Wiley-Liss Inc. (wiley-liss + inc)

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Selected Abstracts


Dynamic changes in the direction of the theta rhythmic drive between supramammillary nucleus and the septohippocampal system

HIPPOCAMPUS, Issue 6 2006
Bernat Kocsis
Abstract Neurons in the supramammillary nucleus (SUM) of urethane-anesthetized rats fire rhythmically in synchrony with hippocampal theta rhythm. As these neurons project to the septum and hippocampus, it is generally assumed that their role is to mediate ascending activation, leading to the hippocampal theta rhythm. However, the connections between SUM and the septohippocampal system are reciprocal; there is strong evidence that theta remains in the hippocampus after SUM lesions and in the SUM after lesioning the medial septum. The present study examines the dynamics of coupling between rhythmic discharge in the SUM and hippocampal field potential oscillations, using the directionality information carried by the two signals. Using directed transfer function analysis, we demonstrate that during sensory-elicited theta rhythm and also during short episodes of theta acceleration of spontaneous oscillations, the spike train of a subpopulation of SUM neurons contains information predicting future variations in rhythmic field potentials in the hippocampus. In contrast, during slow spontaneous theta rhythm, it is the SUM spike signal that can be predicted from the preceding segment of the electrical signal recorded in the hippocampus. These findings indicate that, in the anesthetized rat, SUM neurons effectively drive theta oscillations in the hippocampus during epochs of sensory-elicited theta rhythm and short episodes of theta acceleration, whereas spontaneous slow theta in the SUM is controlled by descending input from the septohippocampal system. Thus, in certain states, rhythmically firing SUM neurons function to accelerate the septal theta oscillator, and in others, they are entrained by a superordinate oscillatory network. 2006 Wiley-Liss Inc. [source]


Gonadal hormone modulation of hippocampal neurogenesis in the adult

HIPPOCAMPUS, Issue 3 2006
Liisa A.M. Galea
Abstract Gonadal hormones modulate neurogenesis in the dentate gyrus (DG) of adult rodents in complex ways. Estradiol, the most potent estrogen, initially enhances and subsequently suppresses cell proliferation in the dentate gryus of adult female rodents. Much less is known about how estradiol modulates neurogenesis in the adult male rodent; however, recent evidence suggests that estradiol may have a moderate effect on cell proliferation but enhances cell survival in the DG of newly synthesized cells but only when estradiol is administered during a specific stage in the cell maturation cycle in the adult male rodent. Testosterone likely plays a role in adult neurogenesis, although there have been no direct studies to address this. However, pilot studies from our laboratory suggest that testosterone up-regulates cell survival but not cell proliferation in the DG of adult male rats. Progesterone appears to attenuate the estradiol-induced enhancement of cell proliferation. Neurosteroids such as allopregnalone decrease neurogenesis in adult rodents, while pregnancy and motherhood differentially regulate adult neurogenesis in the adult female rodent. Very few studies have investigated the effects of gonadal hormones on male rodents; however, studies have indicated that there is a gender difference in the response to hormone-regulated hippocampal neurogenesis in the adult. Clearly, more work needs to be done to elucidate the effects of gonadal hormones on neurogenesis in the DG of both male and female rodents. 2006 Wiley-Liss Inc. [source]


Extracellular glucose concentration alters functional activity of the intestinal oligopeptide transporter (PepT-1) in Caco-2 cells

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2003
Vanessa M. D'Souza
Abstract The objective of this study was to determine the effect of different cell culture media glucose concentrations on the functional activity of PepT-1 in Caco-2 cells. Uptake kinetics of Gly-Sar into Caco-2 cells that were maintained in iso-osmotic media containing 25 or 5.5 mM glucose were determined in the presence and absence of amino acid-selective chemical modifiers and dithiothreitol. Inhibition of Gly-Sar uptake into Caco-2 cells was measured in the presence of dipeptides and xenobiotics exhibiting various binding affinities for the PepT-1. The effect of extracellular glucose on PepT-1 gene expression was assessed using comparative RT-PCR. Long-term exposure of Caco-2 cells to 25 mM glucose reduced maximum transport capacity for Gly-Sar uptake without altering PepT-1 gene expression. In contrast, binding affinity of Gly-Sar and other dipeptides or xenobiotics was not significantly changed. Chemical modification of Lys and Tyr residues decreased Vmax, while Cys modification increased the maximum transport capacity of the carrier. Preincubation of Caco-2 cells with dithiothreitol restored PepT-1 activity in cells maintained at 25 mM glucose. In conclusion, cell culture media containing 25 mM glucose decreases maximum transport capacity of PepT-1 in Caco-2 cells without affecting substrate recognition, at least in part, mediated via an oxidative pathway. 2003 Wiley-Liss Inc. and the American Pharmaeceutical Association J Pharm Sci 92:594,603, 2003 [source]


