Análise semiquantitativa do parênquima distal de pulmões obtidos em autópsia de vítimas de morte por ação do fogo e por sufocação, foi feita para avaliar as alterações em bronquíolos e tecido alveolar (ductos e alvéolos). A análise discriminante dos parâmetros obtidos permitiu classificação de 74% / A semiquantitative analysis of the distal parenchyma in lung autopsies of victims of death by fire and death by suffocation, was done to evaluate the changes in membranous bronchiolar and alveolar tissue (alveolar ducts and alveoli). The discriminant parameters obtained permitted classification of 74% of cases

O transtorno obsessivo compulsivo (TOC) é um transtorno psiquiátrico, caracterizado pela presença de obsessões e / ou compulsões. Estudos de neuroimagem funcional indicam que o TOC é um distúrbio heterogêneo relacionado ao circuito talâmico cortico-estriatal (CSTC) e as áreas que compõem este circuito incluem o nucleus accumbens (NAC), putâmen (PT), núcleo caudado (CN), córtex orbitofrontal (OFC) e o córtex cingulado anterior (ACC). As principais características do CSTC são a inervação do córtex frontal em direção ao estriado e cada pequeno circuito possui características específicas: afetiva/límbica, cognitivo e associativo dorsal e cognitivo ventral e motor. Neste trabalho comparamos o transcriptoma de casos e controles das três áreas estriatais (CN, NAC e PT) separadamente de tecido cerebral post mortem e as redes de co-expressão do striatum e de dois circuitos envolvidos no transtorno. Os resultados mostraram que diferentes processos biológicos, bem como a desregulação da conectividade de rede, são específicos para cada região do estriado e estão de acordo com o modelo tripartido do estriado e contribuem de diferentes formas para a fisiopatologia do TOC. Especificamente, a regulação dos níveis de neurotransmissores, processo pré-sináptico envolvido na transmissão sináptica química foram compartilhados entre NAC e PT. A resposta celular ao estímulo químico, resposta ao estímulo externo, resposta à substância orgânica, regulação da plasticidade sináptica e modulação da transmissão sináptica foram compartilhadas entre CN e PT. A maioria dos genes que possuem variantes comuns e / ou raras previamente associadas ao TOC que são diferencialmente expressas ou que fazem parte de módulos de co-expressão menos preservados em nosso estudo também sugerem especificidade de cada região estriatal. Os módulos de co-expressão preservados e menos preservados nos circuitos afetivo e cognitivo ventral corroboram com as assinaturas transcricionais de cada área e de cada circuito no TOC e nos controles. Este é o primeiro trabalho com a proposta de avaliar a expressão gênica em áreas estriatais, analisadas individualmente, envolvidas com o TOC, bem como as redes de co-expressão do estriado e dos circuitos individualmente / Obsessive compulsive disorder (OCD) is a psychiatric disorder, characterized by the presence of obsessions and/or compulsions. Functional neuroimaging studies indicate that OCD is a heterogeneous disorder related the cortical-striatal thalamic circuitry (CSTC) and the areas that compose this circuitry include the nucleus accumbens (NAC), putamen (PT), caudate nucleus (CN), orbitofrontal cortex (OFC) and subgenual cingulate gyri (ACC). The main characteristics of CSTC is the innervation of the frontal cortex in direction of the striatum and each small circuitries have specific characteristics in the affective, dorsal cognitive and ventral cognitive motor. In this work we compared the cases and controls transcriptome of the three striatal areas (CN, NAC and PT) separately from post mortem brain tissue and the co-expression networks of the striatum and of two circuits involved in the disorder. Results showed that different biological process as well as networks connectivity deregulation were specific for each striatum region according to the striatum tripartite model and contribute in different ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels, presynaptic process involved in chemical synaptic transmission were shared between NAC and PT. Cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that are differentially expressed or part of a least preserved co-expression modules in our study also suggest striatum sub regions specificity. The co-expression modules preserved and least preserved in affective and ventral cognitive circuitry corroborate with transcriptional signatures of each area and each circuitry in OCD and controls. This is the first work with the proposal to evaluate the gene expression in striatum areas individually, involved with OCD as well evaluate the coexpression networks in striatum and each circuitry

<p>Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. </p><p>Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.</p><p>Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.</p><p>A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.</p><p>Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.</p>

Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease. Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor. A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions. Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

