Assessment of Confirmed Clinical Hypersensitivity to Rituximab in Patients Affected with B-Cell Neoplasia.

Rituximab hypersensitivity reactions are rare but are one of the main causes of rituximab elimination from antilymphoma immunochemotherapy treatments. While the clinical picture may be indistinguishable from other infusion-related reactions, hypersensitivity reactions (HSR) do not disappear and instead become more intense with subsequent administrations. Objective. To describe the use of the 12-step protocol for desensitization to intravenous rituximab in clinical practice and the complementary study of a possible IgE-mediated HSR in the context of B-cell lymphoma treatment. Methods. A 12-step rituximab desensitization protocol was performed prospectively within clinical practice in 10 patients with a history of severe infusion reactions or in patients who had a repeated reaction at subsequent doses despite taking more intense preventive measures. Skin prick tests were performed at the time of reaction and at a later time to eliminate false negatives due to possible drug interference. Results. Overall, with the desensitization protocol, 70% of patients were able to complete the scheduled immunochemotherapy. Two patients had to discontinue the therapy due to clinical persistence and the third due to lymphoma progression. Intradermal tests with 0.1% rituximab were positive in only 20% of cases, demonstrating a mechanism of hypersensitivity. Conclusions. The 12-step desensitization protocol is very effective and assumable within healthcare practice. There is a need to determine the mechanism underlying the infusion reaction in a large proportion of cases due to the risk of future drug exposure.

Age-related changes in posture control are differentially affected by postural and cognitive task complexity.

The simple postural task of quiet standing, which requires minimal attentional resources, is generally paired with cognitive activity. Competition for attentional resources is a consequence of simultaneously performing balance tasks and cognitive tasks, and impairment of attentional resource allocation with aging leads to increased risks of fall. We investigated age-related changes in posture control during dual task performance, using a paradigm that crossed a static (quiet standing) and a dynamic (keeping balance on a translational force plate) postural task and cognitive tasks of low demand (mental arithmetic) and high demand (spatial memory). Postural performance was analyzed through center-of-pressure displacements using both statistical (body sway area/sway velocity) and nonlinear (wavelet transform) methods in three age groups (younger, middle-aged, and older healthy participants). Results showed that 1) the nonlinear analysis method was more sensitive than the traditional approach in distinguishing performance between age groups, a result that explains discrepancies in the dual-task literature; 2) dual-tasking costs were dependent on both postural task difficulty and cognitive task complexity, corroborating previous investigations; 3) younger adults improved their postural performance during dual-tasking, but older adults lowered their performance; 4) balance recovery strategies in the dynamic postural task appeared to differ in younger versus older adults. Together, our findings on dual-tasking can be interpreted within the conceptual frame of task prioritization: shifting attention away from postural task automates posture control in the younger adults, whereas prioritization of postural task and selection of compensatory strategy are the main characteristics of posture control in the older population.

Polyunsaturated fatty acid deficiency during dietary treatment of very long-chain acyl-CoA dehydrogenase deficiency. Rescue with soybean oil.

Nutritional management of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is based on the avoidance of fasting and substitution of medium-chain triglycerides for long- and very long-chain triglycerides. We report two cases of this disease, which developed omega-6 essential fatty acid deficiency after three and five months from the beginning of nutritional therapy (SHS product: Monogen). This alteration could be especially dangerous in these patients owing to their possible susceptibility to the development of pigmentary retinopathy. The incorporation of linoleic acid as 3-4% of total caloric intake supported as soybean oil ameliorates this deficiency. We wish to remark on this early complication in the nutritional management of VLCAD deficiency and the possibility of rescue by the incorporation of soybean oil into the diet.

Ab Initio MRCI Calculation and Modeling of the A1Pi Potential Energy Curve of CO.

We report a MRCI study of the A1Pi potential energy curve of CO. The calculated ab initio energies are analytically modeled using the EHFACE2 and RKHS methods. A barrier of approximately 730 cm-1 is predicted at an internuclear distance of approximately 4.2a0 in agreement with previous calculations and spectroscopic measurements. The origin of such a barrier is briefly discussed. Copyright 1998 Academic Press.

A comparative study by a single chromatographic procedure of glycolytic regulatory kinase isozymes in rat erythroid cells as a function of differentiation-maturation process.

The isozymes of three glycolytic regulatory kinases: hexokinase, phosphofructokinase and pyruvate kinase are fractionated by a single ion exchange chromatographic procedure on DEAE-cellulose. Enriched-erythroblast bone marrow cells showed two heterogeneous peaks, each consisting of two overlapping peaks: one major and one minor peak, but only two isozymes were observed in reticulocytes and erythrocytes. Phosphofructokinase showed multiple isozymic forms in the three cell populations, but while in erythroblasts the main one eluted in the last fractions, in reticulocytes and erythrocytes it eluted in the early fractions. Pyruvate kinase showed a main early activity peak with a shoulder in erythroblasts, reticulocytes and erythrocytes but the response to the allosteric effectors (fructose-1,6-bisphosphate and ATP) suggests the presence of different pyruvate kinase isozymes in reticulocytes and erythrocytes.