A review of the terms agglomerate and aggregate with a recommendation for nomenclature used in powder and particle characterization

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002
Gary Nichols
Abstract The terms "agglomerate" and "aggregate" are widely used by powder technologists to describe assemblages of particles that are found in dry powders and powders in liquid suspensions. Each term has a specific meaning but, unfortunately, they are frequently interchanged at will and this has resulted in universal confusion. This confusion is perpetuated by conflicting definitions in national and international standards and this presents problems when describing powder properties or communicating results in reports and research papers. This paper reviews the current status of the definitions, with particular emphasis on their use in the pharmaceutical industry. It is proposed that just one term, agglomerate, should be used to describe an assemblage of particles in a powder and that the term aggregate should be confined to pre-nucleation structures. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2103,2109, 2002 [source]


Effect of interferons on P-glycoprotein-mediated rhodamine-123 efflux in cultured rat hepatocytes

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002
Yukiko Akazawa
Abstract The effect of interferon (IFN)-, and IFN-, on P-glycoprotein (P-gp)-mediated efflux of rhodamin-123(Rho-123), a typical substrate of P-gp, was studied in rat hepatocytes in primary culture. After treatment with IFN-,, IFN-,, or both for 3 days, steady-state levels of Rho-123, incorporated into the hepatocytes, were measured to evaluate the P-gp activity. Whereas IFN-, did not affect the intracellular level of Rho-123, IFN-, treatment caused a significant increase of the level, suggesting that IFN-, treatment suppresses the expression of P-gp or its activity. A combination of the two types of IFN exhibited a similar effect to that of IFN-, alone. The effect of IFN-, was still observed in the presence of H2O2, which enhances the expression and activity of P-gp. Immunoblot analysis using a monoclonal antibody C219 revealed, however, that P-gp expression was increased after treatment with IFN-,, but only slightly by IFN-, treatment. These results suggest that the enhanced Rho-123 uptake of rat primary hepatocytes induced by IFN-, does not result from reduced expression of P-gp but, rather, from impaired maturation or dysfunction of the efflux transporter. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2110,2115, 2002 [source]


Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002
Francesca Maestrelli
Abstract Complexes of several 1,3,4-thiadiazole-2-sulfonamide derivatives possessing strong carbonic anhydrase (CA) inhibitory properties with ,-cyclodextrin and hydroxypropyl-,-cyclodextrin were obtained and characterized. Although the investigated CA inhibitors possessed very powerful inhibitory properties against the two CA isozymes involved in aqueous humor production within the eye, i.e., CA II and CA IV, these compounds were topically ineffective as intraocular pressure (IOP) lowering agents in normotensive/hypertensive rabbits, due to their very low water solubility. On the contrary, the cyclodextrin,sulfonamide complexes proved to be effective and long-lasting IOP lowering agents in the two animal models of glaucoma mentioned above. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2211,2219, 2002 [source]


Stabilization of proteins by low molecular weight multi-ions

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002
Donald S. Maclean
Abstract A method is described to identify small molecule ligands that stabilize proteins. The procedure is based on the hypothesis that molecules of various sizes containing two to four charges should occasionally bind to unpaired charged sites on the surface of proteins and by crosslinking such residues stabilize the native state of the liganded protein. A simple turbidity assay is employed that detects inhibition of protein aggregation under selected sets of conditions. Eight test proteins were screened and in all cases specific ligands were identified that inhibited protein aggregation at millimolar to micromolar concentrations. Only small effects of these stabilizers on protein biological activities were found. In some, but not all cases, circular dichroism and fluorescence studies provided direct evidence of the binding of stabilizing ligands to the proteins suggesting multiple mechanisms of stabilization. This approach should be applicable to the development of excipients for the stabilization of pharmaceutical proteins and industrial enzymes as well as serve as starting points for second-generation inhibitors of increased affinity and specificity. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2220,2229, 2002 [source]


