RESUMEN
Problem gambling has not been a priority within either Leeds City Council or partnership plans. However, financial inclusion, licencing and public health teams have been able to develop a cross-Council approach to problem gambling. This has been aided by an upfront payment plus annual payments to the Council that have been part of the licencing agreement for a new casino. As a result, research has been commissioned on local prevalence. This showed a higher rate of problem gamblers (1.8%) than national estimates with a similar level to nationally of those 'at risk'. The research also showed that local services had difficulties identifying problem gamblers and signposting for support. This had led to a high profile communications campaign to coincide with 'Responsible Gambling Week' complemented by training for frontline workers. The interviews undertaken for the research, plus the findings themselves, have been a powerful help in securing interest and commitment beyond the Council and to the health and third sectors. The use of local stories has helped build momentum for partnership working. For example, focus groups to explore how gambling affected migrants and medical student interviews with university students. The article will describe how increasing understanding across partners has helped build confidence to provide cross city responses to national consultations and contribute to national publications and conferences. Of even greater significance, the local National Health Service has secured funding from GambleAware for a Northern Gambling Service to be based in Leeds with satellites in the North East and Greater Manchester. This will provide treatment for those with severe gambling addiction. Additional support will come from a significant increased provision of GamCare services working to identify, screen and support problem gamblers. The use of Council premises for both of these services is testament to joint working. Recognising that this is a new emerging agenda has led to the creation of a Yorkshire and Humber Problem Gambling Working Group, endorsed by the Association of Directors of Public Health. This has resulted in shared learning and determining a consistent approach to harm. Even during a short time, the degree of interest has risen substantially. A regional gambling harm reduction framework has been produced that sets out a menu of actions. This intends to help local areas determine their own priorities. There is increasing recognition that problem gambling is a public health issue. Leadership requires a systems led, and Health in All Policies, approach to ensure problem gambling is not seen as a narrow niche issue led by public health staff. There is a need to recognise that engagement takes time. However, this is a new and emerging issue. The solutions to problem gambling are not clear and this allows for more creative, pragmatic and coproduced approaches.
Asunto(s)
Conducta Adictiva/prevención & control , Juego de Azar/prevención & control , Gobierno Local , Conducta Adictiva/epidemiología , Inglaterra/epidemiología , Juego de Azar/epidemiología , Juego de Azar/psicología , HumanosRESUMEN
Treatment of psoriasis with dithranol as monotherapy or dithranol in combination with UVB phototherapy is an effective and safe approach for the management of psoriasis. Recently a new formulation of dithranol embedded in crystalline monoglycerides (Micanol) has become available. It was shown that this formulation combines adequate efficacy with low irritation and staining properties. The aim of the present study was to compare and contrast three treatment schedules with respect to clinical efficacy and tolerability: Micanol monotherapy, Micanol in combination with UVB phototherapy and placebo combined with UVB phototherapy. The study design was a partly open, partly double-blind, randomized, left-right comparison. In total 36 patients were included and 24 body halves were available for each of the three treatments. The combination of Micanol with UVB resulted in clearance of lesions in 54% of the patients (body halves). Combination therapies with Micanol and either of the two other therapies were highly effective. However, with the number of patients investigated, a statistically significant difference between the three therapeutic approaches with respect to efficacy could not be shown. The three treatments resulted in a grosso modo comparable clinical improvement. Severe irritation was observed in 8% and staining of the skin in 29% of the patients treated with the combination therapy Micanol/UVB, which is far less compared to the irritation and staining by the conventional short contact approaches. The efficacy and tolerability of Micanol make this active substance an important tool in the management of psoriasis.
Asunto(s)
Antralina/administración & dosificación , Antiinflamatorios/administración & dosificación , Psoriasis/tratamiento farmacológico , Psoriasis/radioterapia , Terapia Ultravioleta , Administración Tópica , Adulto , Anciano , Antralina/efectos adversos , Antiinflamatorios/efectos adversos , Distribución de Chi-Cuadrado , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , PomadasRESUMEN
The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.
