The role of endothelial enzymes NOS, VAP-1 and CD73 in acute lung injury

Acute lung injury (ALI) is a syndrome of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that is not caused by left atrial hypertension. Since there is no effective treatment available, this frequent clinical syndrome significantly contributes to mortality of both medical and surgical patients. Great majority of the patients with the syndrome suffers from indirect ALI caused by systemic inflammatory response syndrome (SIRS). Sepsis, trauma, major surgery and severe burns, which represent the most common triggers of SIRS, often induce an overwhelming inflammatory reaction leading to dysfunction of several vital organs. Studies of indirect ALI due to SIRS revealed that respiratory dysfunction results from increased permeability of endothelium. Disruption of endothelial barrier allows extravasation of protein-rich liquid and neutrophils to pulmonary parenchyma. Both under normal conditions and in inflammation, endothelial barrier function is regulated by numerous mechanisms. Endothelial enzymes represent one of the critical control points of vascular permeability and leukocyte trafficking. Some endothelial enzymes prevent disruption of endothelial barrier by production of anti-inflammatory substances. For instance, nitric oxide synthase (NOS) down-regulates leukocyte extravasation in inflammation by generation of nitric oxide. CD73 decreases vascular leakage and neutrophil emigration to inflamed tissues by generation of adenosine. On the other hand, vascular adhesion protein-1 (VAP-1) mediates leukocyte trafficking to the sites of inflammation both by generation of pro-inflammatory substances and by physically acting as an adhesion molecule. The aims of this study were to define the role of endothelial enzymes NOS, CD73 and VAP-1 in acute lung injury. Our data suggest that increasing substrate availability for NOS reduces both lung edema and neutrophil infiltration and this effect is not enhanced by concomitant administration of antioxidants. CD73 protects from vascular leakage in ALI and its up-regulation by interferon-β represents a novel therapeutic strategy for treatment of this syndrome. Enzymatic activity of VAP-1 mediates neutrophil infiltration in ALI and its inhibition represents an attractive approach to treat ALI.

Apolipoprotein E and Recovery from Traumatic Brain Injury

The outcome from traumatic brain injury (TBI) is variable and only partly explained by known prognostic factors. This is especially true for predicting long-term outcome. Genetic factors may influence the brain`s susceptibility to injury or capacity for repair and regeneration. To examine the association of apolipoproteinE (apoE) genotype with long-term outcome, hippocampal volumes and general brain atrophy, we determined the apoE genotype from 61 TBI patients who had been injured over on average 31 years earlier. The long-term outcome was evaluated with repeated neuropsychological testing and by applying various measures of everyday functioning and quality of life. Magnetic resonance imaging (MRI) based volumetric analyses of the hippocampus and lateral ventricles were performed. In the prospective study, the purpose was to examine the association between apoE genotype and visibility of traumatic brain lesions during the first year after TBI and the ability of apoE genotype, the Glasgow Coma Score (GCS), MRI findings and duration of posttraumatic amnesia (PTA) to predict the one-year outcome. Thirty-three patients with TBI were studied and the outcome was evaluated with the Head Injury Symptom Checklist (HISC) and the Glasgow Outcome Scale extended version (GOS-E) scores one year after the injury. MRI and apoE genotyping were carried out. After three decades, neither hippocampal nor lateral ventricle volumes differed significantly in those patients with the apoE ε4 allele vs those without this allele, but the TBI patients with the apoE ε4 allele showed significantly poorer general cognitive level than those without this allele. This decline was wholly accounted for by a subgroup of patients who had developed incident or clinical dementia. In the prospective study the apoE genotype was not associated with visible MRI changes or outcome. The duration of PTA and acute MRI were the best predictors of one-year outcome in TBI. A portion of the TBI patients with the apoE ε4 allele seem to be at risk of long-term cognitive decline. This association may involve mechanisms other than those responsible for the development of brain atrophy. The early MRI and PTA have an important role in assessing the injury severity and prognosis.

