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1.
Respir Med ; 140: 11-20, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29957271

RESUMO

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.


Assuntos
Doença de Depósito de Glicogênio/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Biópsia , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Idade Gestacional , Glucocorticoides/administração & dosagem , Doença de Depósito de Glicogênio/tratamento farmacológico , Doença de Depósito de Glicogênio/patologia , Humanos , Lactente , Pulmão/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Masculino , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Doenças Raras/patologia , Sistema de Registros , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
2.
Br J Dermatol ; 167 Suppl 2: 1-13, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881582

RESUMO

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.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dieta/efeitos adversos , Toxidermias/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
3.
Br J Dermatol ; 167 Suppl 2: 14-21, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881583

RESUMO

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.


Assuntos
Letramento em Saúde , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Banho de Sol/psicologia , Protetores Solares/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Europa (Continente) , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/psicologia , Análise de Regressão , Neoplasias Cutâneas/psicologia , Adulto Jovem
4.
Br J Dermatol ; 167 Suppl 2: 29-35, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881585

RESUMO

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.


Assuntos
Atitude do Pessoal de Saúde , Dermatologia , Neoplasias Cutâneas/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Europa (Continente) , Humanos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Cutâneas/psicologia
5.
Br J Dermatol ; 167 Suppl 2: 36-42, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881586

RESUMO

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.


Assuntos
Exposição Ambiental/efeitos adversos , Ceratose Actínica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fármacos Dermatológicos/uso terapêutico , Exposição Ambiental/análise , Europa (Continente)/epidemiologia , Feminino , Humanos , Ceratose Actínica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Raios Ultravioleta/efeitos adversos
6.
Br J Dermatol ; 167 Suppl 2: 43-52, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881587

RESUMO

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.


Assuntos
Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias Cutâneas/terapia , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Custos e Análise de Custo , Fármacos Dermatológicos/economia , Fármacos Dermatológicos/uso terapêutico , Dermatologia , Custos de Medicamentos , União Europeia , Clínicos Gerais/provisão & distribuição , Disparidades em Assistência à Saúde/economia , Humanos , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/economia , Recursos Humanos
7.
Br J Dermatol ; 167 Suppl 2: 63-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881589

RESUMO

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.


Assuntos
Neoplasias Cutâneas/prevenção & controle , Protetores Solares/uso terapêutico , Criança , Pré-Escolar , Protocolos Clínicos , Docentes , Alemanha , Promoção da Saúde , Humanos , Lactente , Roupa de Proteção , Serviços de Saúde Escolar , Queimadura Solar/prevenção & controle
8.
Br J Dermatol ; 167 Suppl 2: 53-62, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881588

RESUMO

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.


Assuntos
Carcinoma Basocelular/prevenção & controle , Carcinoma de Células Escamosas/prevenção & controle , Melanoma/prevenção & controle , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Idoso , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Prevalência , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Banho de Sol/estatística & dados numéricos , Protetores Solares/uso terapêutico
9.
Br J Dermatol ; 167 Suppl 2: 85-93, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881592

RESUMO

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.


Assuntos
Imunocompetência/efeitos da radiação , Hospedeiro Imunocomprometido/efeitos da radiação , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/uso terapêutico , Raios Ultravioleta/efeitos adversos , Humanos , Neoplasias Induzidas por Radiação/imunologia , Educação de Pacientes como Assunto , Roupa de Proteção , Doses de Radiação , Comportamento de Redução do Risco , Neoplasias Cutâneas/imunologia , Resultado do Tratamento , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/prevenção & controle
11.
Br J Dermatol ; 161 Suppl 3: 5-12, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19775351

RESUMO

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.


Assuntos
Creches , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Queimadura Solar/prevenção & controle , Certificação , Criança , Pré-Escolar , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Poder Familiar , Projetos Piloto , Serviços Preventivos de Saúde , Roupa de Proteção/estatística & dados numéricos , Protetores Solares/administração & dosagem , Inquéritos e Questionários
12.
Endocr Relat Cancer ; 12(4): 823-37, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16322324

RESUMO

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.


Assuntos
Comunicação Autócrina , Neoplasias da Mama/diagnóstico , Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptor ErbB-2/metabolismo , Comunicação Autócrina/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Invasividade Neoplásica , Doença de Paget Mamária/metabolismo , Doença de Paget Mamária/patologia , Prognóstico , Análise Serial de Proteínas , RNA Interferente Pequeno/genética , Receptor ErbB-2/análise
13.
Br J Cancer ; 92(9): 1720-8, 2005 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-15841074

RESUMO

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.