Asunto(s)
Proteínas de Filamentos Intermediarios/análisis , Precursores de Proteínas/análisis , Psoriasis/patología , Piel/química , Tenascina/análisis , Adulto , Anciano , Biopsia , División Celular/fisiología , Células Epidérmicas , Epidermis/química , Epidermis/patología , Femenino , Proteínas Filagrina , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismo , Queratinas/análisis , Queratinas/genética , Queratinas/metabolismo , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Psoriasis/metabolismo , Psoriasis/fisiopatología , Piel/patología , Piel/fisiopatología , Tenascina/genética , Tenascina/metabolismoRESUMEN
Micanol, in which dithranol is micro-encapsulated in crystalline monoglycerides, is easy to wash off and staining and irritation are inconspicuous. These features make it appropriate to use in an out-patient setting. In this study the immunohistochemical effects of this new dithranol formulation were studied and compared with UVB and the combination of these therapies in skin biopsies of 8 patients with psoriasis. Markers for epidermal differentiation, proliferation and cutaneous inflammation were assessed. The present study suggests that Micanol predominantly had diminishing effects on inflammation markers, hardly affecting the epidermis. UVB had a broad spectrum of reductions. It is feasible that the combination resulted in various synergistic effects. Previous studies, however, revealed a relative persistence of the inflammatory infiltrate with more effects on epidermal processes following dithranol treatment. Based on the present study and on previous studies, it is hypothesised that Micanol delivers the active substance more directly in the dermal infiltrate, leaving the epidermis relatively unaffected. This might explain the low irritancy of Micanol treatment.
Asunto(s)
Antralina/administración & dosificación , Psoriasis/tratamiento farmacológico , Psoriasis/radioterapia , Piel/patología , Terapia Ultravioleta , Adulto , Anciano , Cápsulas , Diferenciación Celular , División Celular , Epidermis/patología , Femenino , Humanos , Inmunohistoquímica , Inflamación , Masculino , Persona de Mediana Edad , Pomadas , Psoriasis/patologíaRESUMEN
The clinical efficacy and tolerability of the vitamin D3 analogues calcitriol, calcipotriol and 1 alpha, 24 dihydroxyvitamin D3 in the treatment of psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these compounds with epidermal growth, keratinisation and inflammation. In this study we quantified the in vivo cell biological effects during treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3. By using a flow cytometric triple labelling procedure, we could discriminate different epidermal subpopulations, permitting precise assessment of epidermal cell cycle kinetics. Twenty patients with plaque-type psoriasis were treated in a double-blind placebo-controlled left-right comparative study with 1 alpha, 24 dihydroxyvitamin D3 ointment (4 micrograms/g applied once daily) for 8 weeks. Epidermal cell suspensions prepared from keratotome biopsies taken before and after treatment were stained with TO-PRO-3 iodide (a new DNA fluorochrome) and monoclonal antibodies against keratin 10 (as a marker for differentiation) and vimentin (as a marker for inflammation), simultaneously. The flow cytometric analyses showed a significant decrease of proliferating basal keratinocytes in verum-treated lesions, whereas such a decrease was not observed in placebo-treated lesions. The amount of keratin 10-positive keratinocytes increased and the presence of vimentin-positive cells decreased in cell suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparameter flow cytometry promises to be an adequate approach to assess the interference of antipsoriatic treatments with cutaneous inflammation, epidermal proliferation and keratinisation. Topical 1 alpha, 24 dihydroxyvitamin D3 seems to exert its in vivo antipsoriatic effect mainly through an inhibition of epidermal growth.
Asunto(s)
Fármacos Dermatológicos/uso terapéutico , Dihidroxicolecalciferoles/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Biopsia , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , ADN/análisis , Fármacos Dermatológicos/administración & dosificación , Dihidroxicolecalciferoles/administración & dosificación , Método Doble Ciego , Epidermis/efectos de los fármacos , Epidermis/patología , Femenino , Citometría de Flujo , Colorantes Fluorescentes , Humanos , Inflamación , Queratinas/análisis , Masculino , Persona de Mediana Edad , Placebos , Psoriasis/patología , Vimentina/análisisRESUMEN
Platelet-activating factor (PAF) is considered to be one of the most potent lipid mediators in allergic and inflammatory reactions. Suggestions that PAF is produced by cutaneous cells, and cells infiltrating the skin from the blood, have been reported. PAF has been identified in allergic cutaneous reactions and also in psoriatic lesions. The biological activity of PAF is thought to be mediated by cell membrane receptors. Studies revealed that PAF-antagonists can be active in animal models of cutaneous inflammation. In humans PAF-antagonists showed minimal therapeutic improvement in studies of antigen-induced cutaneous responses in atopic subjects. No data are available on the effects of PAF-antagonists in psoriasis. The objective of this study was to investigate the effect of a potent PAF-antagonist (Ro 24-0238, 10% solution in diethylene glycol monoethyl ether) in 10 patients with chronic plaque psoriasis, a placebo-controlled double-blind study. Clinical response was evaluated and markers of inflammation, differentiation and proliferation were studied immunohistochemically on punch biopsies taken from actively treated and placebo-treated lesions, before and after treatment. This study demonstrated that a 10% solution of the PAF-antagonist Ro 24-0238 was not effective at the clinical or cell biological level after a 4-week treatment period. The most likely explanation for these negative observations is that PAF is not a significant factor in the pathogenesis of psoriasis.