Rationale: Vital registration is lacking in developing settings where health and development problems are most pressing. Policy-makers confront an “information paradox”: the critical need for information on which to base priorities and monitor progress, and the profound shortage of such information. Aims: To better understand the dynamics of mortality transition in rural South Africa over a decade of profound socio-political change coupled with emerging HIV/AIDS. Thereby to inform health and development programming, policy formulation, and the research agenda; and contribute to debate on the nature of the ‘health transition’. Methods: The Agincourt health and demographic surveillance system is based on continuous monitoring of the Agincourt sub-district population in rural north-east South Africa. This involves annual recording of all vital events, specifically deaths, births and migrations in 11,700 households comprising some 70,000 persons. A “verbal autopsy” is conducted on every death, and special modules provide additional data. Key findings: A major health transition has occurred over the past decade, with marked changes in population structure and rapidly escalating mortality particularly among children and younger adults. A quadruple burden of disease is evident with persisting infectious disease and malnutrition in children, emerging non-communicable disease in the middle-aged and older, high levels of violence in an apparently peaceful community, and rapidly escalating HIV/AIDS and tuberculosis. There is evidence of sex differences and socio-economic differentials in mortality; vulnerable sub-groups include the children of Mozambican immigrants and recently returned labour migrants. Implications: With respect to health transition, empirical data demonstrate a marked “counter transition” with mortality increasing in children and young adults; “epidemiologic polarization” is evident with the most vulnerable experiencing a higher mortality burden; and a “protracted transition” is reflected in the co-existence of persisting infectious disease and malnutrition, emerging HIV/AIDS, and increasing chronic non-communicable disease. With respect to health policy and practice there is urgent need to: strengthen HIV/AIDS prevention, treatment and care; offer effective long-term care to control the rising burden of chronic illness and related risk; maintain and improve maternal and child health services; and address differential access to care. This poses a substantial challenge to a severely stretched health system.

Die klinische Obduktion erfüllt heutzutage vor allem Aufgaben in der Qualitätssicherung. Trotz eines hohen individuellen und gesundheitspolitischen Stellenwertes fällt die Zahl der tatsächlich durchgeführten Sektionen seit Jahrzehnten weltweit. Die Gründe für das Absinken sind multifaktoriell. In der vorliegenden Arbeit wird die Rolle des zuletzt behandelnden Arztes untersucht, der bei der Initialisierung des Vorganges (Arztgespräch mit den Angehörigen, Dokumentation, Anmeldung der Obduktion) eine wichtige Rolle spielt. Zu diesem Zweck wurden die von 2005 bis 2012 am Ev. Diakonissenkrankenhaus Leipzig durchgeführten 194 Obduktionen ausgewertet. Durch krankenhausweite, arzt-zentrierte Mittel der Hilfestellung, Schulung und Formalisierung im Jahr 2009 gelang es, die Autopsierate am akademischen Lehrkrankenhaus der Regelversorgung von 3,3% auf 26% zu steigern. Im Rahmen der Untersuchung wurden klinisch vermutete und autoptisch nachgewiesene Todesursachen verglichen und die Ergebnisse in Fehlerklassen eingeteilt. Im Kontrollzeitraum vor dem Maßnahmenpaket wurde eine Gesamt-Fehlerrate von 54% in den Todesursachen (davon 18,8 % prognoserelevante Fehler) festgestellt. Nach Intervention konnte ein Absinken der Gesamt-Fehlerrate auf 27,9% (davon 11,6% prognoserelevante Diskrepanzen) gemessen werden. Nach Gruppierung der autoptisch erhobenen Todesursachen wurden „einfache“ und „schwierige“ Diagnosen erarbeitet. Dabei zeigten sich Lungenembolien (45,5% Fehleinschätzung), Infektionen (13,7% Fehleinschätzung) und akut dekompensierte Herzinsuffizienzen (8,8% Fehleinschätzung) als am häufigsten klinisch verkannte todesursächliche Krankheiten. Eine Sektionsfrequenz von ca. 30% wird als ausreichende epidemiologische Datengrundlage zur Validierung der Todesursachenstatistik angesehen (Bundesärztekammer 2005). In Deutschland beträgt die Rate aktuell etwa 4%. Bemüht man sich um eine Steigerung der Obduktionsrate, ist die Rolle des zuletzt behandelnden Arztes hervorzuheben. In der vorliegenden Arbeit konnte durch einfache Mittel der Beseitigung von Unsicherheiten, Schulung und Formalisierung (SOP) eine deutliche Steigerung der Rate an Sektionen ermöglicht werden. In Konsequenz wurde ein Absinken der Diagnose-Diskrepanzrate und der Anzahl an prognoserelevanten Irrtümern (18,8% auf 11,6%) in den Todesursachen festgestellt. Ob dies allein einen didaktischen Erfolg der vermehrten Behandlungsnachschau darstellt, oder statistische Effekte (verringerter Selektionsbias) beinhaltet, muss offen bleiben. Auffällig ist die Schlüsselstellung der Intensivtherapiestation. Da hier aufgrund der Erkrankungsschwere die höchste Patientensterblichkeit im Krankenhaus vorliegt (25% der pro Jahr Versterbenden), ist eine positive Einstellung der ärztlichen Kollegen gegenüber der Obduktion von entscheidender Bedeutung. Das Maßnahmenpaket ist auf andere Einrichtungen übertragbar und ein für Ärzteschaft und Geschäftsführung lohnender Aufwand, da neben sämtlichen individuellen Vorteilen für Angehörige und Mediziner die Ergebnisse einer solchen Auswertung als globale Qualitätsindikatoren für ein Krankenhaus dienen können.