Assuntos
Biomarcadores/análise , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Endotelina-1/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Análise Serial de Proteínas , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
14.
J Clin Pathol ; 56(9): 660-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12944548

RESUMO

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.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Aberrações Cromossômicas , Neoplasias Primárias Múltiplas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/genética , Análise por Conglomerados , Feminino , Humanos , Perda de Heterozigosidade , Repetições de Microssatélites , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase/métodos
15.
In Vivo ; 14(5): 611-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11125545

RESUMO

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.


Assuntos
Densidade Óssea/fisiologia , Estradiol/sangue , Osteoporose/metabolismo , Osteoporose/patologia , Testosterona/sangue , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Remodelação Óssea/fisiologia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/metabolismo , Glucocorticoides/uso terapêutico , Humanos , Ílio/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Valores de Referência
16.
Klin Monbl Augenheilkd ; 214(6): aA7-9, 1999 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-10427534

RESUMO

BACKGROUND: A pyogenic granuloma developing after eye muscle surgery is a rare complication. It can impair aestethical results and ocular motility. PATIENT AND METHODS: A 7-year-old girl presented in our department with recurrence of a conjunctival granuloma following a bimedial retroequatorial myopexia an excision of conjunctival suture granuloma in the left eye. Clinically, a nodular painless and reddish mass was found at the nasal limbus in the interpalpebral zone. Other results of ocular examinations were limitation of adduction and elevation, mild amblyopia (visual acuity 0.8) due to microstrabismus of 1 degree. After surgical excision following the initial biopsy, the histopathologic study established the diagnosis of pyogenic granuloma. After recessing residual conjunctiva and Tenon's fascia in 10 mm distance from the limbus the conjunctiva was fixed to the sclera. The sclera between the limbus and the conjunctiva was left uncovered. Reepithelialisation of the bare sclera occurred after few days. RESULTS: No further symptoms were observed during a follow-up time of 1 year. CONCLUSIONS: The rapid growth and appearance as well as the clinical examination may imitate another tumor necessitating surgical excision and histopathological study. Bare sclera-technique is a suitable method for plastic reconstruction.


Assuntos
Granuloma Piogênico/etiologia , Músculos Oculomotores/cirurgia , Criança , Túnica Conjuntiva/cirurgia , Feminino , Seguimentos , Granuloma Piogênico/cirurgia , Humanos , Músculos Oculomotores/patologia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Complicações Pós-Operatórias/cirurgia
17.
Z Gastroenterol ; 36(3): 233-8, 1998 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-9577907

RESUMO

A 74-year-old male suffering from Recklinghausen's fibromatosis (NvR) is reported. He presented with weight loss, cholestasis, endocrine and exocrine pancreatic insufficiency. These symptoms were caused by a neuroendocrine tumor of the ampulla of Vater containing somatostatin. The tumor induced an obstruction of both the common bile and the pancreatic duct. In addition to this uncommon tumor, a silent pheochromocytoma was found. The patient was treated by endoscopic papillotomy, substitution of pancreatic enzymes and additional enteral nutrition. After recovery no progression of the disease was observed over one year. A review of the literature shows that patients with neurofibromatosis are at high risk for periampullar tumors. In particular, somatostatin-rich carcinoids were previously documented. Pheochromocytomas are also quite prevalent in NvR. However the combination of NvR, pheochromocytoma and somatostatin-rich neuroendocrine tumors of the duodenum has only been reported a few times. An explanation for the high prevalence of neuroendocrine tumors in NvR might be the loss of neurofibromin, a tumor suppressor protein, which is the main product of the neurofibromatosis-l-gene.


Assuntos
Ampola Hepatopancreática , Tumor Carcinoide/complicações , Neoplasias do Ducto Colédoco/complicações , Neoplasias Primárias Múltiplas/diagnóstico , Neurofibromatose 1/complicações , Feocromocitoma/complicações , Somatostatina/metabolismo , Idoso , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/terapia , Colestase/complicações , Colestase/diagnóstico , Colestase/terapia , Terapia Combinada , Neoplasias do Ducto Colédoco/diagnóstico , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/terapia , Diagnóstico Diferencial , Nutrição Enteral , Humanos , Masculino , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/terapia , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Cuidados Paliativos , Extratos Pancreáticos/uso terapêutico , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/terapia , Esfinterotomia Endoscópica
18.
Ann Otol Rhinol Laryngol ; 107(3): 247-53, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9525248