Determinants of the decision to appeal against motor bodily injury settlements awarded by Spanish trial courts

Automobile bodily injury disputes represent one of the main causes of litigation faced by Spanish Courts. In this paper a multinomial model is implemented to analyse which factors determine the decision to appeal against the verdicts of trial courts. Use of a dataset of motor insurance claims revealed differences between the determinants of a claimant’s decision to appeal and those of insurers. Among other results it is shown that discrepancies regarding the permanent disability sustained affect the insurer’s decision to appeal. In contrast, the claimant pays more attention to differences in the stated temporary disability. Conclusions are drawn regarding which factors could reduce the percentage of appealed cases.

Speaking Wounds – Silence, Self-injury and Healing in Patricia McCormick‟s Cut

Pro gradu -tutkielmani käsittelee itsensä vahingoittamisen, hiljaisuuden ja toipumisen representaatioita Patricia McCormickin nuorille aikuisille suunnatussa teoksessa Cut. Tutkielman tarkoituksena on analysoida itsensä vahingoittamista kirjallisuudentutkimuksellisesta näkökulmasta. Vaikka itsensä vahingoittamisesta on englanninkielisillä markkinoilla olemassa runsaasti psykologista kirjallisuutta, ei sen representaatioita kirjallisuudessa ole vielä juurikaan tutkittu. Näiden representaatioiden analysointi on tärkeää, sillä 1990-luvun alkupuolella syntyi nuortenkirjallisuudessa genre, joka keskittyy juuri itsensä vahingoittamisen käsittelyyn. Patricia McCormickin Cut on edustava esimerkki tämän genren romaanista. Tutkimuksen teoreettinen viitekehys koostuu monitieteellisistä teksteistä. Ensisijaisina lähteinä ovat Patrick Fueryn teoreettiset käsitykset hiljaisuudesta ja poissa-olosta sekä Christine Wilkie-Stibbsin feministiset luennat yksittäisistä nuortenkirjoista. Armando R. Favazzan kliiniset määritelmät itsensä vahingoittamisesta luovat perustan käyttämilleni termeille. Pääpaino tutkielmassa on kuitenkin omalla luennallani romaanista. Tutkimustuloksena on, että sekä päähenkilön hiljaisuus että itsensä viiltely ovat monimerkityksisiä ja dynaamisia tiloja. Ne toimivat kommunikaation ja itsehoidon välineinä. Viiltelyyn sisältyy voimakkaasti hoivan käsite, sillä viiltämällä itseään päähenkilö yrittää käsitellä ja helpottaa henkistä ahdistustaan. Sekä hiljaisuus että viiltely auttavat eri tavoin päähenkilöä käsittelemään ja sisäistämään oman tilansa ja näin ollen myös edistävät paranemisprosessia, joka jatkuu puheen kautta perinteisessä psykoterapeuttisessa diskurssissa. Teos painottaa puheen roolia, mutta myös hiljaisuus ja viiltely muodostavat yhtäläiset kommunikaatio- ja hoitoväylät.

Eye Fundus Image Analysis for Automatic Detection of Diabetic Retinopathy

Diabetes is a rapidly increasing worldwide problem which is characterised by defective metabolism of glucose that causes long-term dysfunction and failure of various organs. The most common complication of diabetes is diabetic retinopathy (DR), which is one of the primary causes of blindness and visual impairment in adults. The rapid increase of diabetes pushes the limits of the current DR screening capabilities for which the digital imaging of the eye fundus (retinal imaging), and automatic or semi-automatic image analysis algorithms provide a potential solution. In this work, the use of colour in the detection of diabetic retinopathy is statistically studied using a supervised algorithm based on one-class classification and Gaussian mixture model estimation. The presented algorithm distinguishes a certain diabetic lesion type from all other possible objects in eye fundus images by only estimating the probability density function of that certain lesion type. For the training and ground truth estimation, the algorithm combines manual annotations of several experts for which the best practices were experimentally selected. By assessing the algorithm’s performance while conducting experiments with the colour space selection, both illuminance and colour correction, and background class information, the use of colour in the detection of diabetic retinopathy was quantitatively evaluated. Another contribution of this work is the benchmarking framework for eye fundus image analysis algorithms needed for the development of the automatic DR detection algorithms. The benchmarking framework provides guidelines on how to construct a benchmarking database that comprises true patient images, ground truth, and an evaluation protocol. The evaluation is based on the standard receiver operating characteristics analysis and it follows the medical practice in the decision making providing protocols for image- and pixel-based evaluations. During the work, two public medical image databases with ground truth were published: DIARETDB0 and DIARETDB1. The framework, DR databases and the final algorithm, are made public in the web to set the baseline results for automatic detection of diabetic retinopathy. Although deviating from the general context of the thesis, a simple and effective optic disc localisation method is presented. The optic disc localisation is discussed, since normal eye fundus structures are fundamental in the characterisation of DR.

