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Biomedical subjects

W Hwang

Publications and source records attributed to W Hwang.

At least 19 recordsLinked to original sources
PubMed2006

Successful treatment of primary granulocytic sarcoma by non-myeloablative stem cell transplant.

Pre-leukemic granulocytic sarcoma (GS) may pose an initial diagnostic problem and its therapeutic approach has never been formally established. To our knowledge, non-myeloablative stem cell transplantation has been reported in cases of leukemic GS, but not in primary GS. We report a case of primary GS with extensive and aggressive presenting features and successfully treated with intensive chemotherapy followed by non-myeloablative allogeneic stem cell transplant. This resulted in complete remission with minimal complications. Our case demonstrates the potential of graft-vs.-tumour effect in the treatment of GS and suggests that non-myeloablative allogeneic stem cell transplant may be a feasible therapeutic approach for primary GS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Force transmission, compliance, and viscoelasticity are altered in the alpha7-integrin-null mouse diaphragm.

Alpha7beta1 integrin is a transmembrane structural and receptor protein of skeletal muscles, and the absence of alpha7-integrin causes muscular dystrophy. We hypothesized that the absence of alpha7-integrin alters compliance and viscoelasticity and disrupts the mechanical coupling between passive transverse and axial contractile elements in the diaphragm. In vivo the diaphragm is loaded with pressure, and therefore axial and transverse length-tension relationships are important in assessing its function. We determined diaphragm passive length-tension relationships and the viscoelastic properties of its muscle in 1-month-old alpha7-integrin-null mice and age-matched controls. Furthermore, we measured the isometric contractile properties of the diaphragm from mutant and normal mice in the absence and presence of passive force applied in the transverse direction to fibers in 1-month-old and 5-month-old mutant mice. We found that compared with controls, the diaphragm direction of alpha7-integrin-null mutants showed 1) a significant decrease in muscle extensibility in 1-year-old mice, whereas muscle extensibility increased in the 1-month-old mice; 2) altered muscle viscoelasticity in the transverse direction of the muscle fibers of 1-month-old mice; 3) a significant increase in force-generating capacity in the diaphragms of 1-month-old mice, whereas in 5-month-old mice muscle contractility was depressed; and 4) significant reductions in mechanical coupling between longitudinal and transverse properties of the muscle fibers of 1-month-old mice. These findings suggest that alpha7-integrin serves an important mechanical function in the diaphragm by contributing to passive compliance, viscoelasticity, and modulation of its muscle contractile properties.

Age Factors↗
PubMed2005

Therapeutic leukapheresis in hyperleukocytic leukaemias--the experience of a tertiary institution in Singapore.

INTRODUCTION: Hyperleukocytic leukaemias are associated with early mortality due to respiratory or neurological complications. They result from endothelial damage secondary to leukostasis. Leukapheresis, which aims to lower the white blood cell (WBC) count, has been used in certain patients to reduce the threat from leukostasis. However, there are very few published clinical investigations on the most appropriate use of leukapheresis in hyperleukocytosis. MATERIALS AND METHODS: We performed a retrospective analysis of 14 patients with hyperleukocytic leukaemia who presented to our institution and underwent therapeutic leukapheresis. We compare their clinical and biological characteristics and investigate the impact of leukapheresis on early mortality and long-term prognosis. RESULTS: The median presenting WBC count was 439 x 10(3)/mm(3). Although patients with acute myeloid leukaemia (AML) had the lowest median presenting WBC counts, they constituted the largest group of patients with symptomatic hyperleukocytosis. Leukapheresis was highly effective, with the mean absolute and percentage reduction in WBC after each cycle being 126 x 10(3)/mm(3) and 31.9% respectively. Four patients with AML died within 2 weeks of presentation despite prompt and effective leukapheresis. CONCLUSION: The interaction between the leukaemic cells and the vascular environment, a mechanism that none of the current therapies directly address, is probably more important in causing leukostasis than the absolute cell count itself.

Adolescent↗
PubMed2004

Successful treatment of idiopathic hypereosinophilic syndrome with imatinib mesylate: a case report.

