Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate

Elevated serum phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperphosphatemia, and in general treatment with oral phosphate binding agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients. Treatment of hyperphosphatemia with standard calcium-based phosphate binders and vitamin D compounds can induce hypercalcemic episodes, increase the Ca × PO4 product and thus add to the risk of ectopic mineralization. In this review, recent clinical as well as experimental data on lanthanum carbonate, a novel, non-calcium, non-resin phosphate binding agent are summarized. Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium. Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up. The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics

Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia–reperfusion

INTRODUCTION: Beside lung transplantation, cardiopulmonary bypass, isolated lung perfusion and sleeve resection result in serious pulmonary ischemia–reperfusion injury, clinically known as acute respiratory distress syndrome. Very little is known about cells infiltrating the lung during ischemia–reperfusion. Therefore, a model of warm ischemia–reperfusion injury was applied to differentiate cellular infiltrates and to quantify tissue damage. METHODS: Fifty rats were randomized into eight groups. Five groups underwent warm ischemia for 60 min followed by 30 min and 1–4 hours of warm reperfusion. An additional group was flushed with the use of isolated lung perfusion after 4 hours of reperfusion. One of two sham groups was also flushed. Neutrophils and oedema were investigated by using samples processed with hematoxylin/eosin stain at a magnification of ×500. Immunohistochemistry with antibody ED-1 (magnification ×250) and antibody 1F4 (magnification ×400) was applied to visualize macrophages and T cells. TdT-mediated dUTP nick end labelling was used for detecting apoptosis. Statistical significance was accepted at P < 0.05. RESULTS: Neutrophils were increased after 30 min until 4 hours of reperfusion as well as after flushing. A doubling in number of macrophages and a fourfold increase in T cells were observed after 30 min until 1 and 2 hours of reperfusion, respectively. Apoptosis with significant oedema in the absence of necrosis was seen after 30 min to 4 hours of reperfusion. CONCLUSIONS: After warm ischemia–reperfusion a significant increase in infiltration of neutrophils, T cells and macrophages was observed. This study showed apoptosis with serious oedema in the absence of necrosis after all periods of reperfusion

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments.

Immunotargeting of PLAP-expressing tumours was studied for two radioiodinated, highly specific anti-PLAP monoclonal antibodies, 7E8 and 17E3, differing 10-fold in affinity, as well as for 7E8 F(ab')2 fragments. An anti-CEA monoclonal antibody or anti-CD3 F(ab')2 fragments were used as controls. Specific and non-specific targeting was examined in nude mice simultaneously grafted with PLAP-positive tumours derived from MO4 1-4 cells, and CEA-positive tumours, derived from 5583-S cells. Results indicated that (1) MO4 1-4 tumours, with a stable expression of PLAP on the plasma membrane, represent a useful new in vivo model for immunodirected tumour targeting; (2) differences in antibody affinity for PLAP in vitro are not reflected in antibody avidity for tumour cells in vivo; and (3) excellent selective and specific localisation of the PLAP-positive tumours is achieved when 7E8 F(ab')2 fragments are used. The high tumour/blood ratios (10.7 +/- 3.9 at 46 h after injection) were due to a much faster blood clearance of 7E8 F(ab')2 fragments. At this time point, the mean tumour/non-tumour tissue ratio was as high as 34.5, and the mean specific localisation index was 29.0. As expected, the F(ab')2 fragments provided high tumour imaging efficiency on gamma camera recording. These data imply important potentials of the PLAP/anti-PLAP system for immunolocalisation and therapy in patients, but also emphasise that in vitro criteria alone are not reflected in in vivo tumour localisation capacities of antibodies

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Complexity of global semianalytic sets in a real analytic manifold of dimension 2

Let X subset of R-n be a real analytic manifold of dimension 2. We study the stability index of X, s(X), that is the smallest integer s such that any basic open subset of X can be written using s global analytic functions. We show that s(X) = 2 as it happens in the semialgebraic case. Also, we prove that the Hormander-Lojasiewicz inequality and the Finiteness Theorem hold true in this context. Finally, we compute the stability index for basic closed subsets, S, and the invariants t and (t) over bar for the number of unions of open (resp. closed) basic sets required to describe any open (resp. closed) global semianalytic set

Augmented versus Virtual Reality Laparoscopic Simulation: What Is the Difference?: A Comparison of the ProMIS Augmented Reality Laparoscopic Simulator versus LapSim Virtual Reality Laparoscopic Simulator

BACKGROUND: Virtual reality (VR) is an emerging new modality for laparoscopic skills training; however, most simulators lack realistic haptic feedback. Augmented reality (AR) is a new laparoscopic simulation system offering a combination of physical objects and VR simulation. Laparoscopic instruments are used within an hybrid mannequin on tissue or objects while using video tracking. This study was designed to assess the difference in realism, haptic feedback, and didactic value between AR and VR laparoscopic simulation. METHODS: The ProMIS AR and LapSim VR simulators were used in this study. The participants performed a basic skills task and a suturing task on both simulators, after which they filled out a questionnaire about their demographics and their opinion of both simulators scored on a 5-point Likert scale. The participants were allotted to 3 groups depending on their experience: experts, intermediates and novices. Significant differences were calculated with the paired t-test. RESULTS: There was general consensus in all groups that the ProMIS AR laparoscopic simulator is more realistic than the LapSim VR laparoscopic simulator in both the basic skills task (mean 4.22 resp. 2.18, P <0.000) as well as the suturing task (mean 4.15 resp. 1.85, P <0.000). The ProMIS is regarded as having better haptic feedback (mean 3.92 resp. 1.92, P <0.000) and as being more useful for training surgical residents (mean 4.51 resp. 2.94, P <0.000). CONCLUSIONS: In comparison with the VR simulator, the AR laparoscopic simulator was regarded by all participants as a better simulator for laparoscopic skills training on all tested feature

Reliability of retinal vessel calibre measurements using a retinal oximeter

Background: Summarised retinal vessel diameters are linked to systemic vascular pathology. Monochromatic images provide best contrast to measure vessel calibres. However, when obtaining images with a dual wavelength oximeter the red-free image can be extracted as the green channel information only which in turn will reduce the number of photographs taken at a given time. This will reduce patient exposure to the camera flash and could provide sufficient quality images to reliably measure vessel calibres. Methods: We obtained retinal images of one eye of 45 healthy participants. Central retinal arteriolar and central retinal venular equivalents (CRAE and CRVE, respectively) were measured using semi-automated software from two monochromatic images: one taken with a red-free filter and one extracted from the green channel of a dual wavelength oximetry image. Results: Participants were aged between 21 and 62 years, all were normotensive (SBP: 115 (12) mmHg; DBP: 72 (10) mmHg) and had normal intra-ocular pressures (12 (3) mmHg). Bland-Altman analysis revealed good agreement of CRAE and CRVE as obtained from both images (mean bias CRAE = 0.88; CRVE = 2.82). Conclusions: Summarised retinal vessel calibre measurements obtained from oximetry images are in good agreement to those obtained using red-free photographs