Avaliação do volume e índices vasculares placentários pela ultrassonografia tridimensional em gestações com restrição grave de crescimento fetal

INTRODUÇÃO: A restrição de crescimento fetal (RCF) representa uma das principais complicações da gravidez e está associada a elevadas taxas de morbimortalidade perinatal. A frequência de desfechos desfavoráveis neonatais está diretamente relacionada à gravidade da RCF, sendo que os casos de pior evolução estão relacionados com peso abaixo do percentil 3. O mecanismo do crescimento fetal não está totalmente esclarecido, mas resulta da interação entre potencial genético de crescimento e fatores placentários, maternos e ambientais. Dentre os fatores etiológicos, o desenvolvimento anormal da placenta e a diminuição da perfusão uteroplacentária são as principais causas de RCF. Este estudo teve por objetivo avaliar volume e índices de vascularização placentários, por meio da ultrassonografia tridimensional (US3D), em gestações com RCF grave, e as correlações dos parâmetros placentários com valores de normalidade e dopplervelocimetria materno-fetal. MÉTODOS: Foram avaliadas 27 gestantes cujos fetos apresentavam peso estimado abaixo do percentil 3 para a idade gestacional. Por meio da US3D, utilizando-se a técnica VOCAL, foram mensurados o volume placentário (VP) e os índices vasculares: índice de vascularização (IV), índice de fluxo (IF) e índice de vascularização e fluxo (IVF). Os dados foram comparados com a curva de normalidade para a idade gestacional e peso fetal descrita por De Paula e cols. (2008, 2009). Desde que os volumes placentários variam durante a gravidez, os valores observados foram comparados com os valores esperados para a idade gestacional e peso fetal. Foram criados os índices volume observado/ esperado para a idade gestacional (Vo/e IG) e volume placentário observado/ esperado para o peso fetal (Vo/e PF). Os parâmetros placentários foram correlacionados com índice de pulsatilidade (IP) médio de (AUt) e IP de artéria umbilical (AU), e avaliados segundo a presença de incisura protodiastólica bilateral em AUt. RESULTADOS: Quando comparadas à curva de normalidade, as placentas de gestação com RCF grave apresentaram VP, IV, IF e IVF significativamente menores (p < 0,0001 para todos os parâmetros). Houve correlação inversa estatisticamente significante da média do PI de AUt com o Vo/e IG (r= -0,461, p= 0,018), IV (r= -0,401, p= 0,042) e IVF (r= -0,421, p= 0,048). No grupo de gestantes que apresentavam incisura protodiastólica bilateral de artérias uterinas, Vo/e IG (p= 0,014), Vo/e PF (p= 0,02) e IV (p= 0,044) foram significativamente mais baixos. Nenhum dos parâmetros placentários apresentou correlação significativa com IP de AU. CONCLUSÕES: Observou-se que o volume e os índices de vascularização placentários apresentam-se diminuídos nos fetos com RCF grave. IP médio de AUT apresenta correlação negativa com Vo/e IG, IV e IVF, e Vo/e IG, Vo/e PF e IV apresentaram-se reduzidos nos casos de incisura bilateral. Não houve correlação significativa dos parâmetros placentários com IP de AU

Factor VIII deficiency inhibition or abnormal contact

Poster presented at the International Society on Thrombosis and Haemostasis 2015 Congress, 20-25 June 2015, Toronto.

Von Willebrand Disease: be or not to be, that is the question

Poster presented at the International Society on Thrombosis and Haemostasis 2015 Congress, 20-25 June 2015, Toronto.

Pontosubicular apoptosis ("necrosis") in human neonates with intrauterine growth retardation and placental infarction

In a previous study of 37 autopsied stillbirths with non-dysmorphic intrauterine growth retardation ( IUGR), 26 cases were associated with placental infarction, a morphologic marker of uteroplacental insufficiency. Nine of the 26 cases with both IUGR and placental infarction, where archival tissue was available, had grey matter ischaemic lesions that were subsequently identified as pontosubicular necrosis. This lesion is now regarded as a localized form of apoptosis. A further eight third trimester stillbirth cases with both IUGR and placental infarction were ascertained prospectively. Sixteen of these 17 cases showed pontosubicular apoptosis, identified morphologically and verified using activated caspase-3 and TUNEL. Five of the 17 cases showed apoptosis in the frontal or temporal cortex as well. In this current study, pontosubicular apoptosis was strongly associated with IUGR and placental infarction in third trimester stillborns, suggesting that uteroplacental insufficiency leading to chronic fetal hypoxaemia may cause cerebral apoptosis.

