial.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Competência Clínica , Ciclosporina/administração & dosagem , Médicos/normas , Psoríase/tratamento farmacológico , Qualidade de Vida , Administração Oral , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Psoríase/diagnóstico , Psoríase/psicologia , Índice de Gravidade de Doença , Fatores de Tempo
13.
J Eur Acad Dermatol Venereol ; 29(3): 468-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25087839

RESUMO

BACKGROUND: In clinical practice, patients with psoriasis may require intermittent therapy as part of their long-term treatment programme. Those achieving Physician's Global Assessment (PGA) of ≤ 1 (almost clear/clear) are more likely to be selected as candidates for intermittent therapy than those with a higher PGA (≥ 2; mild or worse), who may relapse sooner or have a delayed response. The objective of this analysis was to determine if patients achieving PGA ≤ 1 using intermittent etanercept (ETN) therapy could regain response (defined as PGA ≤ 2) after relapse. METHODS: In the CRYSTEL study (clinicaltrials.gov NCT00195507), patients with moderate-to-severe psoriasis were treated with ETN 50 mg twice weekly (BIW) for ≤ 12 weeks (or for an extra 12 weeks with ETN 25 mg BIW until PGA ≤ 2 was achieved). Patients who reached PGA ≤ 1 during this time were selected for this post hoc analysis (Cycle 1). Treatment was paused, and patients who relapsed (PGA > 2) were retreated with ETN 25 mg BIW until recovery (PGA ≤ 2, Cycle 2). Treatment cycles were continued for up to 54 weeks. The proportion of PGA responders and the time to attain response were calculated, and patient satisfaction was evaluated using the Patient Satisfaction Survey. RESULTS: During Cycle 1, 131 patients achieved PGA ≤ 1 within a median of 9 weeks and subsequently relapsed after treatment cessation. In Cycle 2, 119 (91%) patients attained PGA ≤ 2 within a median time of 7 weeks. The majority of patients were either 'very satisfied', 'satisfied' or 'somewhat satisfied' during both Cycle 1 (100% in total) and Cycle 2 (97% in total). CONCLUSION: Patients achieving the stringent criteria of PGA ≤ 1 with ETN therapy before ceasing treatment, and subsequently relapsing, were able to quickly regain response during retreatment. The majority of patients considered their therapy to be satisfactory.


Assuntos
Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Esquema de Medicação , Etanercepte/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
14.
J Eur Acad Dermatol Venereol ; 28(1): 108-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22845050

RESUMO

BACKGROUND: α-Melanocyte-stimulating hormone (α-MSH) is a melanocortin peptide that increases skin pigmentation during ultraviolet light-mediated tanning. As α-MSH has been shown to possess anti-inflammatory effects, we assessed the clinical potential of a superpotent α-MSH analogue, afamelanotide (Nle(4)-D-Phe(7)-α-MSH), in patients with acne vulgaris, the most common inflammatory skin disorder. METHODS: Afamelanotide (16 mg) was given in a phase II open-label pilot study subcutaneously as a sustained-release resorbable implant formulation to 3 patients with mild-to-moderate facial acne vulgaris. Evaluation included lesion count, adverse effects and patient-reported outcome. Monitoring of laboratory parameters included differential blood counts, electrolytes, urine analysis, and liver and kidney function tests. Skin melanin density was measured by reflectance spectrophotometry. RESULTS: The total number as well as the number of inflammatory acne lesions declined in all patients 56 days after the first injection of afamelanotide. Life quality as measured by Dermatology Life Quality Index likewise improved in all 3 patients 56 days after the first injection of afamelanotide. There were no adverse effects except mild and short-term fatigue in one patient. All patients experienced increased pigmentation especially on the face. Clinically relevant changes in laboratory parameters were not detected. CONCLUSIONS: Afamelanotide appears to have anti-inflammatory effects in patients with mild-to-moderate acne vulgaris. Future trials are needed to confirm the anti-inflammatory action of this melanocortin analogue in patients with acne vulgaris.


Assuntos
Acne Vulgar/tratamento farmacológico , alfa-MSH/análogos & derivados , Acne Vulgar/fisiopatologia , Implantes de Medicamento , Humanos , Projetos Piloto , Qualidade de Vida , alfa-MSH/administração & dosagem , alfa-MSH/uso terapêutico
16.
G Ital Dermatol Venereol ; 149(5): 483-503, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25077886

RESUMO

Being the largest organ of the human body, skin is frequently affected in many rheumatic diseases. Thus, it can serve as an important indicator for the correct diagnosis of a rheumatic disease and also as a marker of disease activity in distinct rheumatic disorders. In this review we will highlight the clinical features of these cutaneous manifestations of the major rheumatic diseases. We will also provide an update on the complex pathobiology of these diseases based on the most recent developments in clinical and translational research.