A Tomada de Decisão (Bio)ética: Estudo Preliminar Utilizando o Mobile Eye Tracking

RESUMO A tomada de decisão é uma das dimensões essenciais da formação do profissional da saúde, como mencionado nas atuais Diretrizes Curriculares Nacionais do Curso de Graduação em Medicina. O processo decisório, no âmbito da saúde, envolve diferentes aspectos, incluindo os elementos (bio)éticos. Nesse sentido, pesquisas que investiguem a tomada de decisão em (bio)ética poderão elucidar passos ainda não completamente esclarecidos, permitindo uma construção mais efetiva das competências em (bio)ética, na graduação e na pós-graduação. Diante desta perspectiva, o objetivo deste estudo é explorar possibilidades de uso do Mobile Eye Tracking para o estudo do papel da atenção visual – durante a exibição de filmes de cinema – no processo decisório em (bio)ética.

Reading Development During Elementary School Years. Evidence from Eye Movements

The present dissertation examined reading development during elementary school years by means of eye movement tracking. Three different but related issues in this field were assessed. First of all, the development of parafoveal processing skills in reading was investigated. Second, it was assessed whether and to what extent sublexical units such as syllables and morphemes are used in processing Finnish words and whether the use of these sublexical units changes as a function of reading proficiency. Finally, the developmental trend in the speed of visual information extraction during reading was examined. With regard to parafoveal processing skills, it was shown that 2nd graders extract letter identity information approx. 5 characters to the right of fixation, 4th graders approx. 7 characters to the right of fixation, and 6th graders and adults approx. 9 characters to the right of fixation. Furthermore, it was shown that all age groups extract more parafoveal information within compound words than across adjectivenoun pairs of similar length. In compounds, parafoveal word information can be extracted in parallel with foveal word information, if the compound in question is of high frequency. With regard to the use of sublexical units in Finnish word processing, it was shown that less proficient 2nd graders use both syllables and morphemes in the course of lexical access. More proficient 2nd graders as well as older readers seem to process words more holistically. Finally, it was shown that 60 ms is enough for 4th graders and adults to extract visual information from both 4-letter and 8-letter words, whereas 2nd graders clearly needed more than 60 ms to extract all information from 8- letter words for processing to proceed smoothly. The present dissertation demonstrates that Finnish 2nd graders develop their reading skills rapidly and are already at an adult level in some aspects of reading. This is not to say that there are no differences between less proficient (e.g., 2nd graders) and more proficient readers (e.g., adults) but in some respects it seems that the visual system used in extracting information from the text is matured by the 2nd grade. Furthermore, the present dissertation demonstrates that the allocation of attention in reading depends much on textual properties such as word frequency and whether words are spatially unified (as in compounds) or not. This flexibility of the attentional system naturally needs to be captured in word processing models. Finally, individual differences within age groups are quite substantial but it seems that by the end of the 2nd grade practically all Finnish children have reached a reasonable level of reading proficiency.

