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Apheresis technology has progressed significantly over the last 50-60 years from a predominately blood donation–based procedure to one that now includes a variety of therapeutic modalities. The last 25 years also has seen an increase in the number of diseases treated by therapeutic apheresis (TA) modalities. Because of ethical considerations, therapeutic modalities are often vetted first in adult populations before establishing utility in pediatric patients. TA is no different. The majority of published studies involve adult patients. Pediatric apheresis studies are traditionally retrospective, single-center experiences, single case reports, or case series. To confirm this, we evaluated the peer-reviewed published literature to assess the level of evidence of clinical pediatric apheresis studies published in the last 21 years. Adverse events experienced by pediatric patients undergoing TA procedures and procedural modifications necessary to accommodate pediatric patients receiving TA were also explored. Consideration was given to differences in disease outcomes in pediatric vs adult patients and evolution of TA treatment indications. A systematic search of the literature yielded >1000 pediatric apheresis publications. Only 370 articles specifically assessed TA in the treatment of a pediatric disease. Of those, the majority (98%) were single-center experiences, single case reports, or case series. The remaining 2% were prospective cohort studies or randomized controlled trials. This first formal assessment of the pediatric apheresis literature confirms the findings of previous anecdotal reports and expert opinion. [ABSTRACT FROM AUTHOR]

Abstract: Lack of efficacy and safety data among Chinese patients with stroke have contributed to the slow development of stroke thrombolysis as standard-of-care for these patients. We examined a retrospective cohort of 57 patients who received intravenous alteplase for acute ischemic stroke to identify predictors of outcome, including age, stroke severity, onset-to-treatment time, and early ischemic changes on brain CT scan. Overall, the mean National Institute of Health Stroke Scale (NIHSS) score was 15.7 and the mean onset-to-treatment time was 142minutes. Twenty-nine (51%) patients had a favorable outcome with modified Rankin Scale (mRS) score of ⩽2 at three months. Ten (17.5%) patients were deceased at three months. Four (7%) patients developed symptomatic intracranial hemorrhage (sICH). For patients aged >80years (n =18), five (28%) achieved favorable outcome, six (33%) were deceased at three months and three (17%) had sICH. Prognosis was worst for patients with NIHSS score >25 (n =5); one (20%) was dependent (mRS 4) and the other four (80%) were deceased. Multivariate analysis found that the Alberta Stroke Program Early CT Score (ASPECTS) was associated with favorable outcome (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1–3.0), and mortality (OR 0.5, 95% CI 0.3–0.9). Our findings showed advanced age and severe stroke were associated with less favorable outcome in Chinese patients receiving intravenous alteplase, ASPECTS can be used reliably to identify patients at risk of poor outcomes. Further studies are warranted. [Copyright &y& Elsevier]

Objective: To describe the clinical and molecular findings of a female carrier of a new mutation in the choroideremia (CHM) gene.Design: Single interventional case report.Methods: A 27-year-old woman was seen with mild difficulties with dark adaptation and a history of a retinal degeneration in her father and choroideremia in 3 male paternal first cousins. Visual acuity measurements, peripheral and color vision tests, electroretinography (ERG), Goldmann visual fields, fluorescein angiogram, computed tomography scan, and DNA analysis were performed.Main outcome measures: (1) Visual fields, (2) fluorescein angiography, and (3) DNA analysis.Results: Visual acuity decreased from 20/30 to 10/200 in the right eye abruptly over 2 months, then remained stable over 2 years of follow-up and remained 20/25 in the left eye. Goldmann visual fields showed development of a central scotoma in the right eye concurrent with the rapid decline. A small amount of subretinal hemorrhage was visible on dilated fundus examination at that time, but definite leakage was not evident on fluorescein angiography; afterwards, a choroidal neovascular membrane (CNV) was suspected. The ERG was normal. DNA analysis revealed that the patient was heterozygous for a previously undescribed substitution mutation at the 3′-splice site of intron 6 of the CHM gene (850–1 G to C), confirmed by mRNA analysis with reverse transcriptase polymerase chain reaction.Conclusions: Severe visual acuity loss rarely occurs in female carriers of choroideremia mutations. The diagnosis should be considered in patients with a suitable family history and fundus findings. Physicians should consider the possibility of CNV development in such patients, which may be a response to abnormal retinal pigment epithelium. Recognition of this new mutation may help identify patients who could benefit from current and future treatments to protect against vision loss. [Copyright &y& Elsevier]

Copper(II) and zinc(II) complexes of cross-bridged cyclam and cyclen with primary amide pendant arms (ligands 1 and 2) have been prepared and structurally characterized. The copper complex of cyclam-derived 1 has a Jahn–Teller distorted Cu(II) octahedral coordination geometry with both amide arms coordinated through the carbonyl oxygens. The Cu(II) complex of the cyclen analogue 2 has been found to exist in three slightly different forms. Both zinc complexes also adopt full N4O2 coordination from these potentially hexadentate cross-bridged ligands. These structural data confirm the exclusive cis-folded ligand configuration in all four complexes as well as the significantly better fit of ligand 1 towards both Cu(II) and Zn(II) cations when compared to 2. The complexes of 1 provide the first examples of a [2233]/[2233] cross-bridged cyclam conformation, as opposed to the previously observed [2323]/[2323] conformation. [Copyright &y& Elsevier]

