Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure.</p> <p>Methods</p> <p>We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis.</p> <p>Results</p> <p>The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan.</p> <p>Conclusion</p> <p>This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.</p

The Antibacterial Effects of Zinc Ion Migration from Zinc-Based Glass Polyalkenoate Cements

Zinc-based glass polyalkenoate cements have been synthesised and their potential use in orthopaedic applications investigated. Zinc ions were released from the materials in a rapid burst over the first 24 h after synthesis, with the release rate falling below detectable levels after 7 days. Cement-implanted bone samples were prepared, and the released zinc was shown, using energy dispersive X-ray analysis, to penetrate from the cement into the adjacent bone by up to 40 μm. Finally, the cements exhibited antibacterial activity against Streptococcus mutans and Actinomyces viscosus that reflected the pattern of zinc release, with the inhibition of growth greatest shortly after cement synthesis and little or no inhibition measureable after 30 days. © Springer Science + Business Media, LLC 2006

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction

<p>Abstract</p> <p>Background</p> <p>In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.</p> <p>Methods</p> <p>T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.</p> <p>Results</p> <p>At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006).</p> <p>Conclusion</p> <p>In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.</p> <p>Trial registration</p> <p>This trial is registered as NCT00103753</p

Controlled core-to-core photo-polymerisation – fabrication of an optical fibre-based pH sensor

The fabrication of fluorescence-based pH sensors, embedded into etched pits of an optical fibre via highly controllable and spatially selective photo-polymerisation is described and the sensors validated.</p

High Spectral Resolution Observations of the Massive Stars in the Galactic Center

We present high-resolution near-infrared spectra, obtained with the NIRSPEC spectrograph on the W. M. Keck II Telescope, of a collection of hot, massive stars within the central 25 arcseconds of the Galactic center. We have identified a total of twenty-one emission-line stars, seven of which are new radial velocity detections with five of those being classified as He I emission-line stars for the first time. These stars fall into two categories based on their spectral properties: 1) those with narrow 2.112, 2.113 micron He I doublet absorption lines, and 2) those with broad 2.058 micron He I emission lines. These data have the highest spectral resolution ever obtained for these sources and, as a result, both components of the absorption doublet are separately resolved for the first time. We use these spectral features to measure radial velocities. The majority of the measured radial velocities have relative errors of 20 kms, smaller than those previously obtained with proper-motion or radial velocity measurements for similar stellar samples in the Galactic center. The radial velocities estimated from the He I absorption doublet are more robust than those previously estimated from the 2.058 micron emission line, since they do not suffer from confusion due to emission from the surrounding ISM. Using this velocity information, we agree that the stars are orbiting in a somewhat coherent manner but are not as defined into a disk or disks as previously thought. Finally, multi-epoch radial velocity measurements for IRS 16NE show a change in its velocity presumably due to an unseen stellar companion.Comment: ApJ accepted, 42 pages, 16 figure

Bayesian methods outperform parsimony but at the expense of precision in the estimation of phylogeny from discrete morphological data

Different analytical methods can yield competing interpretations of evolutionary history and, currently, there is no definitive method for phylogenetic reconstruction using morphological data. Parsimony has been the primary method for analysing morphological data, but there has been a resurgence of interest in the likelihood-based Mk-model. Here, we test the performance of the Bayesian implementation of the Mk-model relative to both equal and implied-weight implementations of parsimony. Using simulated morphological data, we demonstrate that the Mk-model outperforms equal-weights parsimony in terms of topological accuracy, and implied-weights performs the most poorly. However, the Mk-model produces phylogenies that have less resolution than parsimony methods. This difference in the accuracy and precision of parsimony and Bayesian approaches to topology estimation needs to be considered when selecting a method for phylogeny reconstruction

HST and Spitzer Observations of the HD 207129 Debris Ring

A debris ring around the star HD 207129 (G0V; d = 16.0 pc) has been imaged in scattered visible light with the ACS coronagraph on the Hubble Space Telescope and in thermal emission using MIPS on the Spitzer Space Telescope at 70 microns (resolved) and 160 microns (unresolved). Spitzer IRS (7-35 microns) and MIPS (55-90 microns) spectrographs measured disk emission at >28 microns. In the HST image the disk appears as a ~30 AU wide ring with a mean radius of ~163 AU and is inclined by 60 degrees from pole-on. At 70 microns it appears partially resolved and is elongated in the same direction and with nearly the same size as seen with HST in scattered light. At 0.6 microns the ring shows no significant brightness asymmetry, implying little or no forward scattering by its constituent dust. With a mean surface brightness of V=23.7 mag per square arcsec, it is the faintest disk imaged to date in scattered light.Comment: 28 pages, 8 figure

Presenting features and long-term effects of growth hormone treatment of children with optic nerve hypoplasia/septo-optic dysplasia

<p>Abstract</p> <p>Background</p> <p>Optic nerve hypoplasia (ONH) with/or without septo-optic dysplasia (SOD) is a known concomitant of congenital growth hormone deficiency (CGHD).</p> <p>Methods</p> <p>Demographic and longitudinal data from KIGS, the Pfizer International Growth Database, were compared between 395 subjects with ONH/SOD and CGHD and 158 controls with CGHD without midline pathology.</p> <p>Results</p> <p>ONH/SOD subjects had higher birth length/weight, and mid-parental height SDS. At GH start, height, weight, and BMI SDS were higher in the ONH/SOD group. After 1 year of GH, both groups showed similar changes in height SDS, while weight and BMI SDS remained higher in the ONH/SOD group. The initial height responses of the two groups were similar to those predicted using the KIGS-derived prediction model for children with idiopathic GHD. At near-adult height, ONH/SOD and controls had similar height, weight, and BMI SDS.</p> <p>Conclusions</p> <p>Compared to children with CGHD without midline defects, those with ONH/SOD presented with greater height, weight, and BMI SDS. These differences persisted at 1 year of GH therapy, but appeared to be overcome by long-term GH treatment.</p