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Introduction: The burden of road traffic injuries (RTI) is worsening globally, particularly in low- and middle-income countries (LMIC) and among the young and economically productive populations. A major barrier to improving road safety in India and other LMIC is that existing RTI data sources are severely limited by poor population coverage and data quality. This dissertation explores the reliability and feasibility of using a novel data source with verbal autopsy (VA) methods for the purposes of RTI surveillance in India. Methods: The reliability of the VA methods was assessed using physician agreement on the specific categories of injury death as the metric. Next, a nationally representative household mortality survey with VA methods was used to directly estimate the age- and gender-specific RTI death rates and to identify context-specific RTI risk factors in India. Finally, a national spatial database was constructed to quantify potential access to trauma care in relation to the spatial distribution of RTI deaths in India. Results: Across a broad array of application settings in India, the level of physician agreement was high indicating that the VA methods were reliable in distinguishing RTI deaths among other specific categories of injury deaths. The estimated 183,600 RTI deaths in 2005 from the mortality survey were over 50% more than the national police statistics. Of these RTI deaths, 65% were males between ages 15-59 years, 68% were pedestrians and other vulnerable road users, and over 55% occurred at the scene of collision, within minutes of collision, and/or involved a head injury. The existing community health centres and district hospitals in the Indian public health system had inadequate trauma care capacity but were suitably located to allow broad spatial access to timely trauma care for the majority of RTI deaths in India, which were most problematic in the northern states of Punjab, Haryana, Himachal Pradesh and in Tamil Nadu. Conclusions: Properly designed VA studies can provide accurate and reliable RTI surveillance data and assist in identifying context-specific road safety interventions.

How do medical students experience autopsy demonstrations that form part of the undergraduate curriculum? This was the primary question guiding this phenomenological study within the interpretive paradigm. Both explicit cognitive outcomes and elements of the “hidden curriculum” associated with autopsies were evaluated. Most previous studies on this topic employed survey questionnaires and were conducted prior to the radical curriculum reformations in medical undergraduate training. Some of these pedagogical changes have threatened the use of autopsies for teaching. More recently some other studies concentrated on aspects that were not directly related to educational outcomes. Burton (2003) conducted a phenomenological study interviewing medical educators about the uses of autopsy in the modern undergraduate curriculum, essentially detailing the “delivered curriculum”. Therefore this study focused on the “received curriculum”. Interviews were conducted with 10 medical students in their 4th year of study, having attended medico-legal autopsy demonstrations forming a central part of a course in Forensic Medicine. The underlying assumption of the study is that ‘student voices’ need to be heard in determining what is taught and how (Brooker & MacDonald, 1999), something typically determined by academic staff. This need is especially highlighted in a climate of “self-directed learning” promoted by modern medical curricula. The data are analysed qualitatively using a theoretical framework of three dimensions of learning (Illeris, 2004): (1) cognitive content dimension, (2) emotional psychodynamic, attitudinal and motivational dimension, (3) social-societal dimension. Findings of the study show that medical students perceive autopsy demonstrations to be of considerable benefit to their learning; both cognitive and affective outcomes are discussed detailing individual contextual factors that influenced the outcomes. Some suggestions regarding curriculum and autopsy-based teaching are made in the light of various factors found to influence students’ attitudes towards autopsies. / Thesis (M.Ed.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.

Introduction: The burden of road traffic injuries (RTI) is worsening globally, particularly in low- and middle-income countries (LMIC) and among the young and economically productive populations. A major barrier to improving road safety in India and other LMIC is that existing RTI data sources are severely limited by poor population coverage and data quality. This dissertation explores the reliability and feasibility of using a novel data source with verbal autopsy (VA) methods for the purposes of RTI surveillance in India. Methods: The reliability of the VA methods was assessed using physician agreement on the specific categories of injury death as the metric. Next, a nationally representative household mortality survey with VA methods was used to directly estimate the age- and gender-specific RTI death rates and to identify context-specific RTI risk factors in India. Finally, a national spatial database was constructed to quantify potential access to trauma care in relation to the spatial distribution of RTI deaths in India. Results: Across a broad array of application settings in India, the level of physician agreement was high indicating that the VA methods were reliable in distinguishing RTI deaths among other specific categories of injury deaths. The estimated 183,600 RTI deaths in 2005 from the mortality survey were over 50% more than the national police statistics. Of these RTI deaths, 65% were males between ages 15-59 years, 68% were pedestrians and other vulnerable road users, and over 55% occurred at the scene of collision, within minutes of collision, and/or involved a head injury. The existing community health centres and district hospitals in the Indian public health system had inadequate trauma care capacity but were suitably located to allow broad spatial access to timely trauma care for the majority of RTI deaths in India, which were most problematic in the northern states of Punjab, Haryana, Himachal Pradesh and in Tamil Nadu. Conclusions: Properly designed VA studies can provide accurate and reliable RTI surveillance data and assist in identifying context-specific road safety interventions.