Oxidant stress and the hyperdynamic circulation in portal hypertension

The partial portal vein ligation rat model of portal hypertension is associated with the development of a hyperdynamic circulation characterised by an increased cardiac index and a reduced systemic vascular resistance. Recent studies have shown that tumour necrosis factor-α is involved in the development of the hyperdynamic response. Studies on tumour necrosis factor-α in vitro have shown that the signal transduction pathways involve activation of the transcription factor NF-κB by reactive oxygen species and that this can be inhibited by antioxidants. It is not known however, whether involvement of these pathways can be demonstrated in vivo in this model, and whether treatment with antioxidants can inhibit these signalling pathways and thus the development of the hyperdynamic circulation. This thesis concentrated on the signal transduction pathways and the possible role of oxidant stress in the generation of the hyperdynamic circulation in the partial portal vein ligated rat model compared with sham controls. Firstly, a group of compounds known as the F2-isoprostanes were studied as markers of lipid peroxidation. Secondly, activation of the transcription factor NF-κB was measured in whole liver from different study groups. Levels of plasma TNF-α levels were then measured, as were plasma levels of nitrite and nitrate. Finally, haemodynamic studies were performed in different groups to evaluate the pharmacodynamic effects of different reagents including N-acetylcysteine, pyrrolidine dithiocarbamate and BB-1101. Partial portal vein ligation is associated with increased lipid peroxidation, activation of hepatic NF-κB and increased nitric oxide synthesis. Furthermore, the hyperdynamic circulation can be inhibited by the chronic administration of N-acetylcysteine, pyrrolidine dithiocarbamate and BB-1101 to PPVL rats. The precise mechanism of action of these reagents remains unclear and further work needs to be performed to answer these questions

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics, but not future graft function.

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single-center cohort, we examined the relationship between donor-, recipient-, and transplantation-associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2-3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post-transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post-transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes

Análisis de las percepciones de los profesores de las escuelas de formación de profesores de Benguela y de Lobito en relación a las acciones de formación continua

El objetivo general de esta tesis es analizar las percepciones de los profesores de las escuelas de formación de profesores de Benguela y Lobito en relación a las acciones de formación continua y sus logros, para comprender simultáneamente la importancia que puede llegar a tener la formación continua en la adquisición y desarrollo de competencias y en la mejora de la profesionalización docente. En base a estos supuestos, estructuramos nuestro estudio de la manera que se explicita a continuación. En la primera parte, se comenzó haciendo una conceptualización y definición de los conceptos inherentes al estudio desarrollado, contextualizados en sus respectivos capítulos, considerando necesarias una clarificación. Esto nos ha servido y permitido sustentar el problema de investigación sobre una base teórica sólida. La segunda parte corresponde al diseño metodológico, el cual se compone por la descripción del problema de investigación, la justificación de la investigación, el establecimiento de los objetivos general y específicos, así como la delimitación de la naturaleza de la investigación y los instrumentos de recolección de datos, así como el análisis y tratamiento de los resultados. En la tercera parte se presentarán las conclusiones, referencias bibliográficas, legislación y anexos.Tesis Univ. Granada. Programa Oficial de Doctorado en Currículum, Profesorado e Instituciones Educativa

Abdominal wall hernias:a cross-sectional pictorial review

The classification of abdominal wall hernias is often made difficult by confusing eponymous and anatomic nomenclature. In this article, we review the anatomy that defines the various types of hernias. The specific cross-sectional radiologic features required to correctly identify each type are then emphasized. The appropriate clinical context and the merits of the various imaging techniques available for the investigation of abdominal wall hernias are also discussed

Mobile learning in medicine: an evaluation of attitudes and behaviours of medical students

Abstract Background Mobile learning (mLearning) devices (such as tablets and smartphones) are increasingly part of the clinical environment but there is a limited and somewhat conflicting literature regarding the impact of such devices in the clinical learning environment. This study aims to: assess the impact of mLearning devices in the clinical learning environment on medical students’ studying habits, attitudes towards mobile device supported learning; and the perceived reaction of clinicians and patients to the use of these devices as part of learning in the clinical setting. Methods Over three consecutive academic years, 18 cohorts of medical students (total n = 275) on a six-week rotation at a large teaching hospital in London were supplied with mLearning devices (iPad mini) to support their placement-based learning. Feedback on their experiences and perceptions was collected via pre- and post-use questionnaires. Results The results suggest mLearning devices have a positive effect on the students’ perceived efficiency of working, while experience of usage not only confirmed pre-existing positive opinions about devices but also disputed some expected limitations associated with mLearning devices in the clinical workplace. Students were more likely to use devices in ‘down-time’ than as part of their clinical learning. As anticipated, both by users and from the literature, universal internet access was a major limitation to device use. The results were inconclusive about the student preference for device provision versus supporting a pre-owned device. Conclusion M-learning devices can have a positive impact on the learning experiences medical students during their clinical attachments. The results supported the feasibility of providing mLearning devices to support learning in the clinical environment. However, universal internet is a fundamental limitation to optimal device utilisation

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients.

BACKGROUND & AIMS De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival

Do we need a different organ allocation system for kidney transplants using donors after circulatory death?

There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy