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1.
Respir Med ; 140: 11-20, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29957271

RESUMEN

BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients. METHODS: In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically. RESULTS: 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization. CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Biopsia , Niño , Preescolar , Esquema de Medicación , Femenino , Edad Gestacional , Glucocorticoides/administración & dosificación , Enfermedad del Almacenamiento de Glucógeno/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno/patología , Humanos , Lactante , Pulmón/patología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Masculino , Enfermedades Raras/diagnóstico , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/patología , Sistema de Registros , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
2.
Br J Dermatol ; 167 Suppl 2: 1-13, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881582

RESUMEN

BACKGROUND: During recent years numerous studies have suggested that personal and environmental factors might influence cancer development. OBJECTIVES: To investigate environmental and personal characteristics associated with skin cancer risk. METHODS: A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control persons. Exposures were assessed by questionnaires that were partly self-administered, partly completed by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of certain drugs and food items on skin cancer risk. RESULTS: The usual associations were observed for sun exposure and pigmentation characteristics, with chronic sun exposure being most strongly associated with SCC risk, and naevi and atypical naevi with CMM risk. Use of ciprofloxacin was associated with a decreased risk of BCC [odds ratio (OR) 0·33] and use of thiazide diuretics was associated with an increased risk of SCC (OR 1·66). Ciprofloxacin was also associated with SCC (OR 0·34) and thiazines with BCC (OR 2·04), but these associations lost significance after correction for multiple testing. Consumption of pomegranate, rich in antioxidants, was associated with decreased BCC and SCC risk, also after correcting for multiple testing. Recent experience of stressful events was associated with increased risk, particularly of CMM. CONCLUSIONS: In this large case-control study from across Europe the expected associations were observed for known risk factors. Some new potential protective factors and potential risk factors were identified for consumption of certain food items, medication use and stress, which deserve further investigation in future studies.


Asunto(s)
Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Dieta/efectos adversos , Erupciones por Medicamentos/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios
3.
Br J Dermatol ; 167 Suppl 2: 14-21, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881583

RESUMEN

BACKGROUND: Skin cancer can largely be prevented by avoiding unsafe ultraviolet radiation (UVR) exposure. The evidence on potential drivers of sunscreen and sunbed use is extensive, yet in some cases, such as education, remains rather unclear. Health literacy is receiving increasing attention, but its effect on tanning decisions has not yet been explored. OBJECTIVES: To explore the association between health literacy and tanning behaviour, in terms of sunscreen and sunbed use. METHODS: Self-reported data were collected through a common questionnaire in eight European countries under a common protocol. A three-item measure was used to assess health literacy; one item was collected to measure current sunscreen use and one item to measure current sunbed use. Descriptive statistics and analysis of variance tests were applied to explore the profile of sunbed and sunscreen users and health literacy among a number of variables. Univariate and multivariate logistic regressions were used to assess the relation between health literacy and sunscreen and sunbed use. RESULTS: Univariate results suggested that health literacy has opposite effects on sunscreen use vs. sunbed use. Increased health literacy was associated with the skin cancer protective practice of using sunscreen, but also with more sunbed use. In the multivariate models, health literacy had a significant effect only on sunscreen use. CONCLUSIONS: The findings suggest that health literacy can be an interesting approach for influencing sunscreen use. In the case of sunbeds, based on the findings and contrary to what was expected, it can be argued that interventions targeting health literacy seem less likely to reduce sunbed use. More research is needed to elucidate the effect of health literacy on sunscreen and sunbed use in order to improve UVR prevention strategies.


Asunto(s)
Alfabetización en Salud , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Baño de Sol/psicología , Protectores Solares/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Europa (Continente) , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/psicología , Análisis de Regresión , Neoplasias Cutáneas/psicología , Adulto Joven
4.
Br J Dermatol ; 167 Suppl 2: 29-35, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881585

