Publications by authors named "Hugh Leonard"

Article Synopsis
  • Epithelioid hemangioendothelioma (EHE) is difficult to treat with traditional chemotherapy, prompting researchers to explore new therapies such as sirolimus and identify biomarkers for tumor aggressiveness.
  • Scientists created a patient-derived xenograft (PDX) model from an advanced EHE patient to test sirolimus and to study serum levels of Growth/Differentiation Factor 15 (GDF-15) as a potential biomarker.
  • The results indicated sirolimus was more effective than doxorubicin in reducing tumor growth and GDF-15 levels, establishing GDF-15 as a promising biomarker for EHE aggressiveness and potentially indicating the effectiveness of sirolimus in patients.
View Article and Find Full Text PDF
Article Synopsis
  • Epithelioid hemangioendothelioma (EHE) is a rare type of cancer with unique features, but its natural history and best treatment practices are not well understood.
  • The EURACAN project has created a registry to gather prospective data on newly diagnosed EHE patients to enhance understanding of the disease.
  • The study will involve collecting comprehensive patient data from specialized hospitals to identify prognostic factors, treatment efficacy, and to monitor the disease's progression and outcomes over time.
View Article and Find Full Text PDF

Herbivory is a fundamental ecological force in the evolution of plant physiological, morphological, and chemical attributes. In this study, we explored how browsing pressure by local deer populations affected leaf form and function in two California native tree species, Quercus agrifolia (coast live oak) and Umbellularia californica (California bay laurel). Specifically, we investigated how leaf and stem vascular attributes differed between browsed and non-browsed zones of each species.

View Article and Find Full Text PDF

Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.

View Article and Find Full Text PDF

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge.

View Article and Find Full Text PDF

Background: Tissue factor (TF) generates proteases that can signal through PAR-1 and PAR-2. We have previously demonstrated PAR-1 signalling primes innate myeloid cells to be exquisitely sensitive to interferon-gamma (IFNγ). In this work we explored how TF mediated PAR-2 signalling modulated responsiveness to IFNγ and investigated the interplay between PAR-1/-2 signalling on macrophages.

View Article and Find Full Text PDF

Objective: Epithelioid haemangioendothelioma (EHE) is an ultrarare vascular sarcoma with an incidence of <1/million/year and a large clinical heterogeneity. Data on supportive care needs of rare cancer patients are scarce. This study aimed to investigate the level of supportive care needs of EHE patients and its association with sociodemographic, clinical and symptom burden characteristics.

View Article and Find Full Text PDF

The long-term trajectory of kidney function recovery or decline for survivors of critical illness is incompletely understood. Characterising changes in kidney function after critical illness and associated episodes of acute kidney injury (AKI), could inform strategies to monitor and treat new or progressive chronic kidney disease. We assessed changes in estimated glomerular filtration rate (eGFR) and impact of AKI for 1301 critical care survivors with 5291 eGFR measurements (median 3 [IQR 2, 5] per patient) between hospital discharge (2004-2008) and end of 7 years of follow-up.

View Article and Find Full Text PDF

Delayed-type hypersensitivity (DTH) responses underpin chronic inflammation. Using a model of oxazolone-induced dermatitis and a combination of transgenic mice, adoptive cell transfer, and selective agonists/antagonists against protease activated receptors, we show that that PAR-1 signaling on macrophages by thrombin is required for effective granuloma formation. Using BM-derived macrophages (BMMs) , we show that thrombin signaling induced (a) downregulation of cell membrane reverse cholesterol transporter ABCA1 and (b) increased expression of IFNγ receptor and enhanced co-localization within increased areas of cholesterol-rich membrane microdomains.

View Article and Find Full Text PDF

Background Anticoagulants induce atherosclerosis regression in animal models but exploiting this clinically is limited by bleeding events. Here we test a novel thrombin inhibitor, PTL060, comprising hirulog covalently linked to a synthetic myristoyl electrostatic switch to tether to cell membranes. Methods and Results ApoE-/- mice were fed chow or high-fat diets, before transplantation of congenic aortic segments or injection of PTL060, parental hirulog, control saline, or labeled CD11b positive cells.

View Article and Find Full Text PDF

Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with unique clinical features. EHE is characterized by an unpredictable, often protracted, clinical course and highly variable clinical presentation. Due to difficulty recruiting ultra-rare cancer patients, health-related quality of life (HRQoL) of EHE patients has not yet been studied.

View Article and Find Full Text PDF

Severe and life-threatening hypercalcaemia can develop in haemodialysis patients dialysed against a dialysate with a high calcium concentration, the so-called hard water syndrome. Here we describe the development of hard water syndrome in 30 patients following sequential failure of the reverse osmosis unit and water softeners. Serum calcium levels rose from 2.

View Article and Find Full Text PDF

Background: The best approach for surgical treatment of an infected THA remains controversial. Two-stage revision is believed to result in lower reinfection rates but may result in significant functional impairment. Some authors now suggest that single-stage revision may provide comparable results in terms of infection eradication while providing superior functional outcomes.

View Article and Find Full Text PDF