Valor da calprotectina fecal na determinação da actividade da doença inflamatória intestinal : ênfase particular na recidiva pós-cirúrgica nos doentes com doença de Crohn

Trabalho de projecto de mestrado em Medicina, apresentado à Faculdade de Medicina da Universidade de CoimbraA Doença Inflamatória Intestinal (DII) é uma doença crónica, cursando com períodos de remissão e de agudização. Vários métodos podem ser utilizados na avaliação da sua actividade mas aqueles que são utilizados na prática clínica têm baixa especificidade e sensibilidade ou são de carácter invasivo. Assim torna-se facilmente compreensível que se insista na necessidade de encontrar alternativas que idealmente deverão caracterizar-se por serem de fácil utilização, terem um carácter não invasivo e apresentarem custos reduzidos. A terapêutica médica da DII consiste na diminuição da inflamação, quer pela imunomodulação, quer pela imunossupressão, tornando por isso, imprescindível a quantificação da inflamação activa para aferição terapêutica. Os índices clínicos, embora importantes, são facilmente influenciáveis por fenómenos não inflamatórios (estenoses, fístulas e procedimentos cirúrgicos); os marcadores séricos (velocidade de sedimentação e proteína C reactiva) apresentam baixa acuidade decorrente em grande parte da ausência de sensibilidade e especificidade para a inflamação intestinal. A colonoscopia com biopsias (considerado o método gold standard para avaliação da actividade da doença) e a cápsula endoscópica são exames invasivos e dispendiosos. A calprotectina é uma proteína ligada ao cálcio derivada predominantemente dos neutrófilos, constituindo mais de 60% das proteínas do citosol. Desta forma, a sua presença nas fezes é proporcional à migração neutrofílica através do tracto gastrointestinal e consequentemente ao grau de inflamação da parede do tubo digestivo. Para além disso, apresenta estabilidade nas fezes à temperatura ambiente, resistência à actividade de degradação pelas bactérias intestinais e pode ser quantificada por ELISA, características estas que a tornam atractiva para a prática clínica. A concentração da calprotectina fecal (CF) é proporcional à inflamação intestinal: quando aumentada é preditiva de inflamação severa ao exame anatomo-patológico. Admite-se assim a hipótese de, numa condição patológica caracterizada pela oscilação entre períodos de actividade e sendo a recorrência endoscópica mais precoce que a clínica, que a CF terá a capacidade de predizer recidivas clínicas em doentes assintomáticos, reduzindo assim a necessidade de explorações endoscópicas durante tratamento. Particularizando, na Doença de Crohn (DC), a cirurgia não é curativa pelo que o risco de recorrência pós-cirúrgica é grande. Desta forma, a instituição de terapêutica profilática está dependente da avaliação objectiva da actividade da doença, nomeadamente o estudo endoscópico capaz de detectar lesões macroscópicas tradutoras de recidiva clínica. O Score de Rutgeerts é o utilizado na mensuração e uniformização destes achados em doentes com DC já submetidos a uma ressecção íleo-cólica. Pretende-se assim analisar a capacidade do doseamento da CF como meio complementar de diagnóstico não invasivo na predicção de recidiva da DC. A aluna propõe-se estudar prospectivamente 30 doentes com diagnóstico de Doença de Crohn já submetidos a ressecção ileo-cecal, assintomáticos (Crohn´s Disease Activity Índex<150) e com terapêutica estável nas últimas 12 semanas. Os valores de CF serão comparados com os achados endoscópicos, classificados de acordo com índice de Rutgeerts e secundariamente, a CF será comparada também com os valores laboratoriais (hemoglobina, leucócitos, plaquetas e proteína C reactiva). Desta forma, pretende-se determinar a acuidade da CF no diagnóstico de recidiva endoscópica (definida no material e métodos) utilizando o valor de cut-off recomendado. Para alem disso, pretende-se determinar um novo cut-off com maior sensibilidade e especificidade e verificar a existência de correlação entre os valores de CF, índice endoscópico e parâmetros analíticos.Inflammatory bowel disease (IBD) is a chronic condition marked by recurrent episodes of inflammation. Several methods may be used for the assessment of its activity but they have either low specificity or are invasive procedures. Although its easily understandable that all the efforts may be made to identify alternative methods, ideally simple to use, non invasive and affordable. The objective of medical therapy in IBD is to reduce inflammation by its immunomodulation or immunosuppressive actions, hence the need of quantifying inflammation for the assessment of the therapeutic effect. The clinical scores, although relevant, are easily influenced by non-inflammatory issues (such as stenosis, fistulization and surgical procedures), serologic markers (erythrocyte sedimentation rate and reactive C protein) have low diagnostic accuracy because of its low sensitivity and specificity. Colonoscopy with biopsies (considered the gold standard method in the evaluation in the disease activity) and capsule endoscopy are invasive and expensive procedures. Calprotectin is a calcium-binding protein that is derived predominantly from neutrophils, adding up to 60% of the cytosolic proteins from granulocytes. Consequently the presence of calprotectin in feces is directly proportional to neutrophil migration to the intestinal tract and its inflammation degree. Calprotectin has excellent stability in feces at room temperature, is resistant to intestinal bacterial degradation and is quantifyed by ELISA testing, making it an attractive option in daily practice. Fecal calprotectin (FC) is proportional to the inflammation in the intestinal tract, hence, when increased is predictive of severe inflammation at endoscopic and histological study. With that basis we admitted that in a condition that curses with flares and periods without clinical symptoms, and considering that endoscopic relapse occurs previous to clinical symptoms, FC has the capability to predict relapses in asymptomatic patients, reducing the need for endoscopic evaluation during the therapy. Especially in CD, surgery is no curative and the risk of recurrence is high. So, the institution of prophylactic therapy is dependent of the measurement of its activity, namely with endoscopic study by identifying macroscopic lesions compatible with relapse. Rutgeerts score is used in the standardization of these findings in CD patient’s prior submitted to ileocolonic resection. The aim is to analyze FC as a non-invasive procedure in predicting CD relapses. The author proposes to study prospectively 30 patients with de CD diagnosis, previously submitted to ileocolonic resection, asymptomatic (defined with a CDAI<150) on stable therapy by the last 12 weeks. The FC values will be compared with the endoscopic findings (defined with the Rutgeetrs score) and, as secondary analysis, FC values will be compared with serologic values (namely hemoglobin, leucocytes, platelets and reactive C protein). The main goal is to determine CF accuracy in the diagnosis of endoscopic relapse, firstly using the cut-off proposed by the manufacturer and secondly calculating a new one with increased sensibility and specificity. The relation of FC levels with the other evaluated laboratory marker will also de reviewed

