No description available.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 6 uppsatser.

Rationnel: Bien qu'elles constituent la majorité des thromboses veineuses des membres inférieurs, les thromboses veineuses profondes (TVP) distale et les thromboses veineuses superficielles (TVS) ont été peu étudiées et leur significativité clinique et leur prise en charge sont débattues.Méthodes: Cette thèse collige les résultats des travaux effectués par J.P. Galanaud sur les TVP distales et les TVS à partir des études épidémiologiques OPTIMEV, POST et RIETE.Résultats commentés: TVP distale: La TVP distale n'a pas le même profil de facteur de risque que la TVP proximale. Sa mortalité associée à court terme est plus faible que celle des TVP proximales mais supérieure à celle de témoins confirmant qu'il s'agit d'une entité cliniquement significative. Les différences de profil de population et de complications entre ces deux types de TVP suggèrent que le rapport bénéfice/risque du traitement anticoagulant est différent. Il n'est donc pas légitime d'extrapoler les résultats des essais des TVP proximales aux TVP distales. Des essais spécifiques sont donc nécessaires.TVS: En cas de TVS le risque de TVP concomitante est élevé. Un examen écho-doppler doit être réalisé et devra au moins explorer l'ensemble du réseau profond du membre inférieur affecté. Sexe masculin et antécédents de TVP/Embolie pulmonaire constituent des facteurs prédictifs indépendants de récidive. Si certaines TVS peuvent être traitées avec succès sans traitement anticoagulant, celles associées à un cancer ou à une atteinte saphéno-fémorale sont à haut risque de récidive y compris après un traitement anticoagulant curatif. / Background: Though they represent the majority of all lower limbs thromboses, isolated distal deep-vein thrombosis (DVT) (without symptomatic pulmonary embolism (PE)) and isolated superficial vein thrombosis (SVT) (without DVT or PE) have been poorly studied. Their clinical significance and management are under debate.Methods: Data from epidemiological multicenter prospective studies OPTIMEV, POST, RIETEResults and comments: Isolated distal DVT: Distal and proximal DVTs exhibit a different risk factor profile, the latter being more associated with chronic risk factors. Three-month mortality of distal DVT patient is lower than that of proximal DVT ones but is higher than that of controls. This evidences that distal DVT is a clinically significant finding. Differences in population profile and outcomes suggests that the benefit/risk ratio of anticoagulant treatment is not similar. Data from proximal DVT clinical trials should no longer be extrapolated to distal DVT.Isolated SVT: In case of SVT the risk of concomitant DVT is high. A compression ultrasonographic exam should be performed and at least explore the whole deep venous system of the affected limb. Male gender and history of DVT/Pulmonary embolism are independent predicators of recurrence. Some SVT can be safely treated without anticoagulants. On contrary, in patients with cancer or a sapheno-femoral junction involvement, the risk of deep venous recurrence is high even upon full therapeutic dose of anticoagulants.

El Potato yellow vein virus (PYVV) es un Crinivirus perteneciente a la Familia Closteroviridae, el cual reduce la producción total de papa en América del Sur hasta un 50%. La detección visual de los cultivos es una práctica habitual, pero la enfermedad generalmente se detecta después de que se ha producido un daño significativo a los tejidos fotosintéticos. A través de técnicas de teledetección se puede evaluar el estado nutricional y fitosanitario de las plantas, detectando incidencias de plagas y enfermedades e inferir posibles carencias nutricionales. Con el objetivo de detectar la infección de PYVV en cultivos de papa antes de la aparición de los síntomas visuales se empleó la técnica de teledetección, mediante el uso del espectroradiómetro. Se llevaron a cabo 5 experimentos, empleando 5 variedades de papa: Única, Clon W.A., Canchan INIA, Amarillis y Costanera. La infección con PYVV fue inducida mediante injerto lateral. Se tomaron 3 mediciones espectroradiométricas por cada planta 2 veces por semana durante todo el periodo de observación y se realizó una evaluación visual continua de los síntomas. Asimismo, se confirmó la presencia del virus PYVV mediante RT-PCR. Finalmente, se