O cuidado psicológico ao médico em reprodução assistida: um enquadre diferenciado

Profissionais da área da saúde entram em contato com o sofrimento humano mesmo quando não trabalham diretamente no campo da Psicologia. Este estudo baseou-se no referencial da psicanálise com vistas a compreender os aspectos do sofrimento humano que emerge para os médicos no exercício da reprodução assistida, e a importância do estudo do imaginário coletivo sobre situações de difícil manejo em suas clínicas. Participaram vinte e dois médicos que atuam em hospitais e clínicas do estado de São Paulo em âmbitos público e privado, independentemente de sexo, idade e tempo de formação. Foi utilizado o procedimento desenhos-estórias com tema, compreendido como procedimento dialógico. A entrevista caracterizou-se como uma situação especial de comunicação e expressão das emoções geradas nos atendimentos relacionados à temática proposta. Constatou-se a necessidade de proposição de espaços facilitadores da expressão emocional, que promovem a continência do sofrimento humano e a ocorrência de experiências reflexivo-vivenciais transformadoras do real.

Well-being, distress and health status in a population of adolescent students

The present work explores the psychosocial issues emerging from a large cross-sectional study aimed to assess the prevalence, clinical manifestations, and psychosocial correlates of hyperandrogenism in a population of Italian high school students. Participants were 1804 adolescents, aged between 15 and 19 years, who volunteered to fill in a package of self-report questionnaires (including the Psychosocial Index, the Symptom Questionnaire and Ryff’s Psychological Well-Being scales for the assessment of psychological aspects) and undergo a comprehensive physical examination. Significant gender differences were found with regard to psychological distress, with females reporting higher scores compared with males, but not on well-being dimensions. The relationships of well-being to distress were found to be complex. Although inversely associated, well-being and ill-being appeared to be distinct domains of mental functioning. The evaluation of the moderating effects of well-being in the association between stress and psychological distress indicated that well-being may act as a protective factor, contributing to less pronounced psychological distress as stress levels increased. Higher rates of somatic complaints were found among current smokers. However, substance use (i.e., smoking and drug use) was also found to be positively associated with some well-being dimensions. A considerable number of participants were found to present with disordered eating symptoms, particularly females, and associated higher stress levels and lower quality of life. Sport activities were found to favourably affect psychological health. As to clinical signs of hyperandrogenism, a significant impairment in psychosocial functioning was found among females, whereas no effects on psychological measures could be detected among males. Subgroups of adolescents with distinct clinical and psychological characteristics could be identified by means of cluster analysis. The present study provides new insights into better understanding of the complex relationships between well-being, distress and health status in the adolescent population, with important clinical implications.

Le Coliti Microscopiche nei soggetti con diarrea non ematica: uno studio prospettico

Introduzione: le Coliti Microscopiche, altrimenti note come Colite Collagena e Colite Linfocitica, sono disordini infiammatori cronici del colon che causano diarrea e colpiscono più frequentemente donne in età avanzata e soggetti in terapia farmacologica. Negli ultimi anni la loro incidenza sembra aumentata in diversi paesi occidentali ma la prevalenza in Italia è ancora incerta. Scopo: il presente studio prospettico e multicentrico è stato disegnato per valutare la prevalenza delle CM in pazienti sottoposti a colonscopia per diarrea cronica non ematica. Pazienti e metodi: dal Maggio 2010 al Settembre 2010 sono stati arruolati consecutivamente tutti i soggetti adulti afferenti in due strutture dell’area metropolitana milanese per eseguire una pancolonscopia. Nei soggetti con diarrea cronica non ematica sono state eseguite biopsie multiple nel colon ascendente, sigma e retto nonché in presenza di lesioni macroscopiche. Risultati: delle 8008 colonscopie esaminate 265 sono state eseguite per diarrea cronica; tra queste, 8 presentavano informazioni incomplete, 52 riscontri endoscopici consistenti con altri disordini intestinali (i.e. IBD, tumori, diverticoliti). 205 colonscopie sono risultate sostanzialmente negative, 175 dotate di adeguato campionamento microscopico (M:F=70:105; età mediana 61 anni). L’analisi istologica ha permesso di documentare 38 nuovi casi di CM (M:F=14:24; età mediana 67.5 anni): 27 CC (M:F=10:17; età mediana 69 anni) e 11 CL (M:F=4:7; età mediana 66 anni). In altri 25 casi sono state osservate alterazioni microscopiche prive dei sufficienti requisiti per la diagnosi di CM. Conclusioni: nel presente studio l’analisi microscopica del colon ha identificato la presenza di CM nel 21,7% dei soggetti con diarrea cronica non ematica ed indagine pancolonscopica negativa. Lo studio microscopico del colon è pertanto un passo diagnostico fondamentale per il corretto inquadramento diagnostico delle diarree croniche, specialmente dopo i 60 anni di età. Ampi studi prospettici e multicentrici dovranno chiarire ruolo e peso dei fattori di rischio associati a questi disordini.