Computerised tomography and magnetic resonance imaging of laryngeal squamous cell carcinoma: A practical approach

Squamous cell carcinoma is the most common head and neck cancer. This review describes the state-of-the-art computerised tomography and magnetic resonance imaging protocols of the neck and the normal larynx anatomy, and provides a practical approach for the diagnosis and staging of laryngeal squamous cell carcinoma

Solar wind interaction with comet 67P: impacts of corotating interaction regions

International audienceWe present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1–2.7 AU from the Sun and the neutral outgassing rate ∼1025–1026 s−1, the CIRs significantly influence the cometary plasma environment at altitudes down to 10–30 km. The ionospheric low-energy (∼5 eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below −20 V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (∼10–100 eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2–5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events

Spatial distribution of low-energy plasma around 2 comet 67P/CG from Rosetta measurements

International audienceWe use measurements from the Rosetta plasma consortium (RPC) Langmuir probe (LAP) and mutual impedance probe (MIP) to study the spatial distribution of low-energy plasma in the near-nucleus coma of comet 67P/Churyumov-Gerasimenko. The spatial distribution is highly structured with the highest density in the summer hemisphere and above the region connecting the two main lobes of the comet, i.e. the neck region. There is a clear correlation with the neutral density and the plasma to neutral density ratio is found to be ∼1-2·10 −6 , at a cometocentric distance of 10 km and at 3.1 AU from the sun. A clear 6.2 h modulation of the plasma is seen as the neck is exposed twice per rotation. The electron density of the collisonless plasma within 260 km from the nucleus falls of with radial distance as ∼1/r. The spatial structure indicates that local ionization of neutral gas is the dominant source of low-energy plasma around the comet

Simple and fast orotracheal intubation procedure in rat

Introduction: Endotracheal intubation in the rat is difficult because of extremely small size of anatomical structures (oral cavity, epiglottis and vocal cords), small inlet for an endotracheal tube and the lack of proper techniacal instruments. Matherial and Methods: In this study we used seventy rats weighthing 400-500 g. The equipment needed for intubation was an operating table, a longish of cotton, a cotton tip, orotracheal tube, neonatal laryngoscope KTR4, small animal ventilator, and isoflurane for inhalation anaesthesia. Premedication was carried out by medetomidine hydrochloride 1 mg/mL; then, thanks to a closed glass chamber, a mixture of oxygen and isoflurane was administered. By means of neonatal laryngoscope the orotracheal tube was advanced into the oral cavity untile the wire guide was visualized trough the vocal cords; then it was passed through them. The tube was introduced directly into into the larynx over the wire guide; successively, the guide was removed and the tube placed into the trachea. Breathing was confirmed using a glove, cut at the end of a finger, simulating a small ballon. Conclusions: We believe that our procedure is easier and faster than those previously reported in scientific literature. (www.actabiomedica.it