evaluó el rendimiento de las 5 variedades y se identificó la variedad más susceptible al virus. Se pudo hacer un diagnóstico precoz de la infección por PYVV en las 5 variedades de papa. La variedad Canchan INIA se detectó entre 8 y 14 días antes de la aparición de los síntomas visuales, Única entre 7 y 18 días, Costanera entre 12 y 17 días, Amarillis entre 6 y 12 días, y finalmente Clon W.A. se pudo detectar entre 2 y 11 días antes de la aparición de los síntomas. La variedad Canchan INIA fue la variedad más susceptible al virus, ya que presentó el mayor porcentaje de reducción en el rendimiento, con un 36.63%, seguido de Costanera y Amarillis con un 28.57% y 28.31%, respectivamente. Clon W.A. fue la variedad menos afectada en cuando a la reducción en el rendimiento, con un 6.67%.Potato yellow vein virus (PYVV) is a Crinivirus belonging to the Closteroviridae Family, which reduces the total potato production in South America up to 50%. Visual detection of cultures is a common practice, but the disease is usually detected after significant damage to photosynthetic tissues has occurred. Through remote sensing techniques, it is possible to evaluate the nutritional and phytosanitary status of plants, detecting pest and disease incidences and inferring possible nutritional deficiencies. In order to detect PYVV infection in potato cultures before the appearance of visual symptoms, the technique of remote sensing was used, using the spectroradiometer. Five experiments were carried out, using 5 varieties of potato: Única, Clon W.A., Canchan INIA, Amarillis and Costanera. Infection with PYVV was induced by lateral grafting. Three spectroradiometric measurements were taken per plant 2 times per week throughout the observation period and a continuous visual evaluation of the symptoms was performed. Also, the presence of the PYVV virus was confirmed by RT-PCR. Finally, the yield of the 5 varieties was evaluated and the variety more susceptible to the virus was identified. An early diagnosis of PYVV infection could be made in all 5 potato varieties. Canchan INIA variety was detected between 8 and 14 days before the appearance of visual symptoms, Unica between 7 and 18 days, Costanera between 12 and 17 days, Amarillis between 6 and 12 days, and finally Clon W.A. could be detected between 2 and 11 days before the onset of symptoms. Canchan INIA variety was the most susceptible to the virus, as it presented the highest percentage reduction in yield, with 36.63%, followed by Costanera and Amarillis with 28.57% and 28.31%, respectively. Clon W.A. was the least affected variety when compared to the reduction in yield, with 6.67%.

Análise da expressão de neurotrofinas durante a regeneração de nervo periférico de rato por enxerto venoso Enxertos de veias têm sido empregados para preencher lacunas em nervos periféricos transeccionados para melhor recuperação funcional. No entanto, vários inconvenientes, como a constrição do enxerto secundário foram observados. Uma nova alternativa para esta técnica foi desenvolvida. Simplesmente invertendo a veia de dentro para fora, chamado do Inside- out vein graft. As neurotrofinas são uma família de fatores neurotróficos conhecidos por desempenhar um papel significativo na regeneração de nervos periféricos. A família da neurotrofina é constituído por fator de crescimento nervoso (NGF), fator neurotrófico derivado do cérebro (BDNF), Neurotrofina-3 (NT-3) e Neurotrofina-4 (NT-4). No campo da neurobiologia, vários autores têm utilizado a técnica de PCR a fim de obter mais informações sobre os nervos regenerados. Neste estudo, foi utilizada a técnica de biologia molecular para explorar o papel e o nível das neurotrofinas durante a regeneração de nervos periféricos com enxerto de veia. O nervo isquiático de ratos foi seccionado e reparado com enxerto de veia invertida (IOVG) e técnicas de enxerto de veia padrão (SVG). No grupo controle, os ratos foram operados e o nervo isquiático foi mantido intacto. Os animais foram sacrificados após 6 e 12 semanas e os enxertos foram colhidos para observar o nível das neurotrofinas. Músculos EDL e Sóleo foram excisados e pesados para determinar a diferença de peso entre os grupos. Um pequeno segmento dos cotos distais de ambos os grupos SVG e IOVG também foram excisados e foram processados histologicamente para examinar a quantidade de axónios regenerados. Além