RESUMEN

BACKGROUND: A wide variety of both surgical and nonsurgical therapies is currently available for patients with skin cancer. OBJECTIVES: This part of the EPIDERM (European Prevention Initiative for Dermatological Malignancies) project is aimed at the evaluation of the treatment preferences for skin cancer in eight countries of the European Union. METHODS: A multicentre hospital-based case-control study was carried out at dermatology departments in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain. Patients with skin cancer (basal cell carcinoma, actinic keratosis, squamous cell carcinoma, cutaneous malignant melanoma and Bowen disease) were consecutively enrolled between July 2008 and July 2010. Information on the study variables (sex, age, country, tumour type, anatomical location and treatment) was obtained from questionnaires designed by the EPIDERM project. RESULTS: In total, 1708 patients with skin cancer were included. Surgery was the first treatment option in 76·5% of the patients (P = 0·001). Actinic keratosis was the only tumour type in which nonsurgical treatment was more frequent than surgery (91·4%). Tumours on the head were less likely to be surgically excised than those at other locations (odds ratio 0·25, P = 0·001). Simple excision or curettage was the most common surgical procedure (65·4%), followed by graft and flaps (22·4%). Cryotherapy was the most common nonsurgical option (52·4%), followed by imiquimod (18·0%), photodynamic therapy (PDT; 12·0%), 5-fluorouracil (5-FU; 5·7%), and diclofenac with hyaluronic acid (4·0%). CONCLUSIONS: Surgery remains the first-choice treatment of skin cancer. Regarding nonsurgical treatments, the conservative treatments available (imiquimod, 5-FU, PDT and diclofenac gel) have not yet exceeded the use of ablative options such as cryotherapy despite their accepted benefit of treating field cancerization.


Asunto(s)
Actitud del Personal de Salud , Dermatología , Neoplasias Cutáneas/terapia , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Europa (Continente) , Humanos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias Cutáneas/psicología
5.
Br J Dermatol ; 167 Suppl 2: 36-42, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881586

RESUMEN

BACKGROUND: There are limited data regarding the association of actinic keratosis (AK) and other types of nonmelanoma skin cancer (NMSC); studies investigating possible correlation of AK with melanocytic naevi are even scarcer. To our knowledge, there are no data examining the risk of AK in people using specific medications. OBJECTIVE: To investigate constitutional and exposure risk factors leading to AK and the coexistence of AK with NMSC and melanoma. METHODS: A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 343 patients with actinic keratosis (AK), 409 with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC), 360 with invasive melanoma and 119 with in situ melanoma, and 686 control subjects. Exposures were assessed by questionnaires that were partly self-administered and partly filled out by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of phenotypic characteristics, presence of naevi, sun-exposure habits and certain drugs on AK risk. RESULTS: Differences in hair and eye coloration variably influenced the risk for AK, with red hair signifying a seven times higher risk [odds ratio (OR) 6·9, 95% confidence interval (CI) 4·34-11·00), and brown - compared with blue - eyes, about a 40% reduced risk (OR 0·61, 95% CI 0·13-0·92). The darker the skin phototype, the lower the risk for AK, with phototype IV exhibiting nine times less risk of developing AK. Some and many freckles on the arms were associated with an OR of 1·8 (95% CI 1·08-2·81) and 3·0 (95% CI 1·10-3·54), respectively, while overall number of naevi and high educational level were inversely associated with AK. Sun exposure, thiazide diuretics and cardiac drugs had a higher risk for AK. SCC was the most frequent (58%) skin neoplasm coexisting with AKs, followed by BCC (30%), melanoma in situ (12%) and invasive melanoma (6%). CONCLUSION: In this large case-control study from across Europe the expected associations were confirmed for known risk factors. Some possible new risk factors, including cardiac and diuretic drugs, were identified, creating a new field for further investigation in future studies.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Queratosis Actínica/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Fármacos Dermatológicos/uso terapéutico , Exposición a Riesgos Ambientales/análisis , Europa (Continente)/epidemiología , Femenino , Humanos , Queratosis Actínica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Rayos Ultravioleta/efectos adversos
6.
Br J Dermatol ; 167 Suppl 2: 43-52, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881587

RESUMEN

BACKGROUND: There are poorly documented variations in the journey a skin cancer patient will follow from diagnosis to treatment in the European Union. OBJECTIVES: To investigate the possible difficulties or obstacles that a person with a skin malignancy in the European Union may have to overcome in order to receive adequate medical screening and care for his/her condition. In addition, we wished to explore differences in European health systems, which may lead to health inequalities and health inequities within Europe. METHODS: Ten European countries took part in this investigation (in alphabetical order): Finland, Germany, Greece, Italy, Malta, Poland, Romania, Spain, the Netherlands and the U.K. The individual participants undertook local and national enquiries within their own country and completed a questionnaire. RESULTS: This exercise has identified important differences in the management of a skin cancer patient, reflecting major disparities in health care between European countries. CONCLUSIONS: Further investigation of health disparities and efforts to address health inequalities should lead to improvements in European health care quality and reduction in morbidity from skin cancer.