Diagnosis of canine bleeding disorders

Canine bleeding disorders arise due to a multitude of conditions and require detailed clinical and laboratory investigation. A productive diagnostic approach depends on a thorough patient history, physical examination, haemostatic screening tests and an array of specific diagnostic tests. Patient history is necessary to assist determination of the onset, severity and possible aetiologies of a bleeding disorder. Similarly, a complete physical examination should ideally allow differentiation between disorders of primary and secondary haemostasis. Following this distinction, a variety of laboratory tests are indicated to further define the nature of the bleeding episode. These tests may be broadly categorised as screening tests of primary haemostasis, secondary haemostasis and fibrinolysis, and specific tests directed at identifying particular disorders. Appropriate utilisation of these tests and interpretation of their results in conjunction with patient signalment, history and clinical signs affords the greatest chance of a successful diagnosis.

Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis

Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis.

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

Psychological influence of the media on patients commencing oral anticoagulation in atrial fibrillation:a qualitative analysis

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF); however it is still underutilized and sometimes refused by patients. Two inter-related studies were undertaken to understand the experiences and what influences this un- derutilisation of warfarin treatment in AF patients. These studies explored physician and patient experiences of AF and OAC treatment. The paper focuses on specific sub-themes from the study that explored patients’ experiences will be discussed. Aim: The study in question aimed to explore the experiences which influence patients’ decisions to accept, decline or discontinue OAC. Methods: Semi-structured individual interviews with patients were con- ducted. Three sub-groups of patients (n = 11) diagnosed with AF were interviewed; those who accepted, refused, and who discontinued war- farin. Interpretative phenomenological analysis (IPA) was used to examine the data. IPA is a qualitative method that focuses on how participants make sense of an experiences phenomenon Results: Three over-arching themes comprised patients’ experiences: (i)the initial consultation, (ii) life after the consultation, and (iii) patients’reflections. In the last theme, patients reflected on their perceptions ofaspirin and warfarin. Aspirin was perceived as a natural wonder-drugwhile warfarin was perceived as a dangerous drug usually given to peo-ple at the end of their life. Interestingly they perceive both drugs as‘old’. However, for aspirin it had a positive association, old meaningtried and tested. While for warfarin, old meant ‘has been around fortoo long’.Conclusion: Media had an important role in how patients’ perceptionsof these two drugs were influenced. Literature shows that framingtechniques, i.e. using certain words or phrases such as ‘rat poison’, areprocesses adopted by media to alter medical knowledge into lay per-son’s language. Patients in turn form negative cognitive schemas,between the word ‘poison’ and warfarin, leading to the negative per-ception of warfarin which could influence non-adherence to treatment.This qualitative research highlighted the potential influences of themedia on AF patient perceptions commencing OAC treatment. Theassociation between media stimuli and patient perceptions on OACshould be further explored. The influential power of lay-media couldalso be instrumental in disseminating appropriate educational materialto the public

The experiences of con sultations on oral anticoagula-tion for AF:the importance of qualitative research incardiovascular sciences

Objectives: Multiple-perspective qualitative designs can aid researchersto develop a more multifaceted account of a phenomenon and as aform of triangulation of data. Two interlinking studies aimed toexplore patients’ and physicians’ experiences of atrial fibrillation (AF)and warfarin.Methods: Audio-recorded semistructured individual interviews wereused. Study 1: Three AF patient subgroups were interviewed (n = 11);accepted, refused, or discontinued warfarin. Study 2: Four physiciansubgroups (n = 16): consultant cardiologists, consultant general physi-cians, general practitioners, and cardiology registrars. Data was ana-lyzed using interpretative phenomenological analysis, a qualitativemethodology.Results: Study 1: Three overarching themes comprised patients’ experi-ences: the initial consultation, life after the consultation, and patients’reflections. Patients commented on the reassurance experienced duringthe consultation, but they perceived the decision-making processmostly led by the physician. Lack of education and take-home materi-als during the initial consultation were highlighted. Patients’ uptake ofinformation was influenced by past experiences and knowledge ofstroke and/or bleeding. Study 2: Two overarching themes covered phy-sicians’ experiences: communicating information and challenges withwarfarin prescription for AF. Physicians’ approach to the consultationstyle shifted through a continuum of compliance-adherence-concor-dance during the consultation. Time and the perceived patient trust inthem as the expert led to physicians to adopt a paternalistic approach.Guideline adherence and the need to adopt a multidisciplinaryapproach were pointed out as current challenges.Conclusion: There is a need to target patients’ and physicians’ abilityto communicate with each other in a comprehensible way. This projecthas illustrated the benefit of using a qualitative approach to under-stand the lived experience of the physician–patient consultation.Disclosure of Interest: None declare

