Renal involvement in prolonged salmonella bacteremia: the role of schistosomal glomerulopathy

Renal involvement has been well documented in patients with hepatosplenic schistosomiasis and in patients with prolonged salmonella bacteremia (PSB). Whether there is a specific renal lesion related to PSB or the chronic bacterial infection aggravates a pre-existing schistosomal glomerulopathy has been a matter of controversy. To analyze the clinical manifestations and histopathological findings of the renal involvement, 8 patients with hepatosplenic schistosomiasis and PSB (group I) were compared with 8 patients with schistosomal glomerulopathy (group II) matched by sex and glomerular disease. The mean age in group I was 17.7 years. All patients presented with hematuria, in 4 cases associated with non-nephrotic proteinuria. In group II the mean age was 23 years; nephrotic syndrome was the clinical presentation in 7 of the 8 patients in the group. All patients in group I experienced remission of the clinical and laboratory abnormalities as the salmonella infection was cured; in group II the patients had persistent, steroid-resistant, nephrotic syndrome. On histological examination, no difference was noted between the two groups, except for pronounced glomerular hypercellularity and interstitial mononuclear cell infiltration in group I. These observations strongly suggest that PSB exacerbates a pre-existing sub-clinical schistosomal glomerulopathy by the addition of active lesions directly related to the prolonged bacteremia

Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients

Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.

Validação da antropometria e ultrassonografia do braço, para medição dos respectivos compartimentos, em lactentes nascidos pré-termo : contributo para a avaliação corporal do recem-nascido e do lactente

RESUMO: Contexto: Indicadores fidedignos da composição corporal são importantes na orientação das estratégias nutricionais de recém-nascidos e pequenos lactentes submetidos a cuidados intensivos. O braço é uma região acessível para avaliar a composição corporal regional, pela medida dos seus compartimentos. A antropometria e a ultrassonografia (US) são métodos não invasivos, relativamente económicos, que podem ser usados à cabeceira do paciente na medição desses compartimentos, embora esses métodos não tenham ainda sido validados neste subgrupo etário. A ressonância magnética (RM) pode ser usada como método de referência na validação da medição dos compartimentos do braço. Objectivo: Validar em lactentes pré-termo, as medidas do braço por antropometria e por US. Métodos: Foi estudada uma coorte de recém-nascidos admitidos consecutivamente na unidade de cuidados intensivos neonatais, com  33 semanas de idade de gestação e peso adequado para a mesma, sem anomalias congénitas major e não submetidas a diuréticos ou oxigenoterapia no momento da avaliação. Nas vésperas da alta, foram efectuadas medições do braço, com ocultação, pelos métodos antropométrico, ultrassonográfico e RM. As medidas antropométricas directas foram: peso (P), comprimento (C), perímetro cefálico (PC), perímetro braquial (PB) e prega cutânea tricipital (PT). As área braquial total, área muscular (AM) e área adiposa foram calculadas pelos métodos de Jeliffee & Jeliffee e de Rolland-Cachera. Utilizando uma sonda PSH-7DLT de 7 Hz no ecógrafo Toshiba SSH 140A foram medidos os perímetros braquial e muscular e calculadas automaticamente as áreas braquial e muscular, sendo a área adiposa obtida por subtracção. Como método de referência foi utilizada a RM – Philips Gyroscan ACS-NT, Power-Track 1000 ®, 1.5 Tesla com uma antena de quadratura do joelho. Na análise estatística foram utilizados os métodos paramétricos e não paramétricos, conforme adequado. Resultados: Foram incluídas 30 crianças, nascidas com ( ±DP) 30.7 ±1.9 semanas de gestação, pesando 1380 ±325g, as quais foram avaliadas às 35.4 ±1.1 semanas de idade corrigida, quando pesavam 1786 ±93g. Nenhuma das medidas antropométricas, individualmente, constitui um indicador aceitável (r2 <0.5) das medições por RM. A melhor e mais simples equação alternativa encontrada é a que estima a AM (r2 = 0.56), derivada dos resultados da análise de regressão múltipla: AMRM = (P x 0.17) + (PB x 5.2) – (C x 6) – 150, sendo o P expresso em g, o C e o PB em cm. Nenhuma das medidas ultrassonográficas constitui um indicador aceitável (r2 <0.4) das medições por RM. Conclusões: A antropometria e as medidas ultrassonográficas do braço não são indicadores fidedignos da composição corporal regional em lactentes pré-termo, adequados para a idade de gestação.----------ABSTRACT: Background: Accurate predictors for body composition are valuable tools guiding nutritional strategies in infants needing intensive care. The upper-arm is a part of the body that is easily accessible and convenient for assessing the regional body composition, throughout the assessment of their compartments. Anthropometry and by ultrasonography (US) are noninvasive and relatively nonexpensive methods for bedside assessment of the upper-arm compartments. However, these methods have not yet been validated in infants. Magnetic resonance imaging (MRI) may be used as gold standard to validate the measurements of the upper-arm compartments. Objective: To validate the upper-arm measurements by anthropometry and by US in preterm infants. Methods: A cohort of neonates consecutively admitted at the neonatal intensive care unit, appropriate for gestational age, with  33 weeks, without major congenital abnormalities and not subjected to diuretics or oxygen therapy, was assessed. Before the discharge, the upper-arm was blindly measured by anthropometry, US and MRI. The direct anthropometric parameters measured were: weight (W), length (L), head circumference (HC), mid-arm circumference (MAC), and tricipital skinfold thickness. The arm area (AA), arm muscle area (AMA) and arm fat area were calculated applying the methods proposed by Jeliffee & Jeliffee and by Rolland-Cachera. Using the sonolayer Toshiba SSH 140A and the probe PSH-7DLT 7Hz, the arm and muscle perimeters were measured by US, the arm and muscle areas included were automatically calculated, and the fat area was calculated by subtraction. The MR images were acquired on a 1.5-T Philips Gyroscan ACS-NT, Power-Track 1000 scanner, and a knee coil was chosen for the upper-arm measurements. For statistical analysis parametric and nonparametric methods were used as appropriate. Results: Thirty infants born with ( ±SD) 30.7 ±1.9 weeks of gestational age and weighing 1380 ±325g were included in the study; they were assessed at 35.4 ±1.1 weeks of corrected age, weighing 1786 ±93g. None of the anthropometric measurements are individually acceptable (r2 <0.5) for prediction of the measurements obtained by MRI. The best and simple alternative equation found is the equation for prediction of the AMA (r2 = 0.56), derived from the results of multiple regression analysis: AMARM = (W x 0.17) + (MAC x 5.2) – (L x 6) – 150, being the W expressed in g, and L and MAC in cm. None of the ultrasonographic measurements are acceptable (r2 <0.5) predictors for the measurements obtained by MRI. Conclusions: The measurements of the upper-arm by anthropometry and by US are not accurate predictors for the regional body composition in preterm appropriate for gestational age infants.

Peptic disease and Helicobacter pylori are highly prevalent in patients with the indeterminate form of chagas’ disease: report of 21 cases

Given that chagasic patients in the indeterminate form of this disease, can have abnormal motility of the digestive tract and immunologic abnormalities, we decided to assess the frequency of peptic disease and Helicobacter pylori (Hp) infection in these individuals. Twenty-one individuals, 13 males and 8 females, mean age 37.6 ± 11.1 years, were examined. Biopsies of the duodenum, antrum, lesser and greater gastric curvature and esophagus were performed. The endoscopic findings were of chronic gastritis in 20 (95.2%) patients, duodenal ulcer in 3 (14.3%), gastric and duodenal ulcer in 3 (14.3%), gastric ulcer alone in 1 (4.8%), esophagitis in 5 (23.8%), and duodenitis in 5 (23.8%). The diagnosis of infection by the Hp was done by the urease test and histologic examination. Hp infection was found in 20 (95.2%) individuals: in 20 out of them in the antrum, in 17 in the lesser curvature, and in 17 in the greater curvature. Hp was not found in the esophagus and duodenum. The only individual with no evidence of infection by Hp was also the only one with normal endoscopic and histologic examinations. The histologic examinations confirmed the diagnoses of gastric ulcer as peptic, chronic gastritis in 20 patients, duodenitis in 14, and esophagitis in 9. In this series the patients had a high frequency of peptic disease, which was closely associated with Hp infection