Asunto(s)
Disparidades en Atención de Salud/estadística & datos numéricos , Neoplasias Cutáneas/terapia , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Costos y Análisis de Costo , Fármacos Dermatológicos/economía , Fármacos Dermatológicos/uso terapéutico , Dermatología , Costos de los Medicamentos , Unión Europea , Médicos Generales/provisión & distribución , Disparidades en Atención de Salud/economía , Humanos , Guías de Práctica Clínica como Asunto , Derivación y Consulta/estadística & datos numéricos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/economía , Recursos Humanos
7.
Br J Dermatol ; 167 Suppl 2: 63-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881589

RESUMEN

BACKGROUND: Skin neoplasms are the most frequent types of neoplasms in white populations, and their incidence is increasing. Epidemiological studies have shown that the major environmental aetiological factor for their development is sunlight exposure. Sun protection programmes are urgently needed to raise awareness of the health hazards of ultraviolet radiation. In 2010 the 'SunPass' project was implemented at 55 kindergartens in Germany. This is the first nationwide environmental education programme for sun safety designed to teach children in kindergartens and their caregivers how to protect themselves from overexposure to the sun. OBJECTIVES: An interventional lecture, site inspections and a certification were part of the programme. Effects of these interventions were studied. METHODS: The gain in knowledge and changed sun-behavioural attributes were quantified by questionnaires administered before and after the 'SunPass' interventions. RESULTS: The total number of children was 5424. Sun-protection behaviour after the intervention improved significantly (P < 0·001). Among parents, 22·2% reported one to five sunburns of their child since birth. There was a significant increase in hat use by children in kindergartens (P = 0·029), as well as some significantly improved shade practices. There was a significantly increased demand for protective clothing for children (P < 0·001). The change in sunscreen use in kindergartens was not significant. CONCLUSIONS: Although some aims of the 'SunPass' project were not fulfilled, such as the precise knowledge of skin types and a change of sunscreen use, the study had some positive outcomes in increasing the awareness of skin cancer and its prevention possibilities. The findings of the present study suggest that relatively brief interventions in kindergartens lead to improved sun protection of children. The whole investigation reaching over 5400 children and their parents underlines the importance of learning appropriate sun-protective behaviour in early childhood in order to decrease the risk for skin cancer.


Asunto(s)
Neoplasias Cutáneas/prevención & control , Protectores Solares/uso terapéutico , Niño , Preescolar , Protocolos Clínicos , Docentes , Alemania , Promoción de la Salud , Humanos , Lactante , Ropa de Protección , Servicios de Salud Escolar , Quemadura Solar/prevención & control
8.
Br J Dermatol ; 167 Suppl 2: 53-62, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881588

RESUMEN

BACKGROUND: Behavioural interventions to reduce exposure to ultraviolet radiation (UVR) can reduce risk of skin cancer. OBJECTIVES: To integrate the data and to evaluate the impact of interventions to limit exposure to UVR on skin cancer incidence in four selected countries. METHODS: Using PREVENT, a dynamic simulation model, we modelled the potential for skin cancer prevention in four European countries under various scenarios to avoid damage by UVR. RESULTS: In general, the most effective interventions were those aimed at protecting people during outdoor work and outdoor hobbies against the harmful effects of UVR, and combinations of several interventions. These could in theory lead to reductions of up to 45% in skin cancer cases projected for the year 2050. CONCLUSIONS: The scope for prevention depends on the prevalence of the risk factors in the different countries, as well as the associated risk factors and time lags modelled.