Polyphosphate as a haemostatic modulator

Funding This work was supported by the British Heart Foundation [grant number FS/11/2/28579]. © 2016 Authors; published by Portland Press Limited.

Novel P(3HB) Composite Films Containing Bioactive Glass Nanoparticles for Wound Healing Applications

Bioactive glass (BG) is considered an ideal material for haemostasis as it releases Ca2+ ions upon hydration, which is required to support thrombosis. In this study the effect of the presence of the BG nanoparticles in P(3HB) microsphere films on the structural properties, thermal properties and biocompatibility of the films were studied. The nanoscaled bioactive glass with a high surface area was also tested for its in vitro haemostatic efficacy and was found to be able to successfully reduce the clot detection time. In an effort to study the effect of the roughness induced by the formation of HA on the cellular functions such as cell adhesion, cell mobility and cell differentiation, the composite films were immersed in SBF for a period of 1, 3 and 7 days. From the SEM images the surface of the P(3HB)/n-BG composite microsphere films appeared fairly uniform and smooth on day 1, however on day 3 and day 7 a rough and uneven surface was observed. The presence of HA on the composite microsphere films on day 3 and day 7 influenced the surface roughness of the films. However, when the P(3HB)/n-BG composite microspheres with enhanced surface roughness were tested for biocompatibility, reduced amount of protein adsorption and cell adhesion were observed. This study thus revealed that there is an optimal surface roughness for the P(3HB) microsphere films for increased cell adhesion, beyond which it could be deleterious for cell adhesion and differentiation.

Risk factors in reoperative thyroid surgery for recurrent goitre. Our experience

Aim. Reoperative thyroid surgery is an uncommon operation associated with a higher complication rate; we reviewed our series of patients on whom reoperative thyroid surgery was performed.Method. 106 patients had a thyroid reoperation for recurrent multinodular goiter (93 patients), recurrent thyrotoxicosis (3) or suspected malignancy (10); bilateral completion thyroidectomy was performed in 68 cases, lobectomy in 36, removal of a mediastinal recurrence and of a pyramidal remnant in 1 patient respectively. Results. Temporary hypoparathyroidism occurred in 41 patients (38.67%), definitive in 7 (6.6%), transient recurrent laryngeal nerve palsy in 5 (4.71%), permanent nerve palsy in 1 (0.94%); in 3 cases (2.83%) surgical revision of haemostasis was necessary for postoperative haemorrhage. After monolateral surgery we had 13 cases of transient hypoparathyroidism (34.21%), 2 of definitive (5.26%) and 1 transient recurrent laryngeal nerve palsy (2.63%); after bilateral surgery we had 29 cases of transient hypoparathyroidism (42.64%), 5 of definitive (7.35%), 4 of transient recurrent laryngeal nerve palsy (5.88%), 1 of definitive (1.47%) and 3 of postoperative bleeding (4.41%). Conclusions. Reoperative thyroid surgery is a technical challenge with a high incidence of complications. Scarring, edema and friability of the tissues together with distortion of the landmarks make reoperative surgery azardous. A higher risk of complications is described when previous surgery has been performed on both sides. Total thyroidectomy should be considered the procedure of choice for benign multinodular goiter eliminating the potential of a reoperation. Whenever necessary, reoperative hyroidectomy may be performed safely with little morbidity in experienced hands.

Isolamento e caracterização biológica e bioquímica de um activador do factor x da coagulação presente no veneno da serpente Bothrops erythromelas

Dissertação de Mestrado Integrado em Medicina Veterinária