Cell fusion was recently reported to account for the plasticity of adult stem cells in vivo. Adult stem cells, referred to as mesenchymal stem cells or marrow stromal cells, from rat marrow, were infused into 1.5-to 2-day-old chick embryos. After 4 days, the rat cells had expanded 1.3-to 33-fold in one-third of surviving embryos. The cells engrafted into many tissues, and no multinuclear cells were detected. The most common site of engraftment was the heart, apparently because the cells were infused just above the dorsal aorta. Some of the cells in the heart expressed cardiotin, and ␣-heavy-chain myosin. GFP ؉ cells reisolated from the embryos had a rat karyotype. Therefore, the cells engrafted and partially differentiated without evidence of cell fusion. Multipotential cells with many of the characteristics of stem cells have now been isolated from a variety of differentiated tissues, including bone marrow, fat, umbilical blood, synovial membranes, brain, and heart (1-14). To varying degrees, the adult stem cells from different sources have been shown to differentiate into a variety of cell phenotypes in culture, including osteoblasts, adipocytes, chondrocytes, epithelial cells, myoblasts, and early precursors of neural cells. Also, a number of investigators have reported that after infusion into animals, adult stem cells from several sources engraft into multiple tissues and, at least in part, differentiate into the phenotype of the cells found in the tissues. Recently, however, several reports have indicated that some or all of the apparent plasticity observed after adult stem cells are administered in vivo is accounted for by the donor cells fusing with recipient cells (15)(16)(17)(18)(19).Among the most extensively studied adult stem cells (1-4, 6, 14, 20) are the cells from bone marrow referred to as mesenchymal stem cells or marrow stromal cells (MSCs). If plated at very low densities, MSCs generate single-cell-derived colonies, and the colonies can be differentiated into several cell phenotypes in culture (1-4, 14, 20). After infusion into irradiated animals, MSCs home to a variety of tissues, particularly after tissue injury (14). Therefore, MSCs and related cells from bone marrow appear to be part of a natural repair system that supplements the stem-like cells found in multiple tissues that are mobilized by tissue injury. Cell fusion by MSCs was recently observed in a coculture system in which MSCs were added to a monolayer of heat-shocked lung epithelial cells. A few of the fused cells also underwent nuclear fusion (21). However, threefourths or more of the MSCs that differentiated into epithelial cells underwent the change in phenotype without evidence of cell fusion (21).In this study, integration and differentiation of rat MSCs were examined in vivo by transplantation into organogenesis-stage embryos. Rat MSCs expressing GFP were grafted in place of epithelial-stage somites of chick embryos that were 1.5-2 days old, i.e., stage 12-13 of development. The grafted cells that survived in the chick ho...

Ever since the introduction of low molecular weight heparins (LMWHs) for clinical use, one of the major questions raised relates to product interchangeability and the differences between each of the individual LMWH preparations. Although differences between various commercially available products have been described in terms of molecular weight profile and biologic properties, very limited information on the direct comparison of individual products in a defined clinical setting is available at this time. European Pharmacopeia (EP) and the World Health Organization (WHO) have developed guidelines to characterize these agents in terms of molecular weight and biologic profiles. On a gravimetric basis, these potency assignments differ for anti-Xa and anti-IIa activities in terms of U potency per mg. The relative distribution of various molecular weight components has also been reported to vary. The oligosaccharide composition, microstructural differences in terms of specific sugars and the presence of unique structural features and the interaction with endogenous mediators such as antithrombin (AT) and heparin cofactor II (HC II) also differ. At equivalent anti-Xa levels, the amount of the anti-IIa activity and anticoagulant activity differs. Since the bioavailability and relative pharmacokinetics of the anti-Xa and anti-IIa effects are different, the specific pharmacodynamic effects of these drugs also differ. A large preclinical data base is now available on the differences between various LMWHs. However, only limited clinical data is available in the current literature. To date, the LMWHs have been primarily used for the management of post-surgical DVT. Only smaller dosages (30-40 mg or 2,500 to 4,000 anti-Xa U total dose) have been used. In these studies, because of the low dose and subcutaneous route of administration, the differences in clinical effects are rather small. Since LMWHs are now developed for therapeutic use, where relatively higher doses are used, these pharmacokinetic/pharmacodynamic differences will become more apparent. The reported differences in the clinical efficacy of LMWHs in such indications as unstable angina may be due to their pharmacologic properties and molecular composition. There are also major differences in the non-anticoagulant actions of these agents such as their ability to interact with growth factors and antithrombotic effects. Based on the available literature, it can be concluded that each product exhibits individuality.