Asunto(s)
Carcinoma Basocelular/prevención & control , Carcinoma de Células Escamosas/prevención & control , Melanoma/prevención & control , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Rayos Ultravioleta/efectos adversos , Anciano , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Europa (Continente)/epidemiología , Femenino , Conductas Relacionadas con la Salud , Humanos , Incidencia , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Prevalencia , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Baño de Sol/estadística & datos numéricos , Protectores Solares/uso terapéutico
9.
Br J Dermatol ; 167 Suppl 2: 85-93, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22881592

RESUMEN

Ultraviolet radiation (UVR) exposure from the sun and artificial UV sources has been widely acknowledged as the major culprit for skin cancer and premature skin ageing. Skin cancers are among the most dangerous (cutaneous malignant melanoma) and the most numerous (basal cell carcinoma, actinic keratosis and invasive squamous cell carcinoma) of all neoplasms in the caucasian population worldwide. Skin cancers therefore have a significant impact on public health and healthcare costs, and will continue to do so. It is obvious that adequate photoprotection - seeking shade, wearing protective clothing and using sunscreens - is the key to reducing the harmful effects of UVR in both immunocompetent and immunocompromised people. This article provides background information on UVR, photoprotection (including the concept of topical sunscreen formulations), associated concerns regarding efficacy and safety, and behavioural and educational aspects of photoprotection and skin cancer prevention in immunocompetent and immunocompromised people. Certain persistent misconceptions and mistakes regarding photoprotection are also addressed.


Asunto(s)
Inmunocompetencia/efectos de la radiación , Huésped Inmunocomprometido/efectos de la radiación , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Protectores Solares/uso terapéutico , Rayos Ultravioleta/efectos adversos , Humanos , Neoplasias Inducidas por Radiación/inmunología , Educación del Paciente como Asunto , Ropa de Protección , Dosis de Radiación , Conducta de Reducción del Riesgo , Neoplasias Cutáneas/inmunología , Resultado del Tratamiento , Deficiencia de Vitamina D/etiología , Deficiencia de Vitamina D/prevención & control
11.
Br J Dermatol ; 161 Suppl 3: 5-12, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19775351

RESUMEN

BACKGROUND: Nonmelanoma skin cancer (NMSC) and malignant melanoma (CMM) are among the most common malignancies in the white population. The major risk factor for those malignancies is ultraviolet radiation (UV) causing directly DNA damage and promoting the development of skin cancer. It is suggested that the exposure to UV during childhood elevates an individual's lifetime risk of developing skin cancer more than exposure in adulthood. Since an increasing number of children spend the time of the most intense UV in a day-care centre, it seems an excellent place for establishing primary skin cancer prevention. Important targets are staff members and parents of the day-care centre, since sun protection of children depends directly on their knowledge and their attitude towards sun protection practices. OBJECTIVES: To establish a feasible certification program for sun protection in a German child day-care centre, for a better sun protection of the children and the reduction of skin cancer incidence in the long term. METHODS: Initially sun protection practices of the centre at baseline were assessed. A written sun protection policy was developed in consultation with all members of the day-care centre as basis for certification. It was followed by training sessions for staff members (n=12) and parents (n=46). After a fixed period of time the final assessment of the child day-care centre was conducted and the centre then was certified for improved sun protection practices and better protection of the children. The primary assessed outcomes were the gain in knowledge of staff members and parents after the training sessions, the number of children wearing a hat when playing outside, the use of sunscreen and the percentage of shaded areas on the playground. RESULTS: Sun protection was an issue more discussed during the time of intervention than before. Staff members (n=12) and parents (n=27) had a significant gain in knowledge (staff members: P=0.002; parents: P=0.001) concerning sun related issues. The number of children wearing a hat increased from 13.2% to 73%. The sunscreen use increased, 58.8% of staff members reported a more regular application of sunscreen to the children. There was a higher percentage of shaded area on the playground (70-80% before intervention, 90% after intervention). The intervention failed in keeping the children inside during the most intense UV and in educating the staff members to be a convincing example of sun protection by wearing appropriate clothes. CONCLUSIONS: The intervention showed that the introduction of a simple certification program including a written sun protection policy and training sessions for staff members and parents helps to improve children's sun protection. We suggest that a certificate for adequate sun protection acts as a motivating factor. It seems important to refresh sun protection practices each year by repeating training sessions and reviewing the sun protection policy.


