Evolução da displasia fibrosa óssea na síndrome de McCune Albright

McCune Albright syndrome is a rare disorder characterized by polyostotic fibrous dysplasia, café-au-lait spots and some endocrine hyperfunction, mostly precocious puberty. It is caused by activating mutations of the GNAS1 gene that codifies for the Galphas protein, leading to overproduction of cAMP messenger at different tissues. Although pseudo-precocious puberty is the most frequent disfunction, the skeletal lesions are responsible for the highest morbidities such as bone pain, fractures and deformations. Clinical follow up focusing the bone disease is reported in four patients, three of them been treated with intravenous bisphosphonate (Pamidronate, 2mg/kg). Precocious puberty occurred in three and hyperthyroidism developed in two of the patients. Alkaline phosphatase (AP) levels were used as biochemical markers of the osteolytic lesions, clinically presented by local pain, fracture and bone deformities. In addition, lachrymal obstruction in one patient and unilateral blindness in another appear to be due to deformed skull and facial bones. Intravenous infusion of Pamidronate has been improving bone pain and decreased (37% - 54%) basal AP levels. However, a long-term randomized follow-up study determining improvement in bone quality still needs to be completed.A tríade clássica da Síndrome de McCune Albright (SMA) - displasia fibrosa poliostótica (DFP), máculas cutâneas café au lait e hiper-função autônoma de uma ou mais glândulas endócrinas - envolve mutações ativadoras do gene GNAS1, codificador da proteína Galfas e conseqüente aumento da produção do sinalizador intracelular AMPc em diferentes tecidos. Embora a pseudo-puberdade precoce (PPP) seja a manifestação clínica mais freqüente, são as alterações ósseas que conferem a maior morbidade à síndrome. Apresentamos o seguimento clínico endocrinológico e a evolução da doença óssea em 4 pacientes portadores da SMA, das quais 3 delas estão sendo tratadas com bisfosfonato (Pamidronato, 2mg/kg). Três das 4 pacientes apresentaram pseudo-puberdade precoce e duas delas desenvolveram hipertiroidismo. A variação do nível de fosfatase alcalina (FA) foi o indicador bioquímico da doença óssea, cujas complicações foram dor e fratura além de obstrução do canal lacrimal em uma e amaurose unilateral em outra como conseqüência das deformidades crânio-faciais. A infusão de pamidronato endovenoso produziu melhora das dores ósseas e reduziu (37% - 54%) os níveis de FA em todas as pacientes. Entretanto, a melhora da qualidade do osso com o uso do bisfosfonato ainda é incerta e para a qual necessitamos de estudos randomizados e com longo prazo de observação.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Carcinoma de paratiróide: características clínicas e anátomo-patológicas de cinco casos