Cognitive Functions After Traumatic Brain Injury. A 30-year Follow-up Study

Many cognitive deficits after TBI (traumatic brain injury) are well known, such as memory and concentration problems, as well as reduced information-processing speed. What happens to patients and cognitive functioning after immediate recovery is poorly known. Cognitive functioning is flexible and may be influenced by genetic, psychological and environmental factors decades after TBI. The general aim of this thesis was to describe the long-term cognitive course after TBI, to find variables that may contribute to it, and how the cognitive functions after TBI are associated with specific medical factors and reduced survival. The original study group consisted of 192 patients with TBI who were originally assessed with the Mild Deterioration Battery (MDB) on average two years after the injury, during the years 1966 – 1972. During a 30-year follow-up, we studied the risks for reduced survival, and the mortality of the patients was compared with the general population using the Standardized Mortality Ratio (SMR). Sixty-one patients were re-assessed during 1998-2000. These patients were evaluated with the MDB, computerized testing, and with various other neuropsychological methods for attention and executive functions. Apolipoprotein-E (ApoE) genotyping and magnetic resonance imaging (MRI) based on volumetric analysis of the hippocampus and lateral ventricles were performed. Depressive symptoms were evaluated with the short form of the Beck depression inventory. The cognitive performance at follow-up was compared with a control group that was similar to the study group in regard to age and education. The cognitive outcome of the patients with TBI varied after three decades. The majority of the patients showed a decline in their cognitive level, the rest either improved or stayed at the same level. Male gender and higher age at injury were significant risk factors for the decline. Whereas most cognitive domains declined during the follow-up, semantic memory behaved in the opposite way, showing recovery after TBI. In the follow-up assessment, the memory decline and impairments in the set-shifting domain of executive functions were associated with MRI-volumetric measures, whereas reduction in information-processing speed was not associated with the MRI measures. The presence of local contusions was only weakly associated with cognitive functions. Only few cognitive methods for attention were capable of discriminating TBI patients with and without depressive symptoms. On the other hand, most complex attentional tests were sensitive enough to discriminate TBI patients (non-depressive) from controls. This means that complex attention functions, mediated by the frontal lobes, are relatively independent of depressive symptoms post-TBI. The presence of ApoE4 was associated with different kinds of memory processes including verbal and visual episodic memory, semantic memory and verbal working memory, depending on the length of time since TBI. Many other cognitive processes were not affected by the presence of ApoE4. Age at injury and poor vocational outcome were independent risk factors for reduced survival in the multivariate analysis. Late mortality was higher among younger subjects (age < 40 years at death) compared with the general population which should be borne in mind when assessing the need for rehabilitation services and long-term follow-up after TBI.

Correção laparoscópica de hérnia diafragmática traumática crônica

Diaphragmatic hernia secondary to blunt or penetrating trauma is rarely by itself a fatal event. However, if unpercieved, it may lead to severe complications caused by herniation of abdominal contents to the ethorax. Blunt trauma related to car accidents is the most frequent cause of diaphragmatic hernias. Associated injuries are frequently observed, provoked by severe traumas of great impact. These blunt trauma hernias occur mainly on the left side due to abdominal anatomy, since the liver is usually located on the right side. When injuries are observed on the right they tend to be more severe, generally related to major trauma of solid organs. Less frequently diaphragmatic hernias may be bilateral. The management of diaphragmatic injury would appear to be a simple matter of suturing the defect. However, peroperative diagnosis can be difficult and even at the time of surgery some diaphragmatic injuries can be overlooked if carefull exploration is not done. Associated injuries tend to divert attention from the diaphragmatic injury. Laparoscopic diagnosis and repair have been described with successfull. Laparotomy or thoracotomy can be employed for surgical repair of traumatic diaphragmatic hernias. Standard (laboratory/imaging) examinations may fail to make the diagnosis. Recently, the laparoscopic approach has proved useful for more precise evaluation of such injuries, very often allowing immediate repair of these lesions.

Ferimento transfixante de útero em gestante

In de past 50 years, maternal mortality rates have declined, in contrast, the number of deaths due to injury during pregnancy is on the rise. The authors report a case of 24° week pregnant woman victim of penetrating abdominal trauma by gunshot who sustained a grade I11 transfixing injury of the uterine fundus. Treatment was conservative regarding the fetus. Hysteroraphia of the injuries was executed with closure of both penetrating orifices. Obstetrical-gynecological evaluation and echogram documented letal viability in the post-operative period. Post-operative follow-up was performed with periodical echograms up to delivery on the ninth month. Clinical findings, treatment and follow-up will be discussed.