Asunto(s)
Guarderías Infantiles , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control , Certificación , Niño , Preescolar , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Recién Nacido , Masculino , Responsabilidad Parental , Proyectos Piloto , Servicios Preventivos de Salud , Ropa de Protección/estadística & datos numéricos , Protectores Solares/administración & dosificación , Encuestas y Cuestionarios
12.
Endocr Relat Cancer ; 12(4): 823-37, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16322324

RESUMEN

Early placenta insulin-like growth factor (EPIL) is expressed by a subpopulation of the Her2-positive SKBR3 breast cancer cell line displaying high motility and transendothelial invasiveness in vitro, as recently shown by our group. As a consequence of this, we established cellular models by generating an EPIL-overexpressing SKBR3 cell line, knocked down EPIL by adding specific small interfering RNA (siRNA) to those cells and produced EPIL-enriched and depleted serum-free culture media. EPIL-expressing cells as well as EPIL-induced SKBR3 cells acquired a high capacity for transendothelial invasiveness. We observed a thin and outspread morphology caused by enhanced formation of lamellipodia, i.e. protrusions in the initial phase of motility. In parallel, Her2-positive MDAHer2 breast cancer cells also showed increased invasiveness when induced by EPIL-conditioned medium. A downstream signaling impact of EPIL could be observed in the form of reduced phosphorylation of Her2, erk1/2 and akt, while phospholipase Cgamma1 phophorylation remained unaffected. As an in vivo model for highly motile tumor cells, Paget's disease of the nipple showed simultaneous EPIL and Her2 expression upon immunohistochemical examination using specific antibodies. Such experimental data have been translated to a clinical setting by using a prognostic tissue microarray established from 603 breast cancer cases. Survival data analysis found a significant association between expression levels of EPIL and 5-year overall survival that was dose dependent: EPIL (negative) 84%, EPIL (moderately positive) 77%, EPIL (strongly positive) 48% (P < 0.005). One particular subgroup (7.6% of the cases with full clinical records) that comprised tumors simultaneously expressing EPIL and Her2 represented patients with the poorest 5-year overall survival. The results suggested that EPIL might be a cancer cell-produced growth factor that influences lateral Her2 signaling. Moreover, EPIL may be induced by factors apart from Her2 and may independently provide signaling for cancer invasion and motility.


Asunto(s)
Comunicación Autocrina , Neoplasias de la Mama/diagnóstico , Movimiento Celular , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Receptor ErbB-2/metabolismo , Comunicación Autocrina/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Medios de Cultivo Condicionados/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Femenino , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intercelular/análisis , Péptidos y Proteínas de Señalización Intercelular/genética , Invasividad Neoplásica , Enfermedad de Paget Mamaria/metabolismo , Enfermedad de Paget Mamaria/patología , Pronóstico , Análisis por Matrices de Proteínas , ARN Interferente Pequeño/genética , Receptor ErbB-2/análisis
13.
Br J Cancer ; 92(9): 1720-8, 2005 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-15841074

RESUMEN

The objective of this study was to investigate expression of various growth factors associated with angiogenesis and lymphangiogenesis and of their receptors in ductal carcinomas in situ of the breast (DCIS). We studied protein expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)-A, endothelin (ET)-1, and VEGF-C, and their receptors bFGF-R1, Flt-1, KDR, ET(A)R, ET(B)R, and Flt-4 immunohistochemically in 200 DCIS (pure DCIS: n=96; DCIS adjacent to an invasive component: n=104) using self-constructed tissue microarrays. Basic fibroblast growth factor-R1, VEGF-C, Flt-4, and ET(A)R were expressed in the tumour cells in the majority of cases, whereas bFGF and Flt-1 expression was rarely observed. VEGF-A, KDR, ET-1, and ET(B)R were variably expressed. The findings of VEGF-C and its receptor Flt-4 as lymphangiogenic factors being expressed in tumour cells of nearly all DCIS lesions and the observed expression of various angiogenic growth factors in most DCIS suggest that in situ carcinomas are capable of inducing angiogenesis and lymphangiogenesis. Moreover, we found a higher angiogenic activity in pure DCIS as compared to DCIS with concomitant invasive carcinoma. This association of angiogenic factors with pure DCIS was considerably more pronounced in the subgroup of non-high-grade DCIS (n=103) as compared with high-grade DCIS (n=94). Determination of these angiogenic markers may therefore facilitate discrimination between biologically different subgroups of DCIS and could help to identify a particularly angiogenic subset with a potentially higher probability of recurrence or of progression to invasiveness. For these DCIS, targeting angiogenesis may represent a feasible therapeutic approach for prevention of progression of DCIS to invasion.


Asunto(s)
Biomarcadores/análisis , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/patología , Endotelina-1/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Análisis por Matrices de Proteínas , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
14.
Pediatr Transplant ; 9(2): 215-9, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15787796

RESUMEN

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.


