179 research outputs found

    An Athlete With Bicuspid Aortic Valve Regurgitation and Left Ventricular Dilatation: A Clinical Conundrum.

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    The physiologic cardiac adaptations caused by intensive exercise and the pathophysiologic changes caused by significant regurgitant valvular lesions can be challenging to differentiate. We describe the clinical course of an asymptomatic 31-year-old elite triathlete with a moderately regurgitant bicuspid aortic valve and severe left ventricular and aortic dilatation. (Level of Difficulty: Intermediate.)

    Strategic crossing of biomass and harvest index—source and sink—achieves genetic gains in wheat

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    To accelerate genetic gains in breeding, physiological trait (PT) characterization of candidate parents can help make more strategic crosses, increasing the probability of accumulating favorable alleles compared to crossing relatively uncharacterized lines. In this study, crosses were designed to complement “source” with “sink” traits, where at least one parent was selected for favorable expression of biomass and/or radiation use efficiency—source—and the other for sink-related traits like harvest-index, kernel weight and grains per spike. Female parents were selected from among genetic resources—including landraces and products of wide-crossing (i.e. synthetic wheat)—that had been evaluated in Mexico at high yield potential or under heat stress, while elite lines were used as males. Progeny of crosses were advanced to the F4 generation within Mexico, and F4-derived F5 and F6 generations were yield tested to populate four international nurseries, targeted to high yield environments (2nd and 3rd WYCYT) for yield potential, and heat stressed environments (2nd and 4th SATYN) for climate resilience, respectively. Each nursery was grown as multi-location yield trials. Genetic gains were achieved in both temperate and hot environments, with most new PT-derived lines expressing superior yield and biomass compared to local checks at almost all international sites. Furthermore, the tendency across all four nurseries indicated either the superiority of the best new PT lines compared with the CIMMYT elite checks, or the superiority of all new PT lines as a group compared with all checks, and in some cases, both. Results support—in a realistic breeding context—the hypothesis that yield and radiation use efficiency can be increased by improving source:sink balance, and validate the feasibility of incorporating exotic germplasm into mainstream breeding efforts to accelerate genetic gains for yield potential and climate resilience

    Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

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    <p>Abstract</p> <p>Background</p> <p>Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs.</p> <p>Methods</p> <p>19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS) was evaluated by Real Time-PCR.</p> <p>Results</p> <p>Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p < 0.05) but not in the aorta. Endothelial dysfunction was apparent at 3 months of exposure and did not increase further after 6 months of exposure. Smoke-exposed animals showed proliferation of poorly differentiated smooth muscle cells in small vessels (p < 0.05) after 3 months of exposure. Prolonged exposure resulted in full muscularization of small pulmonary vessels (p < 0.05), wall thickening (p < 0.01) and increased contractility of the main pulmonary artery (p < 0.05), and enlargement of the alveolar spaces. Lung expression of eNOS was decreased in animals exposed to cigarette smoke.</p> <p>Conclusion</p> <p>In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.</p

    Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution

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    An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex

    Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

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    We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n=8), laryngeal dysplasia (n=10) and laryngeal squamous cell carcinoma (n=10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (ρ=0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P=0.001), Ki67 (P=0.0002), cyclin D1 (P=0.015), cyclin A (P=0.0001) and cyclin B1 (P=0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia

    Coronary artery anomalies and the role of echocardiography in pre-participation screening of athletes: a practical guide.

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    Transthoracic echocardiography is an essential and widely available diagnostic tool for assessing individuals reporting cardiovascular symptoms, monitoring those with established cardiac conditions and for preparticipation screening of athletes. While its use is well-defined in hospital and clinic settings, echocardiography is increasingly being utilised in the community, including in the rapidly expanding sub-speciality of sports cardiology. There is, however, a knowledge and practical gap in the challenging area of the assessment of coronary artery anomalies, which is an important cause of sudden cardiac death, often in asymptomatic athletic individuals. To address this, we present a step-by-step guide to facilitate the recognition and assessment of anomalous coronary arteries using transthoracic echocardiography at the bedside; whilst recognising the importance of performing dedicated cross-sectional imaging, specifically coronary computed tomography (CTCA) where clinically indicated on a case-by-case basis. This guide is intended to be useful for echocardiographers and physicians in their routine clinical practice whilst recognising that echocardiography remains a highly skill-dependent technique that relies on expertise at the bedside

    Coronary artery anomalies and the role of echocardiography in pre-participation screening of athletes: a practical guide

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    Transthoracic echocardiography is an essential and widely available diagnostic tool for assessing individuals reporting cardiovascular symptoms, monitoring those with established cardiac conditions and for preparticipation screening of athletes. While its use is well-defined in hospital and clinic settings, echocardiography is increasingly being utilised in the community, including in the rapidly expanding sub-speciality of sports cardiology. There is, however, a knowledge and practical gap in the challenging area of the assessment of coronary artery anomalies, which is an important cause of sudden cardiac death, often in asymptomatic athletic individuals. To address this, we present a step-by-step guide to facilitate the recognition and assessment of anomalous coronary arteries using transthoracic echocardiography at the bedside; whilst recognising the importance of performing dedicated cross-sectional imaging, specifically coronary computed tomography (CTCA) where clinically indicated on a case-by-case basis. This guide is intended to be useful for echocardiographers and physicians in their routine clinical practice whilst recognising that echocardiography remains a highly skill-dependent technique that relies on expertise at the bedside

    Orthotopic Liver Transplantation in an Adult with Cholesterol Ester Storage Disease

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    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit
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