disso, um outro pequeno segmento do coto distal foi processado para RT-PCR para analisar o nível das neurotrofinas nesta área.A tecnica do walk track analysis foi realizada para determinar o índice funcional do nervo isquiático nos grupos. Em 6 semanas, não ocorreu crescimento neuronal significativo no coto distal dos dois tipos de enxertos, porém um crescimento foi observado em 12 semanas. Não houve diferença significativa na massa muscular entre IOVG e SVG em ambos os períodos de tempo. No entanto, um aumento significativo na massa muscular foi observado a partir de 6 a 12 semanas nos grupos IOVG e SVG. Um aumento significativo na produção de NT-3 foi observado no grupo de SVG em ambos, enxerto e o coto distal quando comparados a partir de 6 a 12 semanas, no entanto, não houve aumento observado no nível de neurotrofinas dos outros tipos (NGF e NT-4) . Surpreendentemente, não houve aumento significativo da NT-3 no grupo IOVG. Conclui-se que, entre as neurotrofinas avaliadas neste estudo, não há nenhuma diferença significativa no seu nível de RNAm entre os dois grupos, exceto NT-3. Finalmente, uma vez que o nível de RNAm de NT-3 aumenta significativamente entre 6 e 12 semanas no grupo SVG e não no IOVG, observado por estas duas técnicas de nível molecular, estudos adicionais necessitam serem feitos para decifrar o mecanismo exato. / Vein grafts have been employed to bridge the gap in transected peripheral nerves to produce better functional recovery. However several disadvantages such as secondary graft constriction were observed and a new alternative to this technique was developed by simply reversing the vein inside out. Both inside out and standard vein grafts were successfully used in recovering the sensory segmental defect in humans. Neurotrophins are a family of eurotrophic factors known to play an important role in the regeneration of peripheral nerves. The neurotrophin family consists of Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3) and Neurotropinh-4 (NT-4). In the neurobiology field, several authors have been using PCR technique in order to gain more information regarding regenerated nerves. In this study, we employed this molecular biology technique to explore the role and level of the neurotrophins during the peripheral nerve regeneration with vein graft. The sciatic nerve of rats were sectioned and repaired with Inside out vein graft (IOVG) and standard vein graft techniques (SVG). In the control group the rats were sham operated wherein the sciatic nerve was kept intact. The animals were euthanized at 6 and 12 weeks and the grafts were harvested to observe the level the neurotrophins. EDL and Sol muscles were excised and measured to determine any weight difference between the groups. A small segment of the distal stumps from both the SVG and IOVG groups were also excised and were subjected to histological process to examine the amount of regenerated axon. In addition, another small segment of the distal stump was processed for RT-PCR to further examine the level of the neurotrophins in this area. At 6 weeks, no significant neuronal growth was observed in the distal stump of both graft types but a distinct growth was seen at 12 weeks. Walk track analysis showed poor motor function recovery in the experimental groups during both time intervals. Morphometric analysis demonstrated no significant differences in the amount of myelination between both the groups. There was no significant difference in the muscle mass between IOVG and SVG in both time periods. However, a significant increase in both the muscle mass was observed from 6 to 12 weeks in the IOVG and SVG groups. A significant increase in the production of NT-3 was observed in SVG group in both the distal stump and graft segment when compared from 6 to 12 weeks; however there was no observed increase in the level of other neurotrophins (NGF and NT-4). Surprisingly, no significant increase of NT-3 was noticed in the IOVG group. We conclude that amongst the neurotrophins evaluated in this study, there is no significant difference in their mRNA level between both groups except NT-3. Also, since mRNA level of NT-3 increases significantly between 6 and 12 weeks in SVG and not in IOVG, it suggests that the mechanism by which these two techniques operate at a molecular level may differ and further studies need to be done to decipher the exact mechanism.