Asunto(s)
Agammaglobulinemia/etiología , Trasplante de Hígado/efectos adversos , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/inmunología , Atresia Biliar/cirugía , Niño , Inmunodeficiencia Variable Común/etiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Fallo Hepático Agudo/cirugía , Subgrupos Linfocitarios
15.
Pediatr Transplant ; 8(2): 185-8, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15049800

RESUMEN

Pharmacokinetic studies in adult and pediatric liver transplant recipients have shown that the C(2) monitoring is superior to the traditional determination of CsA trough levels (C(0)) as an estimate of CsA exposure. However, target reference values for C(2) in very small infants have not been established yet. The objective of our study was to assess the distribution of C(2) levels in the first week following Ltx and to analyze enteral absorption of CsA for this group of patients. We documented CsA C(0) and C(2) levels in 25 infants with a body weight below 10 kg (median 6.8 kg; range 3.0-9.8 kg) in the first 7 days after Ltx. The infants had a median age at transplantation of 7 months (range 0.3-20.0 months). The underlying diagnoses were biliary atresia (n = 17), acute liver failure (n = 4), metabolic disease (n = 4). All children received CsA microemulsion (Neoral, initial 10 mg/kg/day), prednisolone, and two single doses of basiliximab as immunosuppressive drugs. The mean C(0) and C(2) levels were as follows: day 1: C(0) 77.0 +/- 39.6, C(2) 340.5 +/- 140.0 ng/mL; day 2: C(0) 135.5 +/- 53.2, C(2) 467.0 +/- 168.2 ng/mL; day 3: C(0) 146.5 +/- 70.8, C(2) 519.0 +/- 219.1 ng/mL; day 4: C(0) 168.5 +/- 55.1, C(2) 570.0 +/- 163.7 ng/mL; day 5: C(0) 156.5 +/- 38.0, C(2) 612.0 +/- 132.4 ng/mL; day 6: C(0) 177.0 +/- 41.1, C(2) 606.0 +/- 149.2 ng/mL; day 7: C(0) 174.0 +/- 27.2, C(2) 622.0 +/- 98.8 ng/mL (r = 0.82, p < 0.05). This analysis demonstrates that there is a good enteral absorption of CsA in very small children post-Ltx in the early post-operative period. Based on the C(2) levels achieved, we conclude that there is a good correlation between C(0) and C(2) levels even in very small infants.


Asunto(s)
Peso Corporal , Ciclosporina/sangre , Inmunosupresores/sangre , Trasplante de Hígado , Administración Oral , Anticuerpos Monoclonales/uso terapéutico , Basiliximab , Atresia Biliar/cirugía , Ciclosporina/administración & dosificación , Monitoreo de Drogas , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/administración & dosificación , Lactante , Absorción Intestinal , Fallo Hepático Agudo/cirugía , Enfermedades Metabólicas/cirugía , Prednisolona/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico
16.
Med Device Technol ; 14(1): 20-5, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12974121

RESUMEN

The annealing process is an important key step in the manufacture of high quality and reliable 316 LVM stents. [figure: see text] The methods commonly applied for verifying the outcome of the annealing process such as microhardness testing are inappropriate and should not be used. The tension testing of tubes, processed together with stents, provides reliable results of the final material properties of stents. During the course of the investigation the grain size was reduced significantly and the break elongation improved. The surface of the strain-tested material shows substantial improvements. All results are particularly important for thin-wall stents with filigree struts.


Asunto(s)
Materiales Biocompatibles/química , Calor , Diseño de Prótesis/métodos , Acero Inoxidable/química , Stents , Materiales Biocompatibles/síntesis química , Elasticidad , Análisis de Falla de Equipo/métodos , Dureza , Movimiento (Física) , Falla de Prótesis , Control de Calidad , Estrés Mecánico , Propiedades de Superficie , Resistencia a la Tracción
17.
J Clin Pathol ; 56(9): 660-5, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12944548

