The Polish School of Medicine at the University of Edinburgh

The Polish School of Medicine in Edinburgh, 1941–1949, was a unique academic establishment. Although located in Scotland it was governed by Polish academic regulations, conferred Polish degrees and most of the teaching was by Polish academic staff . In this article the author presents the historical background of the School, its activities and its impact on Scottish and Polish medicine.Polska Szkoła Medyczna w Edynburgu w latach 1941–1949 była wyjątkowym ośrodkiem akademickim. Chociaż znajdował się on w Szkocji, podlegał polskim przepisom akademickim, nadawał polskie stopnie naukowe, a większość nauczania prowadzili polscy nauczyciele akademiccy. W artykule autor przedstawia tło historyczne szkoły, jej działalność oraz wpływ na szkocką i polską medycynę

Modification of cardiovascular and renal risk factors using antagonists of the endothelin system

Chronic kidney disease (CKD) is an important independent risk factor in the development of cardiovascular disease (CVD). Indeed, patients with CKD are far more likely to die from CVD than reach end stage renal disease. Conventional cardiovascular risk factors and co-morbidity contribute to this increased risk of CVD. However, emerging evidence suggests other novel factors including inflammation, oxidative stress, and a shift in the balance of the vasodilator nitric oxide and vasoconstrictor endothelin system, are also important contributors. Despite increasing evidence that the endothelin system plays an important role in the development of CKD and CVD, there has been little research examining possible therapeutic benefits of its modification in patients with CKD. The overall aims of the work presented within this thesis were to examine CVD risk in patients with renal impairment and then to see what impact chronic inhibition of the endothelin system would have on risk factors for CVD and CKD progression. In the first two studies I examined markers of arterial stiffness (AS) and endothelial function in a cohort of patients with immune-mediated renal disease. I was able to show in the acute setting that improvement in renal function following treatment for these conditions leads to significant improvements in AS. Interestingly, in patients who were in remission from their renal disease, only classical cardiovascular risk factors appear to be linked to AS. In the next study I was able to prove that sitaxsentan, a selective oral ETA antagonist, did not cause functional blockade of the ETB receptor in man. This was the first study of its kind to confirm that a “selective” endothelin antagonist truly is selective in vivo: a finding that will allow more accurate mechanistic investigation of the ET system. In the final studies, I showed that in subjects with stable non-diabetic proteinuric CKD, chronic selective ETA receptor antagonism reduces blood pressure and AS, and that these systemic benefits are associated with an increase in renal blood flow and reduction in proteinuria. The reduction in proteinuria is most likely haemodynamic and linked to a fall in GFR and filtration fraction, similar to what is seen with ACE inhibitors. Importantly, these benefits were seen in patients already taking maximally tolerated renin-angiotensin aldosterone system blockade, suggesting that chronic endothelin antagonism could be an important future therapy in the management of CKD. In summary, I have shown that renal impairment can directly affect markers of arterial function and by inference increase the risk of CVD. Chronic antagonism of the endothelin system with ETA receptor blockers would appear to improve many of these biomarkers, including reductions in BP, AS and proteinuria. There were no adverse effects reported in these studies, suggesting that selective ETA antagonism may be safe enough for clinical development in CKD patients. Further larger clinical trials are warranted

Calcitonin Gene Peptides: The Diagnostic Value of Measurement in Medullary Thyroid Carcinoma

The calcitonin gene encodes a family of peptides, at least three of which normally circulate in man: calcitonin (CT), a calcium-lowering hormone; katacalcin (KC), a peptide of unknown function; and calcitonin gene-related peptide (CGRP), a neuropeptide and potent vasodilator. In a study of 45 patients with medullary thyroid carcinoma (MTC), plasma CGRP was elevated in approximately 50% of cases. Furthermore, CGRP levels did not correlate with CT levels. However, plasma KC was elevated in all cases, with a good correlation with CT levels, as has been noted previously. Measurement of CT or KC appears to be superior to measurement of CGRP for the detection of MTC

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

<p><b>Background:</b> Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).</p> <p><b>Methods:</b> The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.</p> <p><b>Results:</b> Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.</p> <p><b>Conclusion:</b> Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.</p&gt

Risk Factors for Ovarian Cancer : An Umbrella Review of the Literature

Simple Summary Ovarian cancer is the most lethal cancer of the female genital tract despite major advances in both surgical and oncological treatments. This is in part due to difficulties in identifying those most at risk of developing ovarian cancer, and that there are currently no effective screening strategies. Whilst 20% of cases have a genetic component, the majority have no obvious cause. Many risk factors have been associated with ovarian cancer, although the strength of this evidence remains unclear. This umbrella review attempts to review the validity of associations between non-genetic risk factors and the risk of developing or dying from ovarian cancer. There were six associations that were supported by strong evidence. Greater height, BMI and use of HRT increased the risk, whilst the use of oral contraceptive pill reduced that risk. This review will enable further research into these areas and may promote identification of individuals at high risk. Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11-1.20), body mass index (BMI) (RR >= 30 kg/m(2) versus normal 1.27, 95% CI 1.17-1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69-0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.Peer reviewe

Pheromone-Induced Odor Associative Fear Learning in Rats

Alarm pheromones alert conspecifics to the presence of danger. Can pheromone communication aid in learning specific cues? Such facilitation has an evident evolutionary advantage. We use two associative learning paradigms to test this hypothesis. The first is stressed cage mate-induced conditioning. One pair-housed adult rat received 4 pairings of terpinene + shock over 30 min. Ten minutes after return to the home cage, its companion rat was removed and exposed to terpinene. Single-housed controls were exposed to either terpinene or shock only. Companion rats showed terpinene-specific freezing, which was prevented by β-adrenoceptor blockade. Using Arc to index neuronal activation in response to terpinene re-exposure, stressed cage-mate induced associative learning was measured. Companion rats showed increased neuronal activity in the accessory olfactory bulb, while terpinene + shock-conditioned rats showed increased activity in the main olfactory bulb. Both groups had enhanced activity in the anterior basolateral amygdala and central amygdala. To test involvement of pheromone mediation, in the 2nd paradigm, we paired terpinene with soiled bedding from odor + shock rats or a rat alarm pheromone. Both conditioning increased rats’ freezing to terpinene. Blocking NMDA receptors in the basolateral amygdala prevented odor-specific learning suggesting shock and pheromone-paired pathways converge in the amygdala. An alarm pheromone thus enables cue-specific learning as well as signalling danger