Parathyroid carcinoma is a rare disease, with about 535 cases reported in the literature until now. In this paper, we reviewed 5 cases of parathyroid carcinoma followed at Universidade Federal de São Paulo (UNIFESP) from 1983 to 1998, and discuss aspects of clinical presentation, diagnosis and treatment. Four patients were female and 1 male, with median ages of 52 years (10 to 77 years). Initial clinical complains were bone pain and weight loss in 4 patients, traumatic fracture in 2, and fracture without trauma in 3. Kidney stone was present in 1 patient. All had a palpable mass in the cervical region and presented with high calcium levels: 14.9±1.7mg/dL (mean±SD). Parathyroid hormone (PTH) levels were extremely high, showing the severity of the disease. All patients had surgical exploration where a tumor mass was recognized and removed. Pathologic examination demonstrated parathyroid carcinoma in all. On follow-up, 2 patients had recurrence and died due to complications of hyperparathyroidism. To date, the other 3 patients have no evidences of recurrence.O carcinoma de paratiróide é uma entidade rara, havendo cerca de 535 casos descritos na literatura. Neste trabalho, revisamos a nossa casuística de 5 pacientes com carcinoma de paratiróide avaliados no período de 1983 a 1998 no serviço de Doenças Ósteo-Metabólicas da Universidade Federal de São Paulo (UNIFESP), analisando critérios diagnósticos, conduta terapêutica e a evolução destes pacientes e comparando os nossos dados com os achados de literatura. Entre os nossos pacientes, 4 eram do sexo feminino e 1 do sexo masculino, com mediana ao diagnóstico de 52 anos de idade, variando de 10 a 77 anos. As queixas iniciais incluíam presença de dores ósseas acompanhada de perda de peso em 4 pacientes, presença de fratura não traumática em 3 pacientes e traumática em 2 e clínica de nefrolitíase em 1 paciente. Todos apresentavam nódulo palpável em região cervical, níveis de cálcio total bastante elevados com média(±DP) de 14,9±1,7mg/dL. PTH também se encontrava muito elevado, refletindo a magnitude da severidade da doença. Todos foram submetidos à exploração cirúrgica cervical com retirada da massa tumoral, que foi coincidente com o achado palpatório de nódulo cervical. O exame anátomo-patológico revelou o diagnóstico de carcinoma de paratiróide em todos estes casos. No seguimento, 2 pacientes apresentaram recidiva tumoral e evoluíram para óbito por complicações do hiperparatiroidismo. Os outros 3 casos encontram-se em acompanhamento ambulatorial no nosso hospital, sem evidências até o momento de recidiva tumoral.Universidade Federal de São Paulo (UNIFESP) Disciplina de Endocrinologia e MetabologiaUniversidade Federal de São Paulo (UNIFESP) Disciplina de Anatomia PatológicaUniversidade Federal de São Paulo (UNIFESP) Disciplina de Cirurgia de Cabeça e PescoUNIFESP, Disciplina de Endocrinologia e MetabologiaUNIFESP, Disciplina de Anatomia PatológicaUNIFESP, Disciplina de Cirurgia de Cabeça e PescoSciEL

Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.CP received a PhD fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BD/27465/2006)

An alternative food neophobia scale (FNS-A) to quantify responses to new foods

An alternative Food Neophobia Scale (FNS-A) was developed in three studies to measure food neophobia (reluctance to eat and avoidance of trying new foods). In Study 1, the original food neophobia scale, FNS (Pliner, & Hobden, 1992), was first critically examined leading to modifications in five and omission of two statements. Furthermore, eight positive and eight negative statements were elicited and introduced along with eight original or modified FNS statements to 575 respondents in South Africa, Lesotho, and Botswana. Study 2 (n = 1010) was used to confirm the factorial structure of the scale, and Study 3 (n = 141) was used to test the reliability of FNS-A through test-retest data. The structure of the scale was analyzed using exploratory (Study 1 and 2) and confirmatory (Study 2) factor analysis, eventually leading to four positive and four negative statements regarding new foods, loaded on two factors labelled approach and avoidance. Test-retest reliability at a 2 weeks' time interval as well as convergent and divergent validity measured against other scales was good (Study 3). In all three studies, predictive validity was evaluated against willingness to try or expected liking ratings of unfamiliar or novel food names or food concept descriptions. This evaluation showed satisfactory performance. FNS-A is a promising tool for the quantification of individual responses to unfamiliar or novel foods, but further studies in other populations and contexts are needed to confirm the applicability.Peer reviewe

Lipofilling in Post-Treatment Oral Dysfunction in Head and Neck Cancer Patients

Lipofilling is a new treatment option for head- and neck cancer patients who suffer from chronic and severe (chemo-) radiation or surgery-related swallowing problems. Lipofilling is a technique of autologous grafting in which living fat cells are transplanted from one location to another in the same patient. In the case of head and neck cancer patients, volume loss or muscle atrophy of the tongue or pharyngeal musculature caused by the treatment may result in oropharyngeal dysfunction. Firstly, intensive swallowing therapy will be given, but if that offers no further improvement and the functional problems persist, lipofilling can be considered. By transplantation of autologous adipose tissue, the functional outcomes might improve by compensating the existing tissue defects or tissue loss. Only a few studies have been published which evaluated the effectiveness of this new treatment option. The results of those studies show that the lipofilling technique seems safe and of potential value for improving swallowing function in some of the included patients with chronic and severe dysphagia after surgery and/or (chemo-) radiation therapy for head and neck cancer. The lipofilling procedure will be described in detail as well as the clinical implications