We report on the development and implementation of a robust algorithm for extracting text in digitized color video. The algorithm first computes maximum gradient difference to detect potential text line segments from horizontal scan lines of the video. Potential text line segments are then expanded or combined with potential text line segments from adjacent scan lines to form text blocks, which are then subject to filtering and refinement. Color information is then used to more precisely locate text pixels within the detected text blocks. The robustness of the algorithm is demonstrated by using a variety of color images digitized from broadcast television for testing. The algorithm also performs well on images after JPEG compression and decompression, and on images corrupted with different types of noise. [Copyright &y& Elsevier]

Gallium(III) and indium(III) complexes of cross-bridged cyclam and cyclen tetraaza macrocyclic ligands have been prepared and structurally characterized. In the crystalline state, both the GaCl3 (cross-bridged cyclam) and InBr3 (cross-bridged cyclen) complexes feature hexacoordinate cations in cis-folded tetradentate ligand clefts with ancillary cis-dihalides. These represent the first well-characterized gallium and indium halide complexes of tetraazamacrocycles. [Copyright &y& Elsevier]

Crystallographic structures of Cu(II) complexes of the 18N6 macrocyclic ligand show tetragonal distortions in the mer- conformers, but not their fac -counterparts, due to a dynamic Jahn-Teller effect in the latter; DFT calculations corroborate this interpretation and provide a plausible mechanism for facile mer-fac isomerization. [Display omitted] The syntheses and crystal structures of mer - and fac -isomers of [Cu(18N6)]2+(X−) 2 are reported (18 N6 = 1,4,7,10,13,16-hexaazacyclooctadecane; X− = BF 4 −, ClO 4 −, NO 3 −) and compared to a previously reported example (X− = Cl−). Solution structures of the [Cu(18N6)]2+ dication in MeNO 2 or MeOH are shown by FT-IR to be almost exclusively mer , and simple evaporation of these solutions or crystallization using Et 2 O co-solvent also afford the solid mer -salts. However, using C 6 H 6 or CCl 4 as crystallization co-solvents afforded the corresponding fac -isomers of the BF 4 − and ClO 4 − salts, in which the anions and the symmetrical solvent occupy locations on the crystallographic 3-fold axis. Similar treatment of the less symmetrical NO 3 − salts affords the mer- isomer without inclusion of C 6 H 6. The solid-state structures of the mer -isomers each exhibit the anticipated tetragonal Jahn-Teller distortions, with two longer Cu-N bonds. In contrast the fac -isomers all show internally identical Cu-N distances, due to a dynamic exchange between Jahn-Teller distorted structures in the crystal. Density Functional Theory (DFT) is used to provide rationalizations of these observations and to elucidate an energetically feasible mechanistic pathway for the facile interconversion of mer and fac isomers in solution. [ABSTRACT FROM AUTHOR]

Apheresis Medicine is a medical discipline that involves a variety of procedures (based on the targeted component to be removed or collected), indications (therapeutic vs. donation), and personnel (operators, management, and medical oversight). Apheresis services are accredited and/or regulated by a number of agencies and organizations. Given the complexity and the heterogeneity of apheresis services, it has been particularly challenging to formulate educational goals and define curriculums that easily cover all aspects of Apheresis Medicine. This review summarizes the current state of the discipline in the United States of America, and some of the challenges, strategies, and resources that Apheresis Medicine educators have used to ensure that Apheresis Medicine educational programs meet the health care needs of the relevant population within regulatory and accrediting entity frameworks. [ABSTRACT FROM AUTHOR]

Abstract: The cross-bridged tetraamine ligand 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A) allows formation of a radio-copper complex with higher in vivo stability than that of the corresponding non-cross-bridged analog 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). The structure of the natCu(II) complex of CB-TE2A has been previously determined by X-ray crystallography; however, direct high-pressure liquid chromatography (HPLC) characterization of the corresponding 64Cu complex was inaccessible due to the inability to detect the complex by ultraviolet absorbance at the radiotracer level. A reverse-phase HPLC separation of a series of natCu(II)-tetraazamacrocyclic complexes, both traditional and cross-bridged, was developed and applied toward characterization and assessment of the purity of the corresponding no-carrier-added 64Cu-labeled complexes. Verification of the identity of copper-64-labeled compounds was also achieved by coupling this HPLC method with mass spectrometry. The radio-liquid chromatography/mass spectrometry methodology was further extended to study the in vivo metabolic fates of 64Cu-azamacrocyclic complexes. [Copyright &y& Elsevier]