Cerebrospinal fluid profiles in acquired immunodeficiency syndrome with and without neurocryptococcosis

Cryptococcosis is one of the most common fungal infections of the central nervous system (CNS) in AIDS patients and meningoencephalitis or meningitis is a frequently observed manifestation. However, systematic studies of cerebrospinal fluid (CSF) composition from AIDS patients with CNS cryptococcosis have been few. CSF samples from 114 HIV seropositive patients whose clinical complaint suggested CNS involvement, were analyzed; 32 samples from patients diagnosed as having neurocryptococcosis (Group 1) and 82 samples from patients with no identified neurological disfunction (Group 2). Based on cytological and biochemical results, two distinct profiles were observed: Normal (Group 1 = 31%, Group 2 = 39%); Abnormal (Group 1 = 69%, Group 2 = 61%). Lymphocytes were the most frequent cells in both groups. Our CSF cytological and biochemical findings showed that in AIDS patients liquoric abnormalities are quite frequent, non-specific and difficult to interpret. In these circumstances a systematic search to identify the etiologic agent using microbiological and/or immunological assays must be routinely performed

Toxicity screening of Diclofenac, Propranolol, Sertraline and Simvastatin using Danio rerio and Paracentrotus lividus embryo bioassays

Early life-stage bioassays have been used as an alternative to short-term adult toxicity tests since they are cost-effective. A single couple can produce hundreds or thousands of embryos and hence can be used as a simple high-throughput approach in toxicity studies. In the present study, zebrafish and sea urchin embryo bioassays were used to test the toxicity of four pharmaceuticals belonging to different therapeutic classes: diclofenac, propranolol, simvastatin and sertraline. Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin embryos, inducing development abnormalities at the ng/L range. Overall, our results highlight the potential of sea urchin embryo bioassay as a promising and sensitive approach for the high-throughput methods to test the toxicity of new chemicals, including pharmaceuticals, and identify several drugs that should go through more detailed toxicity assays.

Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production

ABSTRACT – Background: According to the Report on Carcinogens, formaldehyde ranks 25th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Presently, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans (Group 1), based on sufficient evidence in humans and in experimental animals. Manyfold in vitro studies clearly indicated that formaldehyde can induce genotoxic effects in proliferating cultured mammalian cells. Furthermore, some in vivo studies have found changes in epithelial cells and in peripheral blood lymphocytes related to formaldehyde exposure. Methods: A study was carried out in Portugal, using 80 workers occupationally exposed to formaldehyde vapours: 30 workers from formaldehyde and formaldehyde-based resins production factory and 50 from 10 pathology and anatomy laboratories. A control group of 85 non-exposed subjects was considered. Exposure assessment was performed by applying simultaneously two techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection equipment with simultaneously video recording. Evaluation of genotoxic effects was performed by application of micronucleus test in exfoliated epithelial cells from buccal mucosa and peripheral blood lymphocytes. Results: Time-weighted average concentrations not exceeded the reference value (0.75 ppm) in the two occupational settings studied. Ceiling concentrations, on the other hand, were higher than reference value (0.3 ppm) in both. The frequency of micronucleus in peripheral blood lymphocytes and in epithelial cells was significantly higher in both exposed groups than in the control group (p < 0.001). Moreover, the frequency of micronucleus in peripheral blood lymphocytes was significantly higher in the laboratories group than in the factory workers (p < 0.05). A moderate positive correlation was found between duration of occupational exposure to formaldehyde (years of exposure) and micronucleus frequency in peripheral blood lymphocytes (r = 0.401; p < 0.001) and in epithelial cells (r = 0.209; p < 0.01). Conclusions: The population studied is exposed to high peak concentrations of formaldehyde with a long-term exposure. These two aspects, cumulatively, can be the cause of the observed genotoxic endpoint effects. The association of these cytogenetic effects with formaldehyde exposure gives important information to risk assessment process and may also be used to assess health risks for exposed worker

