Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX (TM) adjuvant in women with cervical intraepithelial neoplasia

Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia

Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and Pan IN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early Pan IN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer

The development of colorectal cancer is a major complication for patients with chronic idiopathic colitis. Colitis-associated tumours tend to occur at a younger age and be more aggressive than sporadic colorectal cancers. While we have previously associated the presence of tumour-infiltrating lymphocytes (TILs) and increased apoptosis in sporadic colorectal cancer with high-level microsatellite instability and improved prognosis, little is known of the relationship between these variables in colitis-associated colorectal cancer. The aim of this study was to correlate TILs and tumour cell apoptosis in colitis-associated neoplasms stratified according to microsatellite instability. Twenty tumour and 11 dysplastic samples resected from 21 patients with long-standing colitis were analysed for microsatellite instability at 10 microsatellite markers. TIL distribution (CD3, CD8) and function (granzyme B) were quantified by immunohistochemistry. Neoplastic cell apoptosis was assessed using the M30 CytoDEATH antibody. These findings were compared with 40 microsatellite stable (MSS) sporadic colorectal cancers previously evaluated for TILs and neoplastic apoptosis. Low-level microsatellite instability was found in 1/20 colitis-associated tumours. All other colitis-associated lesions were designated MSS. CD3(+) and CD8(+) TIL counts were significantly higher in colitis-associated lesions compared with NISS sporadic colorectal cancer (p < 0.0001, p = 0.001 respectively). Despite their higher TIL density, colitis-associated tumours were more likely to present late (Dukes' stage C or D) (P = 0.02). Functionally, colitis-associated TILs demonstrated significantly less granzyme B expression compared to sporadic cancers (p = 0.002). The level of tumour cell apoptosis was similar between the two groups (sporadic, 1.53%; colitis cancers, 1.45%). In conclusion, NISS colitis-associated tumours have a higher prevalence of CD3(+)/CD8(+) TILs but no associated increase in tumour cell killing by apoptosis. Unlike cytotoxic T cells in sporadic colorectal cancer, TILs do not appear to enhance the prognosis of colitis-associated colorectal cancer. This may be related to an impairment of granzyme B expression within these lesions. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.

Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia

Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/ subcutaneous head and trunk. Stage la was the most common tumour stage at first diagnosis (n = 20), followed by stage 4 (both stage 4a and stage 4b; n = 10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n = 30) and those with tumours involving the spleen or lymph nodes (n = 11) showed longer survival times for the cutaneous-only group (P = 0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n = 6) or a single tumour (n = 19), cats with single tumours survived longer than those with multiple tumours (P = 0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. (C) 2006 ESFM and AAFR Published by Elsevier Ltd. All rights reserved.

New era: Prophylactic surgery for patients with multiple endocrine neoplasia-2A

Background: The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation. Method: This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older. Results: There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma. Conclusion: Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or 'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.

DIVERGÊNCIAS E CONVERGÊNCIAS ENTRE A COMUNICAÇÃO PRIMÁRIA E A COMUNICAÇÃO SECUNDÁRIA NA DIVULGAÇÃO DO CÂNCER DE MAMA

Este estudo investiga as convergências e as divergências na comunicação primária e na comunicação secundária do câncer de mama. Nós usamos um esquema interpretativo fornecido pela Análise de Enquadramento, Agenda Setting, Teoria do Aprendizado Social, Difusão de Inovações, Semiótica e conceito de Novidade na Ciência e no Jornalismo, para argumentar que cientistas e jornalistas comunicam as novidades da Ciência de modos diversos. Também tivemos como uma proposta secundária traçar um panorama histórico da Comunicação da Saúde, e sua evolução, considerando que a Comunicação empreendeu um esforço para legitimar um espaço de encontro com a Saúde, afirmando uma área de aplicação de teorias, princípios e técnicas comunicacionais, com o objetivo preciso de difundir e compartilhar informação, conhecimentos e práticas que contribuam para melhorar os sistemas de saúde e o bem-estar das populações. Através da análise dos dados de periódicos científicos e jornalísticos que divulgam o câncer de mama, nós encontramos apoio significante para nossas predições. As implicações destas diferenças entre a comunicação primária (interpares) e a comunicação secundária (público leigo) para a comunicação da saúde são discutidas, às vezes apresentando-se como convergências, às vezes como divergências. Quando bem esclarecidas e compreendidas, fazem avançar a Comunicação da Saúde, obtendo resultados positivos no bem-estar das populações, considerando que a origem das doen ças está, fundamentalmente, onde se entrelaçam o biológico e o social.(AU)