Fatores prognósticos de mortalidade em pacientes com trauma cardíaco que chegam à sala de cirurgia

OBJETIVO: Detectar índices de complicações pós-operatórias e de letalidade, identificando fatores de risco (mecanismo de trauma, sítio da lesão cardíaca, local da intervenção cirúrgica, lesões associadas, necessidade de transfusão e escores anatômicos de trauma) em pacientes com traumatismo cardíaco que apresentavam sinais vitais à admissão na sala de operações. MÉTODO: Realizou-se um estudo descritivo e analítico, de cunho retrospectivo, através dos prontuários de 52 pacientes, submetidos à toracotomia para tratamento de lesões cardíacas penetrantes entre julho/91 e março/97 em um centro de trauma no Nordeste do Brasil. RESULTADOS: O instrumento lesivo mais freqüente foi a arma branca em 28 pacientes (53,85%), seguidos pela arma de fogo em 24 (46,15%). A lesão de ventrículo direito isolada ocorreu em 25 casos (48,08%). As medianas dos escores anatômicos de trauma foram: injury severity score (ISS)=26; penetrating trauma index (PTI)=23; penetrating thoracic trauma index (PTTI)=20; e penetrating cardiac trauma index (PCTI)=15. A taxa de complicação pós-operatória foi de 36,54% e a de letalidade de 13,45%. O sangramento pós-operatório, a necessidade de reoperação e o uso de mais de três concentrados de hemácias aumentaram o risco relativo de morte. Os escores anatômicos de trauma não estiveram associados a aumento do risco relativo de letalidade. CONCLUSÕES: A maioria dos pacientes com lesão cardíaca desta série apresentou bons fatores prognósticos, justificando a baixa taxa de mortalidade observada.

Hérnia diafragmática traumática

Traumatic diaphragmatic hernia is an uncommon but important problem in the patient with multiple injuries. Since diaphragmatic injuries are difficult to diagnose, those that are missed may present with latent symptoms of bowel obstruction and strangulation. The same may occur in the patients with stab wounds to the lower chest. Traumatic diaphragmatic hernia should be suspected on the basis of an abnormal chest radiograph in the trauma victim with multiple injuries. This article discuss about history, epidemiology, clinical signs and symptoms, diagnostic modalities, treatment and complications.

Management of stab wounds to the anterior abdominal wall

The meeting of the Publication "Evidence Based Telemedicine - Trauma and Emergency Surgery" (TBE-CiTE), through literature review, selected three recent articles on the treatment of victims stab wounds to the abdominal wall. The first study looked at the role of computed tomography (CT) in the treatment of patients with stab wounds to the abdominal wall. The second examined the use of laparoscopy over serial physical examinations to evaluate patients in need of laparotomy. The third did a review of surgical exploration of the abdominal wound, use of diagnostic peritoneal lavage and CT for the early identification of significant lesions and the best time for intervention. There was consensus to laparotomy in the presence of hemodynamic instability or signs of peritonitis, or evisceration. The wound should be explored under local anesthesia and if there is no injury to the aponeurosis the patient can be discharged. In the presence of penetration into the abdominal cavity, serial abdominal examinations are safe without CT. Laparoscopy is well indicated when there is doubt about any intracavitary lesion, in centers experienced in this method.

Is there a role for pyloric exclusion after severe duodenal trauma?

Duodenal trauma is an infrequent injury, but linked to high morbidity and mortality. Surgical management of duodenal injuries is dictated by: patient's hemodynamic status, injury severity, time of diagnosis, and presence of concomitant injuries. Even though most cases can be treated with primary repair, some experts advocate adjuvant procedures. Pyloric exclusion (PE) has emerged as an ancillary method to protect suture repair in more complex injuries. However, the effectiveness of this procedure is debatable. The "Evidence Based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club performed a critical appraisal of the literature and selected three relevant publications on the indications for PE in duodenal trauma. The first study retrospectively compared 14 cases of duodenal injuries greater than grade II treated by PE, with 15 cases repaired primarily, all of which penetrating. Results showed that PE did not improve outcome. The second study, also retrospective, compared primary repair (34 cases) with PE (16 cases) in blunt and penetrating grade > II duodenal injuries. The authors concluded that PE was not necessary in all cases. The third was a literature review on the management of challenging duodenal traumas. The author of that study concluded that PE is indicated for anastomotic leak management after gastrojejunostomies. In conclusion, the choice of the surgical procedure to treat duodenal injuries should be individualized. Moreover, there is insufficient high quality scientific evidence to support the abandonment of PE in severe duodenal injuries with extensive tissue loss.