NEPHROTOXICITY ATTRIBUTED TO MEGLUMINE ANTIMONIATE (GLUCANTIME) IN THE TREATMENT OF GENERALIZED CUTANEOUS LEISHMANIASIS

Background: Pentavalent antimonials have became of basic importance for the treatment of leishmaniasis. Their most severe side effects have been reported to be increased hepatic enzyme levels and electrocardiographic abnormalities. Nephrotoxicity has been rarely related. Observations: We report a case of generalized cutaneous leishmaniasis involving a 50-year old male patient who was submitted to treatment with meglumine antimoniate (Glucantime). He developed acute renal failure (ARF) due to acute tubular necrosis (ATN), followed by death after receiving a total of 53 ampoules of Glucantime. Conclusions: The treatment with Glucantime was responsible by ARF diagnosed in this patient. The previous urine osmolarity and serum creatinine levels were normal and the autopsy showed ATN. It should be pointed out if ARF may also be explained by massive deposits of immunocomplexes by leishmania antibodies and antigens due to the antigenic break by the antimonial compound, since our patient presented countless lesions covering the entire tegument, similar to the Hexheimer phenomenon, but at the autopsy no glomerular alterations were seen.

Sistema de deteção de arritmias

Esta dissertação apresenta o trabalho realizado no âmbito da unidade curricular de Tese/Dissertação (TEDI), do 2º ano, do Mestrado em Engenharia Eletrotécnica e de Computadores no ramo de Automação e Sistemas. O principal objetivo desta dissertação consiste no desenvolvimento de um sistema que permita efetuar a deteção de um determinado número de anomalias num sinal eletrocardiográfico. O coração é um dos órgãos mais importantes do corpo humano. É ele que recebe e bombeia o sangue pelo organismo. Isto é, recebe sangue pobre em oxigénio, encaminha-o para os pulmões onde será enriquecido em oxigénio. O sangue enriquecido em oxigénio é então encaminhado novamente para o coração que será enviado para todas as partes do corpo humano. O eletrocardiograma desempenha um papel fundamental de modo a diagnosticar eventuais anomalias no correto funcionamento do coração. Estas anomalias podem dever-se a diversos fatores como tabaco, colesterol, pressão sanguínea alta ou diabetes entre outros. As anomalias associadas ao ritmo cardíaco são denominadas de arritmias. As arritmias são fundamentalmente originadas pela alteração da frequência ou do ritmo cardíaco. Utilizando a lógica difusa, pretendeu-se desenvolver um sistema que fizesse a identificação de um determinado número de tipos de batimentos entre os quais: o bloqueio do ramo esquerdo (LBBB), bloqueio do ramo direito (RBBB), contração prematura ventricular (VPC) e contração prematura auricular (APC). Todos os desenvolvimentos efetuados, a nível de programação, são neste documento relatados de forma a constituírem um possível guia para a utilização deste tipo de sistemas. Mais ainda, descrevem-se nele toda a pesquisa efetuada e as alternativas de desenvolvimento selecionadas. O Sistema de Deteção de Arritmias (SDA) desenvolvido mostrou-se eficaz desde que o utilizador consiga identificar corretamente os parâmetros que lhe são pedidos. A interface gráfica desenvolvida permitiu também uma maior facilidade durante a análise do sinal eletrocardiográfico.

Pancreatic involvement in co-infection visceral leishmaniasis and HIV: histological and ultrastructural aspects

The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.