Diana.sobieraj@hhchealth.org / Objective To systematically review the literature and to quantitatively evaluate the efficacy and safety of extended pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA). Methods A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, through September 2014) and searching of reference lists of included studies and relevant reviews was conducted to identify randomized controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding). A random-effects Frequentist approach to NMA was used to calculate relative risks with 95% confidence intervals. Results Ten trials (n=11,079) were included. Risk of bias (assessed with the Cochrane tool) was low in most domains assessed across the included trials. Apixaban (2.5mg and 5mg), dabigatran, rivaroxaban, idraparinux and vitamin K antagonists (VKA) each significantly reduced the risk of VTE recurrence compared to placebo, ranging from a 73% reduction with idraparinux to 86% with VKAs. With exception of idraparinux, all active therapies significantly reduced VTE recurrence risk versus aspirin, ranging from a 73% reduction with either apixaban 2.5mg or rivaroxaban to 80% with VKAs. Apixaban and aspirin were the only therapies that did not increase composite bleeding risk significantly compared to placebo. All active therapies except aspirin increased risk of composite bleeding by 2 to 4-fold compared to apixaban 2.5mg, with no difference found between the two apixaban doses. Conclusion Extended treatment of VTE is a reasonable approach to provide continued protection from VTE recurrence although bleeding risk is variable across therapeutic options. Our results indicate that apixaban, dabigatran, rivaroxaban, idraparinux and VKAs all reduced VTE recurrence when compared to placebo. Apixaban appears to have a more favorable safety profile compared to other therapies. / Revisión por pares

The C₄ biochemical pathway is the most efficient form of photosynthesis in warm environments and introducing this system into globally significant, but less efficient, C₃ photosynthetic crops could bring major yield increases. The most photosynthetically efficient C₄ grass species have a specialised leaf anatomy characterised by high vein density with two distinct cell types radially arranged around the vascular bundles (Kranz anatomy). Although this anatomy was first described in 1882, the genetic regulators controlling Kranz development are still not known. In recent years, transcriptomic analysis has allowed researchers to identify candidate Kranz regulator genes, and a model for Kranz development has been proposed, however, this model has not been experimentally validated. This study used in situ hybridisation to visualise expression patterns for a set of candidate Kranz regulator genes in maize and the orthologous genes in rice. Further, morphological analysis of rice lines with constitutive expression of the candidate Kranz regulator genes AINTEGUMENTA 1 and DAG-LIKE 1 and 2 were used to characterise protein function during C₃ monocot leaf development. The function of maize AINTEGUMENTA in the C₃ eudicot arabidopsis was also investigated. The results of the in situ hybridisation experiments led to the refinement of the Kranz model and identified potential roles for the candidate regulators during leaf development. The constitutive expression experiments highlighted the regulatory differences between eudicot and monocot leaf development and implicated the regulation of auxin-cytokinin homeostatis as a key factor in Kranz development. Ultimately, this work can be used to guide research into Kranz development and has direct implications for engineering C₄ photosynthesis into rice.

Background: Myocardial failure and dysfunction is not uncommon during critical illness and following cardiac surgery. For optimal treatment, a better understanding of the effects of inotropic drugs is needed. In this thesis, two non-adrenergic mediated inotropes, milrinone and levosimendan were studied in different models of myocardial dysfunction. The study aims were to assess the following: the effects of milrinone on blood flow in coronary artery bypass grafts during CABG surgery; the effects of milrinone on left ventricular diastolic function during post-ischaemic myocardial dysfunction; whether milrinone or levosimendan are protective or injurious during acute myocardial ischaemia, and if levosimendan potentiates myocardial function when added to milrinone in an experimental model of post-ischaemic (stunned) myocardium. Material and Methods: In Study I, 44 patients undergoing coronary artery bypass surgery(CABG) were included as subjects. Milrinone or saline was administrated in a single dose during cardio-pulmonary bypass (CPB) and coronary graft flow measurements were recorded after 10 and 30 min following CPB. In Study II; 24 patients undergoing CABG had estimations of peak ventricular filling rates made before and after CPB with administration of milrinone or saline as a single dose during CPB, performed by assessment of the rate of change in diastolic cross-sectional left ventricular area. In Study III, energy-metabolic effects of milrinone and levosimendan were measured in an anaesthetized porcine model during 45 minutes of regional myocardial ischemia. Microdialysis sampling of metabolites of local ischemic metabolism allowed assessment of glycolytic activity and the degree of myocardial calcium