Quantitative structure/property relationship analysis of Caco-2 permeability using a genetic algorithm-based partial least squares method

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002
Fumiyoshi Yamashita
Abstract Caco-2 cell monolayers are widely used systems for predicting human intestinal absorption. This study was carried out to develop a quantitative structure,property relationship (QSPR) model of Caco-2 permeability using a novel genetic algorithm-based partial least squares (GA-PLS) method. The Caco-2 permeability data for 73 compounds were taken from the literature. Molconn-Z descriptors of these compounds were calculated as molecular descriptors, and the optimal subset of the descriptors was explored by GA-PLS analysis. A fitness function considering both goodness-of-fit to the training data and predictability of the testing data was adopted throughout the genetic algorithm-driven optimization procedure. The final PLS model consisting of 24 descriptors gave a correlation coefficient (r) of 0.886 for the entire dataset and a predictive correlation coefficient (rpred) of 0.825 that was evaluated by a leave-some-out cross-validation procedure. Thus, the GA-PLS analysis proved to be a reasonable QSPR modeling approach for predicting Caco-2 permeability. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2230,2239, 2002 [source]


Distribution, metabolism, and excretion of a novel surface-active agent, purified poloxamer 188, in rats, dogs, and humans

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2002
J. Michael Grindel
Abstract Purified poloxamer 188 (PP188) is a nonionic, block copolymer surfactant with hemorheologic, antithrombotic, and anti-adhesive properties. PP188 is being studied in phase III clinical trials in sickle cell disease and has been found to be well tolerated and has demonstrated benefit in ameliorating the effects of acute painful vasoocclusive crisis. The disposition of PP188 was studied in rats, dogs, and humans to establish a basis for understanding the safety parameters in support of clinical trials. PP188 was primarily distributed in extracellular water with little or no uptake by red blood cells, and had its highest concentrations in highly perfused tissues such as the kidney, liver, spleen, lymph nodes, and gastrointestinal tract. PP188 had no apparent effect on P450 isozymes in vitro. Metabolism was limited (<,5% of dose) with a higher molecular weight copolymer being the only other material detected in plasma or urine. Renal clearance was the controlling route of clearance for PP188 from the body. The 48-h intravenous infusion doses of PP188 were cleared in all species by approximately 1 week after the cessation of dose administration. PP188's disposition is a model for other nonionic block copolymers with similar physical and chemical properties. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1936,1947, 2002 [source]


Noncovalent dimerization of paclitaxel in solution: Evidence from electrospray ionization mass spectrometry

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2002
Sarah A. Lorenz
Abstract Paclitaxel, a unique antimitotic chemotherapy agent that inhibits cell division by binding to microtubules and prevents them from "depolymerizing," has received widespread interest because of its efficacy in fighting certain types of cancer, including breast and ovarian cancer. Paclitaxel undergoes aggregation at millimolar concentrations in both aqueous media and solvents of low polarity (mimicking hydrophobic environments). Its aggregation may have impact on its aqueous stability and its ability to stabilize microtubules. Here, we investigated the dimerization phenomenon of paclitaxel by electrospray ionization mass spectrometry (ESI-MS). Paclitaxel dimers were stable in solutions of acetonitrile/aqueous ammonium acetate (80/20) and aqueous sodium acetate/acetonitrile (92/8 or 95/5) at various pH values. Additional experiments using solution-phase hydrogen/deuterium exchange were employed to ascertain whether or not the observed dimers were formed in solution or as an artifact of the ESI process by ion,molecule reaction. The evidence supports formation of the dimer in solution, and the approach used can be extended to investigation of other types of drug,drug interactions. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2057,2066, 2002 [source]