Galectin-3 negatively regulates the frequency and function of CD4+CD25+Foxp3+ regulatory T cells and influences the course of Leishmania major infection

Galectin-3, an endogenous glycan-binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. However, the role of galectin-3 within the CD4+CD25+Foxp3+ T regulatory (TREG) cell compartment has not yet been explored. Here, we found, in a model of Leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral TREG cells both in draining lymph nodes (LNs) and sites of infection. These observations correlated with an increased severity of the disease, as shown by increased footpad swelling and parasite burden. Galectin-3-deficient (Lgals3−/−) TREG cells displayed higher CD103 expression, showed greater suppressive capacity, and synthesized higher amounts of IL-10 compared with their wild-type (WT) counterpart. Furthermore, both TREG cells and T effector (TEFF) cells from Lgals3−/− mice showed higher expression of Notch1 and the Notch target gene Hes-1. Interestingly, Notch signaling components were also altered in both TREG and TEFF cells from uninfected Lgals3−/− mice. Thus, endogenous galectin-3 regulates the frequency and function of CD4+CD25+Foxp3+ TREG cells and alters the course of L. major infection.Fil: Fermino, Marise L.. Universidade de Sao Paulo; BrasilFil: Dias, Fabrício C.. Universidade de Sao Paulo; BrasilFil: Lopes, Carla D.. Universidade de Sao Paulo; BrasilFil: Souza, Maria A.. Universidade de Sao Paulo; BrasilFil: Cruz, Ângela K.. Universidade de Sao Paulo; BrasilFil: Liu, Fu Tong. University of California at Davis; Estados UnidosFil: Chammas, Roger. Universidade de Sao Paulo; BrasilFil: Roque Barreira, Maria C.. Universidade de Sao Paulo; BrasilFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Bernardes, Emerson S.. Universidade de Sao Paulo; Brasi

Three method factors explaining the low correlations between assessment center dimension ratings and scores on personality inventories

In general, correlations between assessment centre (AC) ratings and personality inventories are low. In this paper, we examine three method factors that may be responsible for these low correlations: differences in (i) rating source (other versus self), (ii) rating domain (general versus specific), and (iii) rating format (multi- versus single item). This study tests whether these three factors diminish correlations between AC exercise ratings and external indicators of similar dimensions. Ratings of personality and performance were combined in an analytical framework following a 2 × 2 × 2 (source, domain, format) completely crossed, within subjects design. Results showed partial support for the influence of each of the three method factors. Implications for future research are discussed. Copyright © 2004 John Wiley & Sons, Ltd

Broad versus narrow traits: Conscientiousness and Honesty-Humility as predictors of academic criteria

Recent research has suggested that the six-dimensional personality model, and especially the dimension Honesty-Humility/Integrity, adds incremental validity to the prediction of important criteria. We expected both this dimension and the dimension Conscientiousness to explain incremental variance in two academic criteria, namely grade point average (GPA) and counterproductive academic behaviour (CAB). In addition, we expected the more specific, so-called narrow traits of Conscientiousness and Honesty-Humility/Integrity to be stronger predictors of academic criteria than the broad traits. To test these expectations, two studies were conducted using the HEXACO Personality Inventory Revised (HEXACO-PI-R) and the Multicultural Personality Test-Big Six (MPT-BS). The results confirmed our expectations and suggest that academic criteria may be predicted with greater accuracy by focusing on the narrow traits of Conscientiousness and Honesty-Humility/Integrity. © 2010 John Wiley & Sons, Ltd