overload. In Study IV, in a porcine model of postischaemic myocardial stunning, ventricular pressure-volume relationships were analyzed when milrinone or a combination of milrinone and levosimendan were given together. Results: In Study I, there was a clear increase in non-sequential saphenous vein graft blood flow with milrinone at 10 minutes (64.5 ± 37.4 compared to placebo 43.6 ± 25.7 ml/min (mean ± SD).). A decreasing but still measureable flow increase was seen for milrinone at 30 minutes. In Study II, an increase in early left ventricular filling rate (ventricular cross-sectional area rate of change,dA/dt) was seen in the milrinone treated group. Pre-bypass milrinone group dA/dt 22.0 ± 9.5 changed to post-bypass values dA/dt 27.8 ± 11.5 cm2/sec). Placebo group pre-bypass dA/dt was 21.0 ± 8.7 and post-bypass 17.1 ± 7.1 cm2/sec. A milrinone effect was demonstrated in an adjusted regression model (p = 0.001). In Study III, neither milrinone nor levosimendan led to a change in energy-metabolic activity during ischemia as reflected by interstitial glucose, pyruvate, lactate orglycerol. Neither drug exacerbated the relative myocardial calcium overload during ischemia. In Study IV, milrinone improved active relaxation (tau) in post-ischemic stunned myocardium, but did not markedly improve systolic function by preload recruitable stroke work. Levosimendan added to milrinone showed minimal effect on active relaxation but a positive effect on systolic function in combination with milrinone. Conclusions: We conclude that milrinone treatment leads to an increase in blood flow in newly implanted coronary saphenous vein grafts, and improves ventricular relaxation post-cardiopulmonary bypass. Neither milrinone nor levosimendan, in this porcine model, negatively influence myocardial energy metabolism or calcium overload during acute ischaemia. Addition of levosimendan to milrinone treatment during post-ischaemic ventricular dysfunction may provide additive inotropic effects on systolic function but probably not for active relaxation.

This thesis describes the successful development and initial evaluation of a proof-of-concept wireless monitoring system for improving the effectiveness and safety of pneumatic compression therapy to help prevent deep vein thrombosis (DVT). In the development, an important objective was to make feasible the practical and commercial deployment of such improved therapy systems in future, by focusing on a cost-effective design and implementation. Over the years, pneumatic compression has been shown to be an effective solution for the prevention of DVT. However, different problems and complications related to the use of commercial pneumatic compression de-vices that typically include automatic pressure controllers and pneumatic compression sleeves have been reported. For example, one study reported a high percentage of improperly applied or nonfunctional pneumatic compression devices in routine usage. Technical problems, non-compliance, and human error were identified as the causes behind the failed therapies. Also, it was reported that dedicated in-service instruction did not improve the proper use of the pneumatic compression controllers and sleeves. In another study, significant unanticipated variations between expected and delivered pneumatic compression therapy were reported: expected therapy delivered only an average of 77.8% of the time during the therapy, and much of the time key values related to the outcome of the therapy were found to have variations great than 10%. Specific hazards have also been reported. For example, one patient developed acute compartment syndrome after wearing a pair of pneumatic compression sleeves with faulty pressure release valves. In another case, epidural analgesia masked a malfunction resulting from a reversed connection between four-way plastic tubing of the sleeves and the controller, exposing a patient to a hazardous pressure of around 300mmHg,blocking all blood flow for a prolonged period of time. Newer models of pneumatic compression sleeves and controllers from various manufacturers claim to improve therapy by, for example, increasing the peak blood flow velocity. However, there is no evidence in the published literature to support such claims. A published review of the literature from1970-2002 reached the conclusion that the most important factors in im-proving therapy with pneumatic compression devices, particularly during and after surgery, were the degree of conformance of delivered therapy to the prescribed therapy, patient compliance, and the appropriateness of the site of compression. The inability to monitor delivered therapy and patient compliance remains a problem in efforts to improve pneumatic compression therapy. The above-described problems were addressed in the successful development of the innovative prototype described in this thesis. This wireless monitoring system should improve the effectiveness and safety of pneumatic compression therapy. Also, innovative aspects of the system design allow for cost-effective integration into existing commercial controllers and sleeves. For example, an innovative and potentially patentable usage and reprocess indicator was developed for pneumatic compression sleeves to significantly improve their safety and to reduce their cost of use per patient.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成24年3月26日 櫛山泰規氏の博士論文として提出された