For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.
An 8-month-old girl who seemed certain to die from the infantile form of hypophosphatasia, an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), underwent the first trial of bone marrow cell transplantation for this heritable type of rickets. After cytoreduction, she was given T-cell-depleted, haplo-identical marrow from her healthy sister. Chimerism in peripheral blood and bone marrow became 100% donor. Three months later, she was clinically improved, with considerable healing of rickets and generalized skeletal remineralization. However, 6 months post-transplantation, worsening skeletal disease recurred, with partial return of host hematopoiesis. At the age of 21 months, without additional chemotherapy or immunosuppressive treatment, she received a boost of donor marrow cells expanded ex vivo to enrich for stromal cells. Significant, prolonged clinical and radiographic improvement followed soon after. Nevertheless, biochemical features of hypophosphatasia have remained unchanged to date. Skeletal biopsy specimens were not performed. Now, at 6 years of age, she is intelligent and ambulatory but remains small. Among several hypotheses for our patient's survival and progress, the most plausible seems to be the
Summary:Delayed engraftment, graft failure, and adverse transplant-related events have been observed in unrelated umbilical cord blood (UCB) recipients, particularly in those receiving a low leukocyte cell dose and in CML patients. We report the outcomes of two older adult patients with high risk CML who received a low leukocyte cell dose of unmanipulated UCB cells supplemented with ex vivo expanded (AastromReplicell System) UCB cells. Each engrafted promptly and neither patient experienced GVHD or life-threatening infection. Both remain engrafted with cells exclusively of donor origin and are in cytogenetic remission at 19 and 8 months follow-up. Ex vivo expanded UCB cells appear to facilitate hematopoietic recovery and therefore may increase the number of CML patients eligible for unrelated UCB transplant. Bone Marrow Transplantation (2000) 25, 797-799. Keywords: chronic myelogenous leukemia; umbilical cord blood transplant; ex vivo expansion Transplantation of umbilical cord blood (UCB) from related and unrelated donors has been performed in an attempt to increase the number of potential allogeneic stem cell donors. 1,2 The limited availability of unrelated donor UCB units of adequate nucleated cell dose, however, restricts its application in older adult patients. Ex vivo expansion of UCB in small and clinical-scale regulated perfusion experiments (AastromReplicell System, Ann Arbor, MI, USA) has been proven capable of significantly increasing the number of total nucleated cells, CFU-GM, and longterm culture initiating cells. 3 Therefore, the effect of supplementing unrelated donor UCB with ex vivo expanded UCB cells from the same donor was evaluated in two older adult patients with high risk CML and no alternative donor.
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