Expression of cyclooxygenase enzymes and prostaglandin E2 receptors in inflammatory airway diseases

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Quantitative analysis of cardiac lesions in chronic canine chagasic cardiomyopathy

Lesions observed in chronic chagasic cardiopathy frequently produce electrocardiographic alterations and affect cardiac function. Through a computerized morphometrical analysis we quantified the areas occupied by cardiac muscle, connective and adipose tissues in the right atrium of dogs experimentally infected with Trypanosoma cruzi. All of the infected dogs showed chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis and adipose tissue replacement. In the atrial myocardium of dogs infected with Be78 and Be62 cardiac muscle represented 34 and 50%, fibrosis 28 and 32% and adipose tissue 38 and 18%, respectively. The fibrosis observed was both diffuse and focal and mostly intrafascicular, either partially or completely interrupting the path of muscle bundles. Such histological alterations probably contributed to the appearance of electrocardiographic disturbances verified in 10 out 11 dogs which are also common in human chronic chagasic cardiopathy. Fibrosis was the most important microscopic occurrence found since it produces rearrangements of collagen fibers in relation to myocardiocytes which causes changes in anatomical physiognomy and mechanical behavior of the myocardium. These abnormalities can contribute to the appearance of cardiac malfunction, arrythmias and congestive cardiac insufficiency as observed in two of the analyzed dogs. Strain Be78 caused destruction of atrial cardiac muscle higher than that induced by strain Be62.

The spectrum of computerized tomography (CT) findings in central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii in immunocompetent children

Cranial CT scans of eleven immunocompetent children with central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii were retrospectively reviewed. These children had an average age of 8.8 years and positive culture for C. n. var. gattii in cerebrospinal fluid. The most common signs and symptoms were headache, fever, nuchal rigidity, nausea and vomiting. No normal cranial CT was detected in any patient. Hypodense nodules were observed in all patients . The remaining scan abnormalities were as follows: nine had diffuse atrophy, six had hydrocephalus, and five had hydrocephalus coexistent with diffuse atrophy.

American trypanosomiasis and electrocardiographic alterations among industrial workers in São Paulo, Brazil

In this article, we evaluate electrocardiographic (ECG) alterations among urban workers from a mechanical-metallurgical industry in São Paulo, Brazil. In a cross-sectional survey carried out in 1980, we found 2.2% positive serological testing for Trypanosoma cruzi infection among 27,081 workers. A comparison between seropositive workers and a random sample of seronegative workers frequency-matched by age and occupation revealed that seropositive workers had a much lower educational level, and that a higher proportion of seropositive workers had ECG abnormalities (42.7%) when compared to those negative for T. cruzi infection (19.8%). The high frequency of ECG abnormalities suggests the need to provide medical assistance to these workers, without any kind of discrimination and to bring in a form of management that would decrease this dangerous risk to the workers and people around them.