[Chronic right-sided pain-associated nondermatomal somatosensory deficit following an accident]

We present the case of a 48-year old man who, eight years after an industrial accident, presents with chronic right-sided nondermatomal pain and hypaesthesia to heat and touch. During symmetric peripheral touch functional magnetic resonance imaging revealed hypometabolism in the left thalamus, somatosensory cortex, and anterior cingulate cortex. Pain-associated nondermatomal somatosensory deficits (NDSDs) localizing to one side of the body are a frequent clinical entity, which are often triggered by an accident. The tendency of NDSDs to extend to adjunct ipsilateral body parts and to become chronic points to maladaptive adjustment of pain-processing areas in the central nervous system. Psychological stress prior to or around the triggering event seems an important risk factor for NDSDs.

Acquired factor XIII deficiency: a therapeutic challenge

Less than 60 cases of acquired factor (F)XIII deficiencies have been reported, most having distinct clinical features. To illustrate the therapeutic challenges of acquired FXIII inhibitors, we report a case of a 65-year-old patient with no previous bleeding history who suddenly developed massive haemorrhages associated to a strong and isolated FXIII inhibitor. No underlying disorder has been detected till now after three years of follow-up. Despite aggressive treatment with prednisone, rituximab, cyclophosphamide, immunoglobulin, immunoadsorption and immune tolerance his inhibitor is still present, although at low titre and with a clinical benefit since the patient has no more bleed since more than one year. Moreover the patient had a venous thromboembolic complication. After a review of the management of acquired FXIII deficiency patients and based on the management of acquired haemophilia we discuss a possible strategy for such difficult cases.

Health related quality of life: a changing construct?

In 186 patients with early colon cancer, we investigated the assumption that the meaning of 'quality of life' (QL) remains constant over time. Within a phase-III trial (SAKK 40/93), patients estimated both their overall QL and a range of disease- and treatment-related domains at five timepoints, comprising three concurrent and 2 retrospective estimates: their pre-surgery QL both before surgery and retrospectively thereafter, and their pre-adjuvant QL both at the beginning of adjuvant treatment and retrospectively about 2 months later, and their current QL 2 weeks thereafter. Multilevel models were developed to determine whether the selected domains made stable contributions to overall QL at the concurrent estimates. The weights of the domains changed over time. They did not differ significantly according to whether patients were considering their concurrent state or reflecting on this state at a later timepoint. In the process of adaptation, patients with early colon cancer substantially change the relative importance of QL domains to overall QL. This finding argues for QL as a changing construct and against the assumption that domain-specific weights are stable across distinct clinical phases.