Evaluation of five immunoassays for the determination of digoxin in serum.

Five immunoassays for the determination of digoxin have been evaluated (Digoxin II, Abbott; Cedia Digoxin XL, Microgenics; Coat-a-Count Digoxin, Diagnostic Procedure Corporation, DPC; "On-line" Digoxin, Roche Diagnostic Systems; EMIT 2000 Digoxin, Syva). Four of them required no sample pre-treatment. The methods included a radioimmunoassay, fluoroimmunoassay, two enzyme-immunoassays and a turbidimetric immunoassay: the last three mentioned were adapted to the Cobas Mira Plus. The intra- and inter-assay precision was lower than 9%, except for Microgenics. The calibration stability fluctuated from 120 days for Abbott to 27 days for the Roche test, 7 days for the Syva assay and 2 days for Microgenics. The DPC test was not assayed for calibration stability. The interference from "digoxin-like immunoreactive factor(s)" differed according to the assay. The highest interference was seen with Abbott and Microgenics, and the lowest with the DPC test. The comparison among all the methods offered values of "r" higher than 0.95 except Microgenics and Syva assays where "r" was 0.896. The results obtained with Roche and Microgenics were higher than 12% of the remaining assays.

Surface properties of crosslinked erythrocytes as studied by counter-current distribution in aqueous polymer two-phase systems.

The bifunctional imidoester dimethyl suberimidate hydrochloride can stabilize rat red blood cells (RBCs) by membrane protein crosslinking, and in that way they can be used as carrier systems for exogenous substances. Counter-current distribution fractionation in charge-sensitive dextran-polyethyleneglycol two-phase systems has been used to detect slight changes in surface charge in stabilized cells. A decrease in the surface charge of crosslinked RBCs and an apparent masking of the age-related cell surface properties have been found to result from the protein crosslinking. Digitonin treatment used to permeabilize crosslinked RBCs produces a significant decrease of the cell surface charge while the age-related surface properties do not seem to be modified by the treatment.

Biochemical characterization of human erythrocytes fractionated by counter-current distribution in aqueous polymer two-phase systems.

The fractionation of normal human erythrocytes by counter-current distribution (CCD) in charge-sensitive dextran-polyethylene glycol two-phase systems was confirmed and extended to red blood cells from heterozygous beta-thalassaemic patients. The differences between the distribution profiles of normal (homogeneous) and abnormal (heterogeneous) red blood cells reflect their different surface-charge properties. As suggested by the decline of membrane sialic acid released after neuraminidase treatment and the specific activities of two age-dependent enzymes (membrane acetylcholinesterase and intracellular pyruvate kinase) in the distribution profiles (from the left- to the right-hand side fractions), the fractionation seems to be according to red blood cell age. A constancy of the 2,3-bisphosphoglycerate level was observed in ageing red blood cells.

Changes in glycolytic enzyme activities in aging erythrocytes fractionated by counter-current distribution in aqueous polymer two-phase systems.

Human and rat erythrocytes were fractionated by counter-current distribution in charge-sensitive dextran/poly(ethylene glycol) two-phase systems. The specific activities of the key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase) declined along the distribution profiles, although the relative positions of the activity profiles were reversed in the two species. These enzymes maintained their normal response to specific regulatory effectors in all cell fractions. No variations were observed for phosphoglycerate kinase and bisphosphoglycerate mutase activities. Some correlations between enzyme activities (pyruvate kinase/hexokinase, pyruvate kinase/phosphofructokinase, pyruvate kinase/pyruvate kinase plus phosphoglycerate kinase, pyruvate kinase/bisphosphoglycerate mutase and phosphoglycerate kinase/bisphosphoglycerate mutase ratios) were studied in whole erythrocyte populations as well as in cell fractions. These results strongly support the fractionation of human erythrocytes according to cell age, as occurs with rat erythrocytes.

Fractionation in two-phase systems of red cells during rat development: changes in pyruvate kinase and bisphosphoglycerate mutase activities in relation to red cell switching.

An inverse relationship between 2,3-bisphosphoglycerate levels and the ratio calculated from pyruvate kinase and bisphosphoglycerate mutase activities has been observed in red populations of rats during animal development. Counter-current distribution in aqueous two-phase systems of these cells populations shows a displacement of distribution profiles towards the high-numbered cavities of the rotor as animal ages. Heterogeneity of cells after distribution is only observed during the switching process from fetal to adult red cells taking place along the postnatal stage of development. Values for the pyruvate kinase/bisphosphoglycerate mutase ratio in these fractions suggest the separation of fetal (liver) from adult (bone marrow) red cells.