RESUMO

Although upper aerodigestive tract endoscopy is commonly performed, the need for hospital admission remains controversial. A retrospective review of endoscopy performed between January 1, 1993, and June 30, 1995, identified 201 patients who underwent 371 procedures. Complications occurred in 34 of 371 (9.2%) procedures in 26 of 201 (12.9%) patients. Of these, 11 of 371 (3.0%) were major (requiring admission for management) and 23 of 371 (6.2%) were minor. For multiple concurrent procedures, the overall complication rate was 19.3% (22/114); 5.3% (6/114) were major and 14.0% (16/114) were minor. All 8 patients (100%) who went on to have major complications and 24 of the 26 (92.3%) who went on to have any complication were successfully identified prior to discharge; 2 required postdischarge outpatient management of urinary retention. Five statistically significant risk factors for complication were identified: preexisting cardiac conditions, American Society of Anesthesiologists rating, airway class rating, anesthesia type, and number of endoscopic procedures performed. A comparison of various approaches to hospital admission demonstrated that selective admission based on clinical judgment was superior to routine admission of all patients. In conclusion, we recommend that upper tract endoscopy be performed on an ambulatory basis because 1) the complication rate is low, 2) complications requiring inpatient management are identifiable in the immediate postoperative period, and 3) of the approaches to hospital admission examined, it was the most economical.


Assuntos
Broncoscopia , Esofagoscopia , Hospitalização , Laringoscopia , Adulto , Assistência Ambulatorial , Broncoscopia/efeitos adversos , Criança , Esofagoscopia/efeitos adversos , Feminino , Humanos , Laringoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Anaesthesist ; 45(9): 834-8, 1996 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-8967602

RESUMO

UNLABELLED: Intraoperative autotransfusion is contraindicated in cancer surgery because of the possible risk of systemic tumor spread. The aim of the present study was to investigate whether a cell saver in combination with a white blood cell depletion filter can remove osteosarcoma cells. METHODS: A defined number of osteosarcoma cells from an established cell line were added to red cell concentrates and Ringer solution. The tumor cell concentration was 1000/ ml in the first five experiments, 7111/ml in test no. 6, 1667/ml in test no. 7 and 167/ml in test no. 8. Following thorough mixing, each unit was processed separately by a cell saver (DIDECO BT 795/P) in its normal operation mode to produce a red cell concentrate. This red cell concentrate was filtered using a leukocyte depletion filter (PALL BPF 4). Samples were taken before and after processing with the autotransfuser and after filtration with the white cell depletion filter. Cytospin specimens from all samples were examined for osteosarcoma cells by three different methods (Papanicolaou stain, Vimentin antibodies, DNA analysis). RESULTS: After processing with the autotransfuser, tumor cells were identified in the red cell concentrate. No osteosarcoma cells were evident after the combined use of cell saver and leukocyte depletion filter. CONCLUSION: The sole use of the autotransfuser DIDECO BT 795/P during osteosarcoma surgery is not recommended because of the potential danger of retransfusion of malignant cells. In combination with the leukocyte depletion filter PALL BPF 4, no osteosarcoma cells were identified in the red cell concentrate. Since the adhesiveness of tumor cells from established cell lines may be different from that of tumor cells in the intraoperative salvaged blood, further studies with blood from the surgical field are necessary to determine the efficacy of white cell depletion filters to eliminate osteosarcoma cells.


Assuntos
Transfusão de Sangue Autóloga/instrumentação , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/cirurgia , Leucócitos/fisiologia , Osteossarcoma/prevenção & controle , Osteossarcoma/cirurgia , Transfusão de Sangue Autóloga/efeitos adversos , Separação Celular , Contagem de Eritrócitos , Filtração , Humanos , Período Intraoperatório , Células Tumorais Cultivadas
20.
J Pathol ; 177(4): 385-93, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8568593

RESUMO

In order to detect early precancerous changes which do not involve the whole thickness of the epithelium, we used a novel image analysing program based on an IBAS system (Kontron, Germany) to determine nuclear DNA content (NC) as well as average nuclear area (NA) and variation of nuclear area (VA), in the entire epithelium and in three sublayers, parabasal, intermediate, and superficial. DNA aneuploidy was found in only half of the cases classified as 'high-grade' (HG) lesions, comprising carcinoma in situ (CIS) and severe epithelial dysplasias (EDIII), and was chiefly demonstrable in the parabasal third of the epithelium. The other lesions were DNA euploid. HG lesions showed highly significant increases of NA and VA at the lower levels of the epithelium when compared with 'low-grade' (LG) lesions comprising moderate and mild epithelial dysplasias (EDII and EDI). Our data show that the combination of multiparameter image analysis with conventional morphology assists in the objective grading of precancerous lesions and permits the reliable detection of high-grade lesions.


Assuntos
DNA de Neoplasias/análise , Processamento de Imagem Assistida por Computador , Neoplasias Laríngeas/ultraestrutura , Lesões Pré-Cancerosas/ultraestrutura , Adulto , Idoso , Núcleo Celular/patologia , Epitélio/ultraestrutura , Feminino , Seguimentos , Humanos , Cariometria/métodos , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Ploidias , Lesões Pré-Cancerosas/genética
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