C1 esterase inhibitor reduces lower extremity ischemia/reperfusion injury and associated lung damage

BACKGROUND Ischemia/reperfusion injury of lower extremities and associated lung damage may result from thrombotic occlusion, embolism, trauma, or surgical intervention with prolonged ischemia and subsequent restoration of blood flow. This clinical entity is characterized by high morbidity and mortality. Deprivation of blood supply leads to molecular and structural changes in the affected tissue. Upon reperfusion inflammatory cascades are activated causing tissue injury. We therefore tested preoperative treatment for prevention of reperfusion injury by using C1 esterase inhibitor (C1 INH). METHODS AND FINDINGS Wistar rats systemically pretreated with C1 INH (n = 6), APT070 (a membrane-targeted myristoylated peptidyl construct derived from human complement receptor 1, n = 4), vehicle (n = 7), or NaCl (n = 8) were subjected to 3h hind limb ischemia and 24h reperfusion. The femoral artery was clamped and a tourniquet placed under maintenance of a venous return. C1 INH treated rats showed significantly less edema in muscle (P<0.001) and lung and improved muscle viability (P<0.001) compared to controls and APT070. C1 INH prevented up-regulation of bradykinin receptor b1 (P<0.05) and VE-cadherin (P<0.01), reduced apoptosis (P<0.001) and fibrin deposition (P<0.01) and decreased plasma levels of pro-inflammatory cytokines, whereas deposition of complement components was not significantly reduced in the reperfused muscle. CONCLUSIONS C1 INH reduced edema formation locally in reperfused muscle as well as in lung, and improved muscle viability. C1 INH did not primarily act via inhibition of the complement system, but via the kinin and coagulation cascade. APT070 did not show beneficial effects in this model, despite potent inhibition of complement activation. Taken together, C1 INH might be a promising therapy to reduce peripheral ischemia/reperfusion injury and distant lung damage in complex and prolonged surgical interventions requiring tourniquet application.

Temporohyoid osteoarthropathy in the horse

Temporohyoid osteoarthropathy (THO) is a well-recognised clinical entity in horses. Temporohyoid osteoarthropathy is characterised by progressive osseous proliferation of the proximal portion of the stylohyoid and petrous temporal bones, and is generally described as a disease of middle-aged horses. More recent reports also attribute a variety of clinical syndromes in young horses to THO, requiring a diversification of approaches to confirm the diagnosis and its significance, and to guide conservative and surgical treatment options. This commentary will review the purported aetiology, clinical syndromes, available diagnostic tests and treatment options of equine THO.

Paradoxical embolism.

Paradoxical embolism is an important clinical entity among patients with venous thromboembolism in the presence of intracardiac or pulmonary shunts. The clinical presentation is diverse and potentially life-threatening. Although the serious nature and complications of paradoxical embolism are recognized, the disease entity is still rarely considered and remains under-reported. This paper provides an overview on the different clinical manifestations of paradoxical embolism, describes the diagnostic tools for the detection of intracardiac and pulmonary shunts, reviews therapeutic options, and summarizes guideline recommendations for the secondary prevention of paradoxical embolism.

EMAS position statement: Testosterone replacement therapy in the aging male‏.

INTRODUCTION Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. AIMS The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.

The Effect of Incidental Consolidation on Management and Outcomes in COPD Exacerbations: Data from the European COPD Audit

OBJECTIVE There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. PATIENTS AND METHODS The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. RESULTS 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. CONCLUSIONS Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.

