Northwick Park Hospital

About: Northwick Park Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Blood pressure. The organization has 4387 authors who have published 4184 publications receiving 192933 citations.

Long-segment (> or = 10 cm) femoropopliteal angioplasty: improved technical success and long-term patency.

Abstract: PURPOSE: To assess angioplasty as a treatment for symptomatic long-segment (> or = 10 cm) femoropopliteal atherosclerotic disease. MATERIALS AND METHODS: Angioplasty performed on 44 lesions that measured 10-40 cm (mean, 24.3 cm) were assessed for technical success and 12-24-month patency. Disease severity was assessed with the Doppler ankle-brachial index (ABI) and clinical evaluation before angioplasty and at follow-up examinations 1 month and 12-24 months (mean, 18 months) later. Technical success was defined as a restoration of vessel lumen (< 30% residual stenosis) and a rise in ABI values of at least 0.2. Arterial patency (< 50% residual stenosis) was determined with color duplex sonography. RESULTS: Angioplasty was technically successful at 41 of 44 sites (93%). There was no mortality related to the procedure or emergency surgical referral. At 18-month follow-up, mean ABI values had risen from 0.53 to 0.80. Cumulative primary patency was 69%. Clinical symptoms had improved in 83% of patients. CONCLU...

Spectrum of craniosynostosis phenotypes associated with novel mutations at the fibroblast growth factor receptor 2 locus.

Abstract: The causative relationship between several of the syndromic forms of craniosynostosis and mutations in the fibroblast growth factor receptor (FGFR) loci is now well established. However, within the group of patients with craniosynostosis, there are several families and sporadic cases whose clinical features differ in variable degrees from the classically described syndromes of craniosynostosis. In this communication we present novel FGFR2 mutations associated with a spectrum of craniosynostosis phenotypes in 4 sporadic cases and in one family in which craniosynostosis segregates. The mutation and phenotype data presented emphasise the clinical variability of mutations at this locus and underline the plasticity of the phenotype-genotype relationship in this important group of congenital malformation syndromes. Mutations found were tyrosine 105 to cysteine, glycine 338 to glutamic acid, serine 351 to cysteine and glycine 384 to arginine. These are the first reported mutations in the first immunoglobulin-like loop (tyrosine 105 to cysteine) and the transmembrane domain (glycine 384 to arginine) of FGFR2, providing further insights into the mechanism of abnormal receptor function in FGFR2 mutations.

Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging

Abstract: Aims To determine if perfusion stress echocardiography (PSE) with Imagify™ (perflubutane polymer microspheres) is comparable to stress perfusion imaging using 99mTc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD. Methods and results Chronic, stable, chest pain patients ( n = 662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha = 0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66–71%, P ≤ 0.004). Four demonstrated non-inferior sensitivity (68–77%, P ≤ 0.002), three demonstrated non-inferior specificity (72–88%, P ≤ 0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment. Conclusions Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging.

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

Abstract: Background: Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. Methodology/Principal Findings: MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. Conclusions: These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

Time course characterization of serum cardiac troponins, heart fatty acid - Binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat

Abstract: We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.