Avaliação do pré-natal na atenção primária à saúde no Rio grande do Norte: visão das usuárias

ABSTRACT This study aimed to evaluate the quality of prenatal Primary Care in Rio G rande do Norte, Brazil in 2012 under the program Improving Access and Quality of Primary Care. The study was cross - sectional, quantitative. Included 156 mothers of children under 2 years who received prenatal care at the health evaluated. We applied a ques tionnaire on profile, minimum queries, regularity of attendance, laboratory tests, vaccination, participation in educational activities, guidance received, clinical and obstetric procedures and prescription Ferrous sulphate and folic acid. The descriptive analysis of the criteria used Humanization Program Prenatal and Birth. The results showed that 92% of mothers had six or more visits; 85% with the same care was professional; 94% subsequent appointments scheduled. As for tests and procedures the percentage s were: Urine 98%; HIV - 96%; VDRL and 88%; 91% glucose; tetanus vaccination 93%; educational groups 56% with 36% participation, knowledge of the delivery location and 59% achievement breast exam 65%, 33% and preventive gynecological 43%; 98% supplemented wi th 96% Ferrous Sulfate and Folic Acid. It was concluded that there were advances in Rio Grande do Norte concerning assistance and there are weaknesses in the educational practices and conducting some minimal clinical examinations.

A prática do enfermeiro da atenção primária à saúde nas consultas ao paciente com tuberculose

This study aimed to analyze the practice of nurses regarding the development of the nursing process in the consultation to the patient with tuberculosis. This is a descriptive study with quantitative approach, performed with 60 nurses of the Primary units of the city of Natal, RN Health. The project was approved by the Ethics Committee of the Federal University of Rio Grande do Norte. To collect data, we used a structured questionnaire, developed from the "Consultation of Nursing," the Nursing Protocol for the Treatment of Tuberculosis Directly Observed in Primary Care, Ministry of Health. The instrument was subjected to pre- -test and contained questions regarding the elements used by the nurse in consultation with the patient with tuberculosis and an open question about the feasibility of implementing the Nursing Process in Primary Health Care. data collection was conducted between September and October 2014, in health units work of each participant. Data were analyzed using SPSS 20. The answers to the open question were analyzed for themes and quantified for analysis. With respect to the elements of nursing process used in consultation with the patient with tuberculosis, were on the history of nursing at the expense of survey nursing diagnosis, action planning, implementation and evaluation. Step in the history of nursing, however, the actions were toward complaints and symptoms of the disease (100% of the nurses always investigating). Social and cultural aspects involved in for tuberculosis, as stigma and difficulties in routine work, were less addressed by nurses (43.3% never investigated suffering stigma; 46.7% sometimes investigating changes in the work routine patient ). The physical examination was focused on measuring patient weight (100% held). To the understanding of nurses on the implementation of the nursing process Primary Health Care, favorable factors were identified, such as that this implementation can promote greater scientific basis for nursing (36.7%); and hindering aspects, such as the understanding that Primary Health Care is pervaded by bureaucratic issues and high demand (13.3%). Be established in consultation with the nurse fragmentations, since elements as identification of nursing diagnoses, action planning and evaluation were not made in full by the professionals. Highlights the need for continuing education for nurses who are included in Primary Health Care, seeking to maximize the autonomy of these professionals in developing a practice grounded in scientific knowledge

Travestis na atenção primária: o cuidado em saúde na cidade de Natal

Among the deviant a heteronormative ideal, transvestites are the ones that suffer abuse and discrimination. Have been found that health services often present themselves as places that maintains and reproduce such discrimination, which makes transvestites only sought medical care in the latter case. Based on the guidelines of the SUS and the National Humanization Policy as well as the inclusion and leadership of the users, we conducted a qualitative study seeking to understand the experience of transvestites in seeking health care within primary care in Natal-RN. We use as techno-methodological instruments in depth interview and workshop with use of "scenes". For interpretative analysis of the narratives we use to Hermeneutics-Dialectic. From the dialogue with the narrative we come to the following themes: 1) Understanding the meaning of being a transvestite; 2) The experience transvestite in search of health; 3) Transvestites and humanized health care. In the first point they reveal the daily struggle of transvestites between prejudice and the search for respect, as well as the meanings of being a transvestite, who appeared as: Being gay, being feminine, not transsexual and accept themselves as they are. In the second axis, expressed difficulties in access to and use of health services: the embarrassment by not using the social name; fear of going out during the day; the association of transvestites to HIV; and pain caused by discrimination from health professionals. It was also possible to identify simple demands such as illnesses from day to day, the demand for hormone therapy, which involves treatment needs as well as the vital need to have their rights XVII respected. The third axis, for the range of a humanized care identified that the respectful gaze guarantee their dignity and their right to health in a humane way, but it identified some necessary changes: Training of professionals, dialogue with the social movement, publicity campaigns and rapprochement with the transvestite. Finally, it is expected that the research will contribute to the field of knowledge know-how in health care transvestites, inside and outside of the university

O trabalho em equipe na atenção primária à saúde: situação de Portugal e do Brasil

Introdução: Na Atenção Primária à Saúde, nos contextos internacional e nacional, o trabalho em equipe tem sido reconhecido como estratégia decisiva para a organização de processos que visam à integralidade do cuidado, além de possibilitar melhorias na satisfação dos usuários com os serviços de saúde. Neste sentido, o objetivo, deste estudo, é analisar o trabalho em equipe na Atenção Primária à Saúde. Método: Trata-se de uma pesquisa em banco de dados secundários. Realizou-se três estudos: a) O trabalho em equipe na Atenção Primária à Saúde, em Portugal, pesquisa avaliativa, de natureza qualitativa, tipo estudo de caso descritivo, que representou um recorte dos resultados derivados da pesquisa integrada ao projeto “Implantação das Unidades de Saúde Familiar em Portugal”, que teve como procedimentos entrevistas semiestruturadas, roteiro de coleta de informações (check list) e análise documental. Foi realizada a estratégia de triangulação dos dados com análise de conteúdo; b) trabalho em equipe, acesso e qualidade na Atenção Primária à Saúde, no Brasil, estudo transversal, de abordagem quantitativa, realizado a partir dos dados obtidos da “Pesquisa de Avaliação Externa do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica”, no Brasil, em 2013. Amostra composta de 17202 profissionais e 65391 usuários. Utilizou-se entrevista estruturada, com análise estatística realizada pelas frequências absolutas e relativas das variáveis através do programa Statistical Package for Social Sciences. c) satisfação dos usuários com o trabalho em equipe na Atenção Primária à Saúde, no Brasil, estudo transversal, de abordagem quantitativa, realizado a partir dos dados obtidos da “Pesquisa de Avaliação Externa do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica”, no Brasil, em 2013. Amostra composta de 65391 usuários. Realizou-se análise estatística das frequências absolutas e relativas das variáveis através do programa Statistical Package for Social Sciences. Utilizou-se, ainda, o Teste X2 , com nível de significância de 5%; análise de regressão logística múltipla. O modelo final foi ajustado pelo teste de Hosmer/Lemeshow, o qual indicou um ajuste de 66%. Resultados: Sobre o trabalho em equipe na Atenção Primária à Saúde, em Portugal, destacou-se a formação das equipes de forma voluntária, por meio de afinidades pessoais, a existência de “carteira básica de serviços”, juntamente com x intervenções de vigilância, promoção da saúde e prevenção de doença, cuidados em situação de doença aguda, acompanhamento clínico de doença crônica e de patologia múltipla, cuidados domiciliares, interligação e colaboração em rede com outros serviços (cuidados hospitalares), sistemas informatizados nas unidades de saúde. Os dados revelaram dificuldades quanto ao atendimento domiciliar. No Brasil, foi destaque o processo de trabalho, com avanços relacionados a realização de planejamento e programação das ações e o apoio da gestão. Existência de território definido e de prontuários familiares. É destaque a agenda compartilhada e pactuada entre os profissionais. As equipes realizam acolhimento e reuniões, cujos temas, discutidos, giram em torno do processo de trabalho e planejamento. Os desafios, enfrentados, estão relacionados ao agendamento dos usuários; ao número de pessoas sob a responsabilidade das equipes; à existência de população descoberta nas áreas adscritas à Unidade de Saúde; à incipiência na ação intersetorial e ao pouco envolvimento da comunidade pelas equipes. Quanto aos fatores associados à satisfação do usuário foi marcante: a faixa etária; a escolaridade; a raça; se a falta de material prejudica o atendimento e se a equipe consegue marcar consulta para outros profissionais. Conclusões: Constatou-se o trabalho em equipe como elemento central no processo de mudança na Atenção Primária à Saúde, tanto no contexto de Portugal quanto no do Brasil, o qual ampliou o acesso e a qualidade na oferta de serviços de saúde e obteve, ainda, o reconhecimento social, mesmo que, em ambas as realidades, não tenha avançado na coordenação do cuidado e no estímulo à participação social. Os fatores, associados com a satisfação do usuário, estão relacionados diretamente ao cuidado prestado e refletem a expectativa, por parte do usuário, de resolução concreta de suas necessidades.

História oral de vida de pessoas com úlcera venosa nos serviços de atenção primária à saúde

The Chronic Venous insufficiency is characterized as a set of physical changes including how most serious complication of venous ulcers, characterized by irregular and progressive loss of continuity of the skin. The occurrence of venous ulcers in people with chronic venous insufficiency generates dependence on them with health services, with long-term treatments that cause limitations and high-impact changes, affecting their quality of life, affecting the physical, psychological, social, cultural and spiritual as an important public health problem. This study aimed to describe the experience of having a venous ulcer, in the scenario of primary health care services to Health, which includes Primary Care Units and Family Health Strategy in the city of Natal / RN, based on the life histories of users. This is a qualitative study, exploratory and descriptive, with the Oral History of Life as a methodological framework. From the ponto zero was the recruitment of participants who formed the network, totaling six employees, of both sexes and aged between 57 and 79 years. After approval by the Research Ethics Committee - UFRN under the Protocol 653 788/2014 and CAAE 30408014.0.0000.5537 was held data collection, between the months of July and August, through interviews, using identification and characterization of the instrument employees and open questions. Interviews were recorded, transcribed, transcriadas and returned to employees for a conference. The narratives were subjected to Content thematic analysis technique, according to Bardin, allowing the construction of three themes that encompass categories, namely: Axis I - Perspectives on the changes: the impact wound in social relations (changes with ulcer venous, venous ulcer and social and family relationships); Axis II - Brands in body and soul: the story of being hurt (conceptions of the body injured; therapeutic itinerary in primary care services); and Axis III - Reconstruction of being hurt: coping mechanisms (redefinition of the wounded body, resilience to chronic wound). The impact of having a chronic venous ulcer generates impact of physical, psychological and social order. As aspects related to changes after the appearance of venous ulcers, survey participants reported the presence of pain, physical limitations, psychological distress, social and emotional isolation, incapacity, aesthetic discomfort and dependency on health services; the family was the aspect thatshowed no significant change after the occurrence of wound for most participants, an ally in the therapeutic process as a support network. The redefinition of the body and the wound are the main coping mechanism of chronic condition. The services in the Primary Care Network play a fundamental role in the rehabilitation of patients with venous ulcers, although there are difficulties in accessing appropriate treatment and need for expanded services, with permanent professional training of health teams and providing the resources managers to strengthen the comprehensive care of people with venous ulcers in Health Primary Care.