Reversal of multidrug resistance-associated protein-mediated daunorubicin resistance by camptothecin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002
David Chauvier
Abstract The multidrug-resistance (MR) status of camptothecin (CPT) was investigated in colon adenocarcinoma HT29 cells, leukemia K562, and breast carcinoma MCF7 cells expressing P-glycoprotein (Pgp) and/or MR-associated protein (MRP1). The concentration that induced 50% growth inhibition (IC50) against CPT was 0.14 and 0.20 ,M in parental K562/WT and MCF7/WT cells, respectively. The drug resistant subline KH30 and MCF7/VP cells, which both overexpress MRP1, presented IC50 values of 0.63 and 3.10 ,M, respectively. The resulting resistance indexes were 3.80 and 12.50, respectively. However, in KH300 cells, a cell line that preferentially overexpresses Pgp, the IC50 of CPT was 0.08 ,M and thus did not exhibit resistance against CPT. In MCF7/DoX cells, preferentially overexpressing Pgp, but also a significant level of MRP1, the IC50 of CPT was 0.64 ,M and thus presented a resistance index of 3.26 against CPT. The cytotoxic effect of CPT was modulated in cells expressing MRP1 (MCF7/VP, HT29 cells) by the specific MRP1 modulators, probenecid and MK571. These results led us to consider CPT as a substrate for MRP1 and a potential modulator of MRP1 activity. To test this hypothesis, we examined the ability of nontoxic concentrations of CPT to sensitize MRP1-overexpressing cells to daunorubicin (DNR). In MCF7/VP and KH30 cells, nontoxic concentrations of CPT were able to enhance cytotoxicity of DNR and its nuclear accumulation. Sequential and simultaneous associations of CPT (100 nM) and DNR provided complete reversal of resistance, thus showing a synergistic effect in KH30 cells. However, simultaneous association (with 10 or 20 nM CPT) had an additive effect in MCF7/VP. These data suggest that CPT could be proposed as a candidate for the reversal of the MRP1 phenotype at clinically achievable concentrations. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1765,1775, 2002 [source]


Ultrasound-compacted indomethacin/polyvinylpyrrolidone systems: Effect of compaction process on particle morphology and dissolution behavior

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002
Adamo Fini
Abstract Indomethacin (IMC)/polyvinylpyrrolidone systems were prepared under different technological conditions, using co-evaporation, kneading, traditional, and ultrasound (US) compaction. The materials thus obtained were milled and sieved and the powders were analyzed by using scanning electron microscopy to evaluate the morphology of the final particles and the fractal dimension of the particle contour. In the case of US-treated particles, scanning electron micrographs suggest that IMC could have partially covered the excipient granule surface, which appears lustrous and smooth, whereas after co-evaporation, the particles display a stratified structure. The external color of the granules, the hot stage microscopy examination, and the absence of the melting peak of the drug in thermograms supports the idea that IMC converts into an amorphous form under US discharge. Each technological treatment performed on the binary mixtures increases the dissolution rate of the drug, with respect to the pure drug and the physical mixture, but to a lesser extent than US compaction. US compaction and co-evaporation produce comparable results in improving the release of the drug. Polyvinylpyrrolidone offers better results than ,-cyclodextrin in promoting the dissolution of IMC, when both systems are compacted under US. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1880,1890, 2002 [source]


Prediction of steady-state skin permeabilities of polar and nonpolar permeants across excised pig skin based on measurements of transient diffusion: Characterization of hydration effects on the skin porous pathway