William Osler: Original Papers 1898-1906

Part 1: 1898-1899 On Chronic Symmetrical Enlargement of the Salivary and Lachrymal Glands, 1898 Leprosy in the United States, with the Report of a Case, 1898 An Acute Myxaedematous Condition, with Tachycardia, Glycosuria, Melaena, Mania and Death, 1898 On some of the Intestinal Features of Typhoid Fever, 1898 Cerebro-Spinal Fever, 1898 The Arthritis of Cerebro-Spinal Fever, 1898 In Memoriam, William Pepper, 1899 After Twenty-Five Years, 1899 The Diagnosis of Typhoid Fever, 1899 Interstitial Processes in the Central Nervous System, 1899 Part 2: 1900 The Home Treatment of Consumption, 1900 On Splenic Anaemia, 1900 The Chronic Intermittent Fever of Endocarditis, 1900 A Case of Multiple Gangrene in Malarial Fever, 1900 Latent Cancer of the Stomach, 1900 On the Study of Tuberculosis, 1900 Fatal Angina Pectoris without Lesions of the Coronary Arteries of a Young Man, 1900 On the Advantages of a Trace of Albumin and a Few Casts in the Urine of Certain Men above Fifty Years of Age, 1900 Part 3: 1901-1902 Congenital Absence of the Abdominal Muscles with Distended Hypertrophied Urinary Bladder, 1901 Intermittent Claudication, 1902 On the Diagnosis of Bilateral Cystic Kidney, 1902 On Amebic Abscess of the Liver, 1902 Note on the Occurrence of Ascites in Solid Abdominal Tumors, 1902 Amebic Dysentery, 1902 Notes on Aneurism, 1902 William Beaumont; a Pioneer American Physiologist, 1902 Part 4: 1903 On the Educational Value of the Medical Society, 1903 On obliteration of the Superior Vena Cava,1903 Chronic Cyanosis, with Polycythemia and Enlarged Spleen: A New Clinical Entity, 1903 The Home and its Relation to the Tuberculosis Problem, 1903 Unity, Peace, and Concord, 1903 Typhoid Fever and Tuberculosis, 1903 Part 5: 1904-1906 Ochronosis, 1904 The “Phthisiologia” of Richard Morton, M.D., 1904 On the Surgical Importance of the Visceral Crises In the Erythema Group of Skin Diseases, 1904 Aneurysm of the Abdominal Aorta, 1905 Back Notes

Multimodal integration of functional and structural brain connectivity. An application to the characterization of Mild Cognitive Impairment