Several of the newly developed anti-Xa and anti-IIa agents have been shown to influence the International Normalized Ratio (INR) values. During phase I trials with normal healthy volunteers and phase II study patients who were given warfarin and concomitant anti-IIa or anti-Xa agents, it has been reported that INR values were falsely elevated. It is of critical importance to know of the effects of these agents on INR to avoid dosage errors. To study the influence of these agents on INR, we used several anti-IIa agents (argatroban, recombinant hirudin, efegatran, and PEG-hirudin) and anti-Xa drugs (pentasaccharides such as fondaparinux and idraparinux, DX-9065a and JTV-803). The anti-IIa drugs were supplemented in citrated plasma at a concentration of 0 to 1 microg/mL level and anti-Xa drugs in the range of 0 to 25 microg/mL. The IC(50) values for each of these agents were calculated. Four different commercially available prothrombin time (PT) reagents were used to perform the PT assays and to calculate the relative INR values. Direct synthetic factor IIa and Xa inhibitors exhibited a concentration-dependent increase in the INR values. Hirudin, efegatran, and PEG-hirudin showed a weaker effect, whereas argatroban showed a much higher elevation of the INR values. Synthetic indirect anti-Xa agents such as the pentasaccharide did not show any effect on the INR values. Furthermore, prothrombin time reagents with high ISI values exhibited disproportionally higher INR values for both the direct anti-Xa and anti-IIa agents. Elevation of INR values has therapeutic implications when non-oral anticoagulant drugs are used in combination with drugs such as warfarin. Because of the false elevation of INR values with some of the non-oral anticoagulant drugs, patients who are on concomitant warfarin therapy should be carefully evaluated for their corresponding INR values for proper dosing. To avoid dosing errors it is best not to use the INR values in the therapeutic monitoring of anti-Xa and anti-IIa agents either in the monotherapeutic or polytherapeutic modalities. These data also warrant the development clinically relevant methods for the monitoring of the concomitant use of newly developed anti-Xa and anti-IIa drugs with oral anticoagulants.

The term “movement system” has been defined as “represent(ing) the collection of systems (cardiovascular, pulmonary, endocrine, integumentary, nervous, and musculoskeletal) that interact to move the body or its component parts.”5 Although we do not dispute the advantage of defining the “movement system” as a physiological system, we contend that how the profession is identified with a monolithic “movement system” is imprudent. We contend that our scientific expertise regarding “movement optimization” should move forward by reconsidering how movement is produced (and potentially optimized) as a behavioral phenomenon in itself and abandon further attempts to promote “the movement system” with a purportedly unique and static label. We believe that reframing diagnosis is possible if there is a move away from an exclusive emphasis on classification of anatomical and physiological deviations from “normal” based on organismic constraints when such data yield, at best, an incomplete insight into functional performance that includes environmental and task constraints. The recent application of complex systems approaches to disciplines as diverse as medicine, biology, economics, and meteorology warrants thoughtful consideration of the potential benefits of incorporating similar advances in conceptualization of the central questions in physical therapy.

The aim of this pilot study was to investigate feasibility, tolerability, and effect of modified constraint‐induced movement therapy (mCIT) in children with hemiparesis after arterial ischaemic stroke (AIS). Children with chronic hemiparesis and impaired hand function after AIS had mCIT for 2 hours a day, 5 days a week for 4 weeks. Pre‐ and post‐therapy assessments included indices of sensorimotor function, quality of upper limb movement, functional therapy goals, and child and parent interviews. Of eight participants initially recruited, six (one male, five females) completed mCIT (median age 12y 3mo; range 6y 10mo–15y 2mo). Hemiparesis was predominantly spastic in three participants and dystonic in the others; all had severely impaired hand function. After mCIT there were no significant improvements in sensorimotor function or quality of upper limb movement. However, all children improved in individual therapy goals related to functional performance. Children and parents were positive about mCIT. The use of mCIT is a promising intervention for children with chronic acquired hemiparesis. In this severely impaired group functional improvements were seen after therapy despite unchanged sensorimotor measures.