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002
Hua Tang
Abstract The applicability of a two-parameter Fickian diffusion model for predicting the skin steady-state permeability based on measurements of the transient transport of permeants across the skin was tested. Using five model permeants possessing different physicochemical properties and pig skin as the model membrane, the skin permeabilities predicted by the two-parameter Fickian diffusion model were compared with the measured skin permeabilities. Results show that the transient skin permeation profiles of the hydrophobic permeants, estradiol, testosterone, and dolichol, across split-thickness pig skin can be modeled adequately by the two-parameter Fickian diffusion model (with constant parameter values), and therefore, that this model can be utilized to shorten the experimental time required to determine the skin permeabilities of these compounds. However, the skin permeabilities of the highly hydrophilic permeants, mannitol and sucrose, predicted by the two-parameter Fickian diffusion model (with constant parameter values) were significantly lower than the experimentally determined values, indicating that the dominant skin pathway of polar permeants within the excised pig skin undergoes significant structural changes during the in vitro diffusion cell studies. Although the skin permeability values determined experimentally using the traditional steady-state method normally correspond to a highly hydrated skin sample, the two-parameter Fickian diffusion model enables an estimation of the skin permeability of the skin membrane at its less-hydrated state (a condition more representative of in vivo and clinical situations). Using the two-parameter Fickian diffusion model and a recently developed skin porous-pathway theory, the effects of skin hydration on the skin porous pathway within the excised pig skin were characterized. Specifically, we found that hydration leads to induction of new pores/reduction of the tortuosity of existing pores within the excised pig skin during the 48 h diffusion cell studies conducted, while the skin average pore radii remain relatively constant (,26 ) for up to 48 h. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1891,1907, 2002 [source]


Shear-induced degradation of plasmid DNA

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
C. S. Lengsfeld
Abstract The majority of gene therapy clinical trials use plasmid DNA that is susceptible to shear-induced degradation. Many processing steps in the extraction, purification, and preparation of plasmid-based therapeutics can impart significant shear stress that can fracture the phosphodiester backbone of polynucleotides, and reduce biological activity. Much of the mechanistic work on shear degradation of DNA was conducted over 30 years ago, and we rely heavily on this early work in an attempt to explain the empirical observations of more recent investigations concerning the aerosolization of plasmids. Unfortunately, the sporadic reports of shear degradation in the literature use different experimental systems, making it difficult to quantitatively compare results and reach definitive mechanistic conclusions. In this review, we describe the forces imparted to DNA during shear stress, and use published data to quantitatively evaluate their relative effects. In addition, we discuss the effects of molecular weight, strain rate, particle size, flexibility, ionic strength, gas,liquid interfaces, and turbulence on the fluid flow degradation of supercoiled plasmid DNA. Finally, we speculate on computational methods that might allow degradation rates in different experimental systems to be predicted. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1581,1589, 2002 [source]


Factors affecting the deposition of inhaled porous drug particles

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
Cynthia J. Musante
Abstract Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.1, 1.0, and 2.0 g/cm3 were considered. Particle size distributions were defined with mass median aerodynamic diameters (MMADs) ranging from 1 to 3 ,m and geometric standard deviations ranging from 1.5 to 2.5, representing particles in the respirable size range. Breathing rates of 30 and 60 L/min with tidal volumes of 500 to 3000 mL were assumed, simulating shallow to deep breaths from a dry powder inhaler. Particles with a high density and a small geometric diameter had slightly greater deposition fractions than particles that were aerodynamically similar, but had lower density and larger geometric size (typical of manufactured porous particles). This can be explained by the fact that particles with a small geometric diameter deposit primarily by diffusion, which is a function of geometric size but is independent of density. As MMAD increased, the effect of density on deposition was less pronounced because of the decreased efficiency of diffusion for large particles. These data suggest that polydisperse aerosols containing a significant proportion of submicron particles will deposit in the pulmonary airways with greater efficiency than aerodynamically similar aerosols comprised of geometrically larger porous particles. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1590,1600, 2002 [source]


Measuring the surface area of aluminum hydroxide adjuvant

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
Cliff T. Johnston
Abstract The traditional method of determining surface area, nitrogen gas sorption, requires complete drying of the sample prior to analysis. This technique is not suitable for aluminum hydroxide adjuvant because it is composed of submicron, fibrous particles that agglomerate irreversibly upon complete removal of water. In this study, the surface area of a commercial aluminum hydroxide adjuvant was determined by a gravimetric/FTIR method that measures the water adsorption capacity. This technique does not require complete drying of the adjuvant. Five replicate determinations gave a mean surface area of 514 m2/g and a 95% confidence interval of 36 m2/g for a commercial aluminum hydroxide adjuvant. The X-ray diffraction pattern and the Scherrer equation were used to calculate the dimensions of the primary crystallites. The average calculated dimensions were 4.5,,2.2,,10 nm. Based on these dimensions, the mean calculated surface area of the commercial aluminum hydroxide adjuvant was 509 m2/g, and the 95% confidential interval was 30 m2/g. The close agreement between the two surface area values indicates that either method may be used to determine the surface area of aluminum hydroxide adjuvant. The high surface area, which was determined by two methods, is an important property of aluminum hydroxide adjuvants, and is the basis for the intrinsically high protein adsorption capacity. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1702,1706, 2002 [source]