Aborto recorrente das causas na mulher às consequências para o casal

RESUMO: O aborto recorrente (AR) é um evento extremamente traumático com grande impacto na vida dos casais. Apesar de avanços significativos verificados na investigação médica, cerca de 50% dos casos continua sem uma causa identificada. Alguns aspectos como a caracterização inadequada das doentes e das perdas gestacionais, assim como diferentes metodologias utilizadas no seu estudo, têm influenciado a prevalência de alguns dos factores causais e dificultado a compreensão do AR. Da mesma forma, pouco se sabe sobre as diferenças de género na vivência psicológica do aborto recorrente e das suas eventuais repercussões para o relacionamento do casal, centrando-se os poucos estudos existentes preferencialmente na mulher. Por esta razão, o objectivo desta tese foi a caracterização dos factores médicos associados ao AR e das consequências psicológicas desta entidade, contribuindo para promover estratégias clínicas baseadas na evidência específica. Na primeira parte desta tese (capítulos 1 e 2), após uma breve introdução geral e através de uma revisão da literatura, efectua-se uma reflexão sobre o tema, abordando a epidemiologia do aborto recorrente, os factores médicos e os aspectos psicológicos associados. Nos capítulos 3 e 4 descrevemos três estudos efectuados em mulheres portuguesas com aborto recorrente. O primeiro estudo teve por objectivo caracterizar os factores médicos e determinar o padrão da perda recorrente de gravidez, numa coorte de mulheres submetidas a um protocolo de diagnóstico definido. As participantes foram agrupadas de acordo com a paridade (AR primário ou secundário) e a idade gestacional das perdas (embrionárias ou fetais). As anomalias da cavidade uterina, a SAAF e as translocações equilibradas parentais foram os factores mais prevalentes. 15,6% das participantes eram obesas. Em 55,5% dos casos não foi identificado nenhum factor. A história obstétrica materna influenciou significativamente os resultados encontrados: os factores anatómicos e a SAAF foram mais prevalentes em nulíparas e as perdas inexplicadas foram mais frequentes em mulheres com AR secundário. Assim, os nossos dados reforçam os resultados de pesquisas anteriores sobre a importância da obesidade, da síndrome de anticorpos antifosfolípidos e das anomalias uterinas estruturais como factores associados ao AR e mostram que os a paridade é um moderador da importância desses factores. Capítulo 6 94 A ausência de resultados consensuais na literatura sobre a etiologia do AR condiciona a pesquisa sistemática de alguns factores, envolvendo exames dispendiosos, muitas vezes sem que exista evidência que suporte a sua associação com esta entidade. A trombofilia hereditária é uma das condições frequentemente investigadas nestas doentes. O nosso segundo estudo pretende contribuir para clarificar o papel de duas mutações (factor V Leiden e protrombina G20210A) na perda recorrente de gravidez e esclarecer a necessidade do seu rastreio nestas situações. Foi efectuada a pesquisa destes polimorfismos em 100 mulheres com AR inexplicado e num grupo de controlo de multíparas sem história de perdas de gravidez. Na nossa amostra não se verificou uma associação entre perdas embrionárias recorrentes e estas mutações. Nas mulheres com este tipo de perdas, a prevalência do FLV foi inclusive menor do que a verificada nos controlos. Pelo contrário, nas participantes com perdas fetais a prevalência destes polimorfismos foi muito superior à verificada nos controlos, sugerindo uma possível associação entre estas duas entidades. A pequena dimensão deste último subgrupo de mulheres, não nos permitiu contudo tirar conclusões. Uma investigação prospectiva multicêntrica é necessária antes de recomendar a pesquisa da trombofilia hereditária na investigação do AR. Procurámos incluir também nesta tese uma dimensão psicológica e contribuir assim para o conhecimento dos processos relacionais originados pelo AR. No terceiro estudo foram investigadas as diferenças de género na vivência do AR e o seu impacto no relacionamento e sexualidade do casal. Participaram neste estudo 30 casais sem filhos, com pelo menos 3 abortos espontâneos consecutivos. Cada membro do casal respondeu a um conjunto de questionários (Impact of Events Scale, Perinatal Grief Scale, Partnership Questionnaire e Intimate Relationship Scale). Os resultados mostram que as mulheres sofrem mais intensamente do que os homens com o AR, relacionando-se a intensidade do seu sofrimento com a qualidade do relacionamento conjugal. A sexualidade do casal é também afectada pelo stress e pelo sofrimento associados ao AR. Uma avaliação e acompanhamento deste tipo de problemas são imprescindíveis para ajudar estes casais a manterem a qualidade afectiva e sexual da sua relação. Finalmente, no capítulo 5 sumariámos as conclusões de toda a contribuição pessoal para a investigação sobre os factores associados e repercussões para o casal da perda recorrente de gravidez.-------------------ABSTRACT: Recurrent miscarriage (RM), a rare condition, has been described as a traumatic event for couples. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with RM. However, despite significant advances in medical research, the vast majority of cases remain unexplained. Aspects as the ethnic diversity of the population with different expression of genes, the inappropriate characterization of patients and of pregnancy losses, as well as different methodologies used in their study, have influenced the prevalence of etiological factors and have hampered the understanding of this problem. Similarly, little is known about gender differences in psychological experience of RM and its implications for the relationship of the couple. The first objective of this thesis is the characterization of the medical factors and of the psychological consequences related with RM, in the Portuguese population, helping to promote specific evidence-based clinical strategies. In the first part of this thesis, and after a brief general introduction (Chapter 1), a critical review of literature on the definition, the epidemiology and the dimensions involved, with a special emphasis on associated medical and psychological aspects of recurrent miscarriage, is presented (Chapter 2). In Chapters 3 and 4 we describe three studies carried out in Portuguese couples with RM. The first study aimed to investigate the etiological factors and the pattern of pregnancy loss in a cohort of women with RM. Subjects were divided in groups according to their parity (primary or secondary RM) and time of pregnancy loss (embryonic or fetal). Parental chromosome anomalies, uterine anomalies and antiphospholipid syndrome were the most prevalent medical factors. 15.6% of the women were obese. In the majority of cases (55.5%) no identifiable cause was detected. Parity influenced significantly our results. There was a higher prevalence of anatomic factors and antiphospholipid syndrome in primary RM. On the other hand, unexplained losses were more frequent in secondary RM. Except for the parental chromosomal abnormalities; the frequency of risk factors was similar among women with fetal or embryonic losses. Our data emphasizes the results of previous research on the importance of obesity, antiphospholipid syndrome and structural uterine abnormalities as known risk factors for RM, and shows that parity is an important moderator of the weight of those risk factors. Our second study aims to clarify the role of two mutations (factor V Leiden and prothrombin G20210A) and elucidate the need for their screening in Portuguese women with RM. FVL and PT G20210A analysis was carried out in 100 women with three or more consecutive miscarriages and a control group of 100 parous controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal loss). Overall the prevalence of FVL and PT G20210A was similar in RM women compared with controls. In the RM embryonic subgroup of women, FVL prevalence was inclusively lower than that of controls. Conversely in women with fetal losses both polymorphisms were much more frequent, although statistical significance was not reached due to the small size of this subgroup of patients. These data indicate that inherited maternal thrombophilia is not associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with RM and a negative personal history of thromboembolic.96 Our second study aims to clarify the role of two mutations (factor V Leiden and prothrombin G20210A) and elucidate the need for their screening in Portuguese women with RM. FVL and PT G20210A analysis was carried out in 100 women with three or more consecutive miscarriages and a control group of 100 parous controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal loss). Overall the prevalence of FVL and PT G20210A was similar in RM women compared with controls. In the RM embryonic subgroup of women, FVL prevalence was inclusively lower than that of controls. Conversely in women with fetal losses both polymorphisms were much more frequent, although statistical significance was not reached due to the small size of this subgroup of patients. These data indicate that inherited maternal thrombophilia is not associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with RM and a negative personal history of thromboembolic. In our third study, we investigate gender differences in RM experience and its impact on the couple's relationship and sexuality. Each member of 30 couples with RM answered a set of questionnaires, including the Impact of Events Scale (Horowitz et al., 1979), the Perinatal Grief Scale (Toedter et al., 1988), the Partnership Questionnaire (Hahlweg, 1979) and the Intimate Relationship Scale (Hetherington e Soeken, 1990). Results showed that men do grieve, but less intensely than women. Although the quality of the couple‟s relationship seemed not to be adversely affected by RM, both partners described sexual changes after those events. Grief was related to the quality of communication in the couple for women, and to the quality of sex life for men. An understanding of such issues is critical in helping these couples to maintain sexual and affective quality of their relationship. Finally, in Chapter 5, conclusions and clinical implications of all personal contribution to the investigation on associated factors and relational consequences of recurrent miscarriage are presented.