La investigación para el conocimiento del cerebro es una ciencia joven, su inicio se remonta a Santiago Ramón y Cajal en 1888. Desde esta fecha a nuestro tiempo la neurociencia ha avanzado mucho en el desarrollo de técnicas que permiten su estudio. Desde la neurociencia cognitiva hoy se explican muchos modelos que nos permiten acercar a nuestro entendimiento a capacidades cognitivas complejas. Aun así hablamos de una ciencia casi en pañales que tiene un lago recorrido por delante. Una de las claves del éxito en los estudios de la función cerebral ha sido convertirse en una disciplina que combina conocimientos de diversas áreas: de la física, de las matemáticas, de la estadística y de la psicología. Esta es la razón por la que a lo largo de este trabajo se entremezclan conceptos de diferentes campos con el objetivo de avanzar en el conocimiento de un tema tan complejo como el que nos ocupa: el entendimiento de la mente humana. Concretamente, esta tesis ha estado dirigida a la integración multimodal de la magnetoencefalografía (MEG) y la resonancia magnética ponderada en difusión (dMRI). Estas técnicas son sensibles, respectivamente, a los campos magnéticos emitidos por las corrientes neuronales, y a la microestructura de la materia blanca cerebral. A lo largo de este trabajo hemos visto que la combinación de estas técnicas permiten descubrir sinergias estructurofuncionales en el procesamiento de la información en el cerebro sano y en el curso de patologías neurológicas. Más específicamente en este trabajo se ha estudiado la relación entre la conectividad funcional y estructural y en cómo fusionarlas. Para ello, se ha cuantificado la conectividad funcional mediante el estudio de la sincronización de fase o la correlación de amplitudes entre series temporales, de esta forma se ha conseguido un índice que mide la similitud entre grupos neuronales o regiones cerebrales. Adicionalmente, la cuantificación de la conectividad estructural a partir de imágenes de resonancia magnética ponderadas en difusión, ha permitido hallar índices de la integridad de materia blanca o de la fuerza de las conexiones estructurales entre regiones. Estas medidas fueron combinadas en los capítulos 3, 4 y 5 de este trabajo siguiendo tres aproximaciones que iban desde el nivel más bajo al más alto de integración. Finalmente se utilizó la información fusionada de MEG y dMRI para la caracterización de grupos de sujetos con deterioro cognitivo leve, la detección de esta patología resulta relevante en la identificación precoz de la enfermedad de Alzheimer. Esta tesis está dividida en seis capítulos. En el capítulos 1 se establece un contexto para la introducción de la connectómica dentro de los campos de la neuroimagen y la neurociencia. Posteriormente en este capítulo se describen los objetivos de la tesis, y los objetivos específicos de cada una de las publicaciones científicas que resultaron de este trabajo. En el capítulo 2 se describen los métodos para cada técnica que fue empleada: conectividad estructural, conectividad funcional en resting state, redes cerebrales complejas y teoría de grafos y finalmente se describe la condición de deterioro cognitivo leve y el estado actual en la búsqueda de nuevos biomarcadores diagnósticos. En los capítulos 3, 4 y 5 se han incluido los artículos científicos que fueron producidos a lo largo de esta tesis. Estos han sido incluidos en el formato de la revista en que fueron publicados, estando divididos en introducción, materiales y métodos, resultados y discusión. Todos los métodos que fueron empleados en los artículos están descritos en el capítulo 2 de la tesis. Finalmente, en el capítulo 6 se concluyen los resultados generales de la tesis y se discuten de forma específica los resultados de cada artículo. ABSTRACT In this thesis I apply concepts from mathematics, physics and statistics to the neurosciences. This field benefits from the collaborative work of multidisciplinary teams where physicians, psychologists, engineers and other specialists fight for a common well: the understanding of the brain. Research on this field is still in its early years, being its birth attributed to the neuronal theory of Santiago Ramo´n y Cajal in 1888. In more than one hundred years only a very little percentage of the brain functioning has been discovered, and still much more needs to be explored. Isolated techniques aim at unraveling the system that supports our cognition, nevertheless in order to provide solid evidence in such a field multimodal techniques have arisen, with them we will be able to improve current knowledge about human cognition. Here we focus on the multimodal integration of magnetoencephalography (MEG) and diffusion weighted magnetic resonance imaging. These techniques are sensitive to the magnetic fields emitted by the neuronal currents and to the white matter microstructure, respectively. The combination of such techniques could bring up evidences about structural-functional synergies in the brain information processing and which part of this synergy fails in specific neurological pathologies. In particular, we are interested in the relationship between functional and structural connectivity, and how two integrate this information. We quantify the functional connectivity by studying the phase synchronization or the amplitude correlation between time series obtained by MEG, and so we get an index indicating similarity between neuronal entities, i.e. brain regions. In addition we quantify structural connectivity by performing diffusion tensor estimation from the diffusion weighted images, thus obtaining an indicator of the integrity of the white matter or, if preferred, the strength of the structural connections between regions. These quantifications are then combined following three different approaches, from the lowest to the highest level of integration, in chapters 3, 4 and 5. We finally apply the fused information to the characterization or prediction of mild cognitive impairment, a clinical entity which is considered as an early step in the continuum pathological process of dementia. The dissertation is divided in six chapters. In chapter 1 I introduce connectomics within the fields of neuroimaging and neuroscience. Later in this chapter we describe the objectives of this thesis, and the specific objectives of each of the scientific publications that were produced as result of this work. In chapter 2 I describe the methods for each of the techniques that were employed, namely structural connectivity, resting state functional connectivity, complex brain networks and graph theory, and finally, I describe the clinical condition of mild cognitive impairment and the current state of the art in the search for early biomarkers. In chapters 3, 4 and 5 I have included the scientific publications that were generated along this work. They have been included in in their original format and they contain introduction, materials and methods, results and discussion. All methods that were employed in these papers have been described in chapter 2. Finally, in chapter 6 I summarize all the results from this thesis, both locally for each of the scientific publications and globally for the whole work.

Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene

The xeroderma pigmentosum group D (XPD) protein has a dual function, both in nucleotide excision repair of DNA damage and in basal transcription. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the clinical phenotypes of XP and TTD can be attributed to the sites of the mutations, we have identified the mutations in a large group of TTD and XP-D patients. Most sites of mutations differed between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding patients were all compound heterozygotes with different mutations in the two alleles, the alleles were tested separately in a yeast complementation assay. The mutations which are found in both XP and TTD patients behaved as null alleles, suggesting that the disease phenotype was determined by the other allele. If we eliminate the null mutations, the remaining mutagenic pattern is consistent with the site of the mutation determining the phenotype.

Miocardiopatia arritmogénica do ventrículo direito : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014