Nasal administration of low molecular weight heparin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
John Arnold
Abstract The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the Cmax and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the Cmax and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0,,0.4% in the absence of TDM to 19,,0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1707,1714, 2002 [source]


Near-fatal uterine hemorrhage during induction chemotherapy for acute myeloid leukemia: A case report of bilateral uterine artery embolization

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2004
John T. Phelan II
Abstract Severe transfusion-dependent uterine hemorrhage is a relatively uncommon complication of induction chemotherapy for acute myeloid leukemia (AML). Even less common is the failure of systemic conjugated estrogens in this setting. We report a case of life-threatening uterine hemorrhage in a 38-year-old woman in the setting of transfusion-refractory thrombocytopenia after completing induction chemotherapy for AML. She experienced dramatic breakthrough uterine hemorrhage despite multiple platelet transfusions, conjugated estrogens, recombinant factor VIIa, ,-aminocaproic acid, and intracavitary thrombin-soaked gauze tamponade. At the point of near-exsanguination in the setting of hypotension, hematocrit of 14%, and a platelet count of 3,000/,L, she underwent bilateral uterine artery embolization which proved immediately successful. We review the literature and indications for this procedure in the oncologic patient care setting. Am. J. Hematol. 77:151,155, 2004. 2004 Wiley-Liss Inc. 2004 Wiley-Liss, Inc. [source]


Two factor XI mutations in a Chinese family with factor XI deficiency

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2003
W.Y. Au
Abstract We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713,T mutation resulting in Gln263,Term, and an exon-10 C979,A mutation resulting in Tyr351,Term. Two daughters were heterozygous for the Gln263,Term mutation and two for the Try351,Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263,Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351,Term mutation is novel. Am. J. Hematol. 74:136,138, 2003. 2003 Wiley-Liss Inc. [source]


Type I Glanzmann thrombasthenia: Most common subtypes in North Indians

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2003
M. Kannan
Abstract The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians. Glanzmann thrombasthenia was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to ADP, ADR, arachidonic acid, and collagen. Flow cytometry revealed variable GPIIb/IIIa expression by CD61 and CD41 in patients with Glanzmann thrombasthenia on the basis of CD61 levels, six patients were subtyped as type I because they had absent GPIIb/IIIa, three patients were subtyped as type II because their GPIIb/IIIa levels varied from 7.72% to 20.40%, and one patient was diagnosed as type III, because his clot retraction was 60% and GPIIb/IIIa was 46.0% of normal. Four fathers, three mothers, and five siblings were found to have GPIIb/IIIa levels less than 35% of normal. It is possible that low GPIIb/IIIa levels in family members may reflect their carrier status. It is postulated that flow cytometric estimation of GPIIb/IIIa in parents/siblings may detect carrier status in Glanzmann thrombasthenia. Am. J. Hematol. 74:139,141, 2003. 2003 Wiley-Liss Inc. [source]


Combined catheter ventricular septal defect closure and multivessel coronary stenting to treat postmyocardial infarction ventricular septal defect and triple-vessel coronary artery disease: A case report

CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 3 2004
Rajaram Anantharaman
Abstract Ventricular septal defect following acute myocardial infarction is a rare but life-threatening complication. Early surgical closure improves survival but carries a considerable risk. Percutaneous transcatheter closure is an alternative but experience to date is limited. We report a case of successful transcatheter closure of postmyocardial infarction ventricular septal defect (VSD) in a 55-year-old male with the Amplatzer muscular VSD occluder device and complete percutaneous revascularization with successful multivessel coronary stenting for three-vessel disease as a staged procedure. The technique and its potential use as an alternative to surgical approach for treatment of acute myocardial infarction and its complication (VSD) are discussed. Catheter Cardiovasc Interv 2004;63:311-313 2004 Wiley-Liss Inc. [source]