Assuntos
Doenças Reumáticas/patologia , Pele/patologia , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/fisiopatologia , Humanos , Doenças Reumáticas/fisiopatologia , Pele/irrigação sanguínea , Pele/fisiopatologia
18.
Gesundheitswesen ; 75(8-9): e108-12, 2013 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-23175164

RESUMO

AIM: The introduction of quality management systems might be promoted by use of recognised certification programmes. Over the years, in health care organisations the certification model named KTQ has gained more and more importance. The aim of this study is to evaluate intra-organisational effects in a clinic after introduction of quality management on the basis of KTQ. METHODS: The evaluation was performed using a 2-step approach: first, before starting the implementation process of KTQ in the year 2008, and second, after the implementation process had become successful. Data were obtained by a systematic questionnaire survey. Hospital staff (physicians, nurses, and others like administration staff, technical and medical assistants) were asked to appraise the quality management, to give own preferences, and rate their overall satisfaction with the process. RESULTS: Response rates were 56% in the year 2008 and 50% in the year 2010. Subjects regarding the working atmosphere, leading of superiors, organisational issues, and pervasion of quality management predominantly were found to be improved, almost with high statistical significance. At the same time, higher satisfaction values could be determined. CONCLUSIONS: There might be high acceptance to the undergone changes from the staff members' point of view. It appears that the implementation process has led to higher satisfaction values. Moreover it can be concluded that certification programmes might be able to promote the needed pervasion of quality management throughout the institution.


Assuntos
Atitude do Pessoal de Saúde , Certificação/organização & administração , Eficiência Organizacional/estatística & dados numéricos , Administração Hospitalar/normas , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde/normas , Gestão da Qualidade Total/normas , Eficiência Organizacional/normas , Alemanha , Administração Hospitalar/estatística & dados numéricos , Relações Interdepartamentais , Inquéritos e Questionários , Gestão da Qualidade Total/estatística & dados numéricos
19.
J Eur Acad Dermatol Venereol ; 26(4): 503-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21569118

RESUMO

BACKGROUND: Although diphenylcyclopropenone (DCP) is frequently used for the treatment of alopecia areata (AA), large studies with more than 100 patients are still scarce. OBJECTIVE: To determine the efficacy of DCP immunotherapy in a large cohort of patients with AA who had been treated in our institute from January 2000 to December 2006. METHODS: A total of 142 patients with AA undergoing topical DCP therapy in a self-controlled design were evaluated retrospectively. RESULTS: Seven patients (4.9%) were anergic to DCP. Two of 135 patients (1.5%) discontinued DCP therapy because of adverse effects. Fifty-one patients (37.8%) had a complete response (CR: >90% re-growth of hair), 20 patients (14.8%) exhibited a partial response (PR: >50-90% re-growth), 26 patients (19.3%) experienced a minimal response (MR: 10-50% re-growth) and 38 patients (28.1%) had no response after DCP therapy (NR: <10% re-growth). Bivariate logistic analysis revealed that severity of hair loss at the beginning of DCP (P=0.001) is the only significant prognostic factor for therapeutic outcome. Twenty-three patients (45.1%) with CR had relapses upon discontinuation of the treatment or even during prolonged DCP therapy. CONCLUSION: Topical immunotherapy with DCP of patients with AA is rather effective and mostly well tolerated. The extent of hair loss before therapy is the main predictor for the therapeutic success of DCP. However, DCP therapy is associated with a high degree of relapse of which patients should be well informed.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Ciclopropanos/uso terapêutico , Imunoterapia , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Ciclopropanos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
J Eur Acad Dermatol Venereol ; 26(1): 71-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22168776

RESUMO

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy profile of pegylated interferon α-2b (PEG-IFN α-2b) in combination with photochemotherapy (PUVA) in the treatment of cutaneous T-cell lymphoma (CTCL) in comparison with standard IFN α plus PUVA. DESIGN: Retrospective cohort study over a period of 7 years. PATIENTS AND INTERVENTIONS: A total of 17 consecutive CTCL patients (stage IA-IV) were retrospectively analysed for toxicity and response rates associated with PEG-IFN α-2b (1.5 µg/kg weekly) plus PUVA (n = 9) or standard IFN α-2a (9 MIU 3×/week) plus PUVA (n = 8). MAIN OUTCOME MEASURES: Differences of response rates (complete/partial remission), progression-free survival, discontinuation of therapy, safety and toxicity profiles according to World Health Organization - Common Terminology Criteria of Adverse Events (WHO-CTCAE). RESULTS: Myelosuppression and liver toxicity occured more frequently during PEG-IFN α-2b plus PUVA treatment than during standard IFN α-2a plus PUVA therapy [77.8 vs. 50% (odds ratio 1.477) and 77.8 vs. 50% (odds ratio 1.692), respectively]. By contrast, the occurence of constitutional side-effects (mainly fatigue) [100 vs.77.8% (odds ratio 0.889)] and more adverse events leading to study discontinuation was considerably higher in the standard IFN α-2a plus PUVA group. The overall response rate in the PEG-IFN α-2b plus PUVA group (89%) was significantly superior. CONCLUSIONS: In patients with cutaneous T-cell lymphoma PEG-IFN α-2b plus PUVA might become a promising treatment alternative as its higher rate of myelosuppression and liver toxicity is outweighed by its lower percentage of constitutional side-effects, and its significantly higher overall response. Due to the small number of participants at this retrospective study, a larger prospective study is essential to verify our results.


Assuntos
Ficusina/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Terapia PUVA , Fármacos Fotossensibilizantes/uso terapêutico , Polietilenoglicóis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Feminino , Ficusina/administração & dosagem , Ficusina/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
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