RESUMEN

BACKGROUND: Bilaterality in breast cancer is a rare event and together with an early onset of disease points towards inheritance of the disease. However, most cases seem to occur sporadically, either in a synchronous or metachronous manner. METHODS: Thirty two invasive carcinomas and one in situ carcinoma from 16 patients with synchronous, bilateral breast cancer were investigated by means of comparative genomic hybridisation (CGH) and polymerase chain reaction based multiplex microsatellite analysis. The results were analysed conventionally and were also subjected to a biomathematical cluster analysis. RESULTS: On average, bilateral breast cancer cases showed a low number of genetic alterations, a low frequency of genetic amplifications, and a high rate of chromosomal 16q losses. A distinct, characteristic genetic alteration associated with bilateral breast disease could not be found. Although two tumour pairs appeared to be related using biomathematical processing for microsatellite analysis, this result was reproduced by CGH data processing in one patient only. CONCLUSIONS: Most synchronous, bilateral breast cancer cases seem to represent independent tumours rather than metastatic events. Nevertheless, the possibility of a specific susceptibility remains.


Asunto(s)
Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Aberraciones Cromosómicas , Neoplasias Primarias Múltiples/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/genética , Análisis por Conglomerados , Femenino , Humanos , Pérdida de Heterocigocidad , Repeticiones de Microsatélite , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa/métodos
19.
In Vivo ; 14(5): 611-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11125545

RESUMEN

The present study investigates the role of sex steroids, especially serum estradiol and serum testosterone in male osteoporosis patients and their association to established markers of bone turnover as also to BMD results and histomorphometric findings. Included were patients with secondary osteoporosis due to steroid medication, anticonvulsive medication and alcohol consumption, and heavy smoking patients. 100 males aged from 30 to 78 years were investigated for osteodensitometry (DEXA) and assessment of biochemical bone turnover markers (venous blood samples, 24 hour urine samples). In 40 of these patients bone biopsies were taken for histomorphometry. Laboratory investigations were made for serum Ca, P, parathyroid hormone (PTH), osteocalcin (OC), carboxyterminal extension peptide of type I procollagen (PICP), bone specific alkaline phosphatase (B-ALP), 25OH-vit.D, testosterone, estradiol, gonadotropines, and deoxypyridinoline and hydroxyproline from 24-hour urinary collection. Regions of interest for osteodensitometry with DEXA technique were the lumbar spine L1-L4 and the femoral neck (Ward's triangle). All of the patients examined had low bone mineral density (BMD) values compared to age- and sex-matched controls. Results from descriptive statistics showed hypogonadism in 26.4%, 25 OH-vitamin D deficiency in 26.2% and high serum estradiol in 59.1% of patients, compared to age- and sex-matched controls. 8.5% had elevated PTH levels. Multivariate analysis of data showed no significant correlation between BMD and semiquantitative histomorphometric findings (scaled from 1-5), neither a significant correlation between serum testosterone/estradiol and BMD. A significant correlation was observed between testosterone and estradiol values (r = 0.389, p = 0.008), and between OC and BMD results at ward's triangle (p = 0.008). In steroid treated patients (n = 12) significant differences were found for PTH (P < 0.01), 25 OH-Vit.D (p < 0.05) and urinary deoxypyridinoline (p < 0.05) as compared with the other patient group (n = 88). In summary we found high serum estradiol in 59.1% of our patients collective with low BMD, there was no correlation between BMD and histomorphometric findings. We observe a significant positive correlation between testosterone and estradiol values, but we did not find any association to bone turnover markers or BMD results.


Asunto(s)
Densidad Ósea/fisiología , Estradiol/sangre , Osteoporosis/metabolismo , Osteoporosis/patología , Testosterona/sangre , Absorciometría de Fotón , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Remodelación Ósea/fisiología , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/metabolismo , Glucocorticoides/uso terapéutico , Humanos , Ilion/patología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/etiología , Valores de Referencia
20.
Pediatr Transplant ; 4(2): 156-8, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-11272610

RESUMEN

We report the occurrence of epididymitis and orchitis 1 week after the onset of Listeriosis in an 11-month-old boy receiving an orthotopic liver transplantation for biliary atresia. Immunologic implications of Listeria monocytogenes-induced testicular inflammation are discussed, and the potential role of immunosuppression with tacrolimus is also discussed.


Asunto(s)
Atresia Biliar/cirugía , Epididimitis/microbiología , Listeriosis/diagnóstico , Trasplante de Hígado , Orquitis/microbiología , Epididimitis/inmunología , Humanos , Inmunosupresores/efectos adversos , Lactante , Listeriosis/inmunología , Trasplante de Hígado/inmunología , Masculino , Orquitis/inmunología , Tacrolimus/efectos adversos
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