Patients with idiopathic hypereosinophilic syndrome (HES) show persistent hypereosinophilia of unknown etiology that is associated with end-organ damage. Different treatments, including the use of corticosteroids and cytotoxics, have been investigated for HES with modest success. We describe a patient with HES who had significant end-organ damage from hypereosinophilia and remained refractory to conventional therapy. Therapy with imatinib mesylate, a selective tyrosine kinase inhibitor that is highly effective in treating patients with BCR-ABL-positive chronic myeloid leukemia, was tried with the patient. The result was impressive, with hematologic remission achieved after 12 days of administration. Our finding concurs with recent reports that imatinib mesylate may be a promising agent in the treatment of some cases of HES.

Adult↗
PubMed2004

In vitro biological characteristics of human cord blood-derived megakaryocytes.

INTRODUCTION: Umbilical cord blood (CB) has been used as an alternative source for haematopoietic stem cell transplantation (HSCT) in recent years. However, delayed platelet recovery is frequently associated with CB HSCT. Megakaryocytes (Mk) are the specialised precursors of platelets and they are among the rarest haemopoietic cell types. Despite the rapid expansion of our knowledge of megakaryopoiesis in recent years, many questions, such as the molecular regulatory mechanisms in Mk differentiation and maturation, platelet formation and release, remain unanswered in CB-derived megakaryopoiesis. Variations can be seen from the literature by individual investigators using different approaches for Mk-specific differentiation and maturation induction. The development of in vitro culture methods to obtain sufficient numbers of Mks from readily available haematopoietic stem cells is of value for both basic research and clinical applications. MATERIALS AND METHODS: The CD34+ cells from cord blood samples were cultured in serum-free medium with haematopoietic growth factors (GFs), such as IL-3, stem cell factor (SCF), and thrombopoietin (Tpo). The differentiation of Mk was monitored using Mk- and platelet-specific monoclonal antibodies and flow cytometric analysis. The morphology of the cultured cells was studied by both light and electronic microscopy (LM and EM). The involvement of the human Notch gene family members was studied by real time-polymerase chain reaction (RT-PCR). Maturation of the cultured Mks was studied using flow cytometric analysis for both platelet-specific surface markers and enodomitosis. Platelet activation was assessed in the cytoplasmic fragments harvested from the cultures. RESULTS: Specific Mk differentiation of >70% resulted from a 2-step culture approach using IL-3, SCF and Tpo for 7 days followed by Tpo only for another 14 days. RT-PCR showed high-level expression of both Notch-1 and its ligand, Jagged-1, in the cultured Mks. Limited levels of polyploidy (>4N, endomitosis, EnM) were observed in the cultured Mks. The results also showed that the cytoplasmic fragments from the cultures responded to platelet activation reagents, including ADP and collagen, marked by upregulation of platelet-specific activation markers, such as CD62P (P-selectin) and PAC-1 (gpalphaIIbbeta3). CONCLUSION: The methods used in this study are specific for differentiation of Mk from CB CD34+ cell, which can partially mature and produce functional platelets in vitro. This approach for human Mk differentiation could be further optimised and may be adapted on larger scales for clinical purposes.

Antibodies, Monoclonal↗
PubMed2002

Fitness versus longevity in age-structured population dynamics.

We examine the dynamics of an age-structured population model in which the life expectancy of an offspring may be mutated with respect to that of the parent. While the total population of the system always reaches a steady state, the fitness and age characteristics exhibit counter-intuitive behavior as a function of the mutational bias. By analytical and numerical study of the underlying rate equations, we show that if deleterious mutations are favored, the average fitness of the population reaches a steady state, while the average population age is a decreasing function of the average fitness. When advantageous mutations are favored, the average population fitness grows linearly with time t, while the average age is independent of the average fitness. For no mutational bias, the average fitness grows as t2/3.

Life Expectancy↗
PubMed2001

Dissolution in a field.

We study the dissolution of a solid by continuous injection of reactive "acid" particles at a single point, with the reactive particles undergoing biased diffusion in the dissolved region. When acid encounters the substrate material, both an acid particle and a unit of the material disappear. We find that the lengths of the dissolved cavity parallel and perpendicular to the bias grow as t(2/(d+1)) and t(1/(d+1)), respectively, in d dimensions, while the number of reactive particles within the cavity grows as t(2/(d+1)). We also obtain the exact density profile of the reactive particles and the relation between this profile and the motion of the dissolution boundary. The extension to variable acid strength is also discussed.

Journal Article↗
PