Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.

Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity.

Dose optimization approach to fast X-ray microtomography of the lung alveoli.

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Compatibilidades e incompatibilidades entre radiação gama e óxido de etileno como métodos sucessivos de esterilização

A dúvida sobre a questão da re-esterilização de artigos confeccionados com cloreto de polivinila (PVC), esterilizados em radiação gama (RG) e posteriormente em óxido de etileno (EO) persiste até os dias atuais. Por meio da revisão integrativa da literatura, este artigo analisou estudos que evidenciaram compatibilidades e incompatibilidades entre os processos de esterilização com RG e EO quando utilizados como métodos sucessivos de esterilização. Foram analisados 7 estudos. Constatou-se que há influência multifatorial na segurança do procedimento e que o método analítico da cromatografia empregado na maioria dos estudos produziu resultados controversos. Esse fato indica a necessidade da realização de novos estudos sobre o assunto, utilizando-se métodos analíticos mais sensíveis do que a cromatografia gasosa, como o teste de reatividade biológica em culturas celulares, que poderá dirimir em nosso meio a crônica dúvida da compatibilidade ou incompatibilidade de se esterilizar em EO materiais previamente gamairradiados.

Status of eye lens radiation dose monitoring in European hospitals.

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Randomized controlled trial of olanzapine or chlorpromazine as addition to lithium in the treatment of a first manic episode with psychotic features: an 8-week, flexible dose, single-blind trial

Background: Association of mood stabiliser and antipsychotic medication is indicated in psychotic mania, but specific guidelines for the treatment of a first episode of psychotic mania are needed. Aims: To compare safety and efficacy profiles of chlorpromazine and olanzapine augmentation of lithium treatment in a first episode of psychotic mania. Methods: A total of 83 patients were randomised to either lithium + chlorpromazine or lithium + olanzapine in an 8-week trial. Data was collected on side effects, vital signs and weight modifications, as well as on clinical variables. Results: There were no differences in the safety profiles of both medications, but patients in the olanzapine group were significantly more likely to have reached mania remission criteria after 8 weeks. Mixed effects models repeated measures analysis of variance showed that patients in the olanzapine group reached mania remission significantly earlier than those in the chlorpromazine group. Conclusions: These results suggest that while olanzapine and chlorpromazine have a similar safety profile in a cohort of patients with first episode of psychotic mania, the former has a greater efficacy on manic symptoms. On this basis, it may be a better choice for such conditions.

Eficácia do uso de membrana semipermeável em neonatos pré-termo na redução de perdas transepidérmicas

Neste estudo, investigou-se a eficácia do uso da membrana semipermeável na pele de recém-nascido pré-termo sobre a evolução da perda ponderal e valores da glicemia, cota hídrica, densidade urinária e sódio. Estudo experimental, tipo ensaio clínico randomizado, realizado no período de março a agosto de 2008, na Unidade de Terapia Intensiva Neonatal, de uma maternidade pública, na cidade de Fortaleza-Ceará, Brasil. A amostra foi constituída de 42 recém-nascidos pré-termo. Os dados foram apresentados em tabelas e quadros. Na aplicação da membrana semipermeável, os recém-nascidos pré-termos do Grupo de Intervenção tiveram uma diminuição de níveis de sódio e de exigências fluidas diárias, como também apresentaram menores episódios de hiperglicemia e a densidade urinária foi mantida dentro dos padrões de normalidade. A membrana semipermeável é, de fato, um recurso terapêutico eficaz para minimizar as perdas de água transepidérmicas.

Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis.

Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against small amounts of inocula. Clarithromycin may be considered for endocarditis chemoprophylaxis in human.

Optimisation des doses en tomographie computérisée pédiatrique [Patient dose optimization in pediatric computerized tomography]

The development of CT applications might become a public health problem if no effort is made on the justification and the optimisation of the examinations. This paper presents some hints to assure that the risk-benefit compromise remains in favour of the patient, especially when one deals with the examinations of young patients. In this context a particular attention has to be made on the justification of the examination. When performing the acquisition one needs to optimise the extension of the volume investigated together with the number of acquisition sequences used. Finally, the use of automatic exposure systems, now available on all the units, and the use of the Diagnostic Reference Levels (DRL) should allow help radiologists to control the exposure of their patients.

Eficácia da auriculoterapia na redução de ansiedade em estudantes de enfermagem

Este Ensaio Clínico Randomizado simples-cego verificou níveis de ansiedade dos estudantes de Enfermagem de nível médio da Escola de Enfermagem São Joaquim, do Hospital Beneficência Portuguesa, e a eficácia da auriculoterapia na redução desses níveis. Foi aplicado o Inventário de Ansiedade Traço-Estado no início, após 8 e 12 sessões e no follow-up (quinze dias). A amostra foi composta por 71 indivíduos divididos em três grupos: Controle sem intervenção (25), Auriculoterapia (24), e Placebo (22). Resultados: Na análise de variância (ANOVA) houve diferença estatisticamente significativa pelo Post Hoc entre os grupos controle/auriculoterapia na segunda (p=0.000), terceira (p=0.012) e quarta avaliações (p=0.005); e entre grupos placebo/controle, somente na 2ª avaliação (p=0.003). A auriculoterapia com os pontos Shenmen e Tronco Cerebral foi mais eficaz para a diminuição dos níveis de ansiedade em estudantes de Enfermagem (20,97%), em comparação com os pontos sham (13,74%), porém, estudos com amostragem mais representativa se fazem necessários.

Enfermagem transoperatória nas cirurgias de redução de peso: revisão integrativa da literatura

Estudo de revisão integrativa da literatura científica com a finalidade de identificar e analisar a produção de conhecimento sobre avanços clínicos em necessidades de segurança de pacientes no período transoperatório de cirurgia bariátrica, baseada em 12 estudos selecionados em bases eletrônicas, a partir de descritores previamente definidos. Com exceção de dois estudos, o conteúdo específico dessa produção compunha o contexto geral da assistência perioperatória. A análise dos estudos possibilitou evidenciar o estado da arte da atuação da enfermagem sobre essas necessidades, as quais já estão bem estabelecidas, inclusive por vários guias de recomendações, contudo, fundamentalmente baseadas na ciência da prática clínica tradicional, por meio da elaboração de juízos racionais teóricos de especialistas. Conclui-se pela pertinência de realização de estudos primários para avaliar, principalmente, impacto e resolutividade dos recursos identificados para atendimento dessas necessidades, assim como melhoria ou geração de outros recursos inovadores e identificação de novas necessidades.

Citotoxicidade de tubos de PVC esterilizados em óxido de etileno após exposição à radiação gama

Materiais esterilizados em raios gama, ao serem re-esterilizados em óxido de etileno (EO), formam substâncias tóxicas? Esta questão norteou o objetivo deste estudo, que foi investigar o potencial efeito citotóxico do PVC esterilizado em radiação gama e re-esterilizado em EO pelo método da difusão em ágar em culturas celulares. Nove tubos de PVC foram submetidos à esterilização em radiação gama e re-esterilizados em EO. Os tubos foram divididos em um total de 81 unidades de análise, que foram testadas de forma a representar as superfícies internas, externas e massa de cada tubo. Concluiu-se que os materiais de PVC esterilizados em Radiação Gama e consecutivamente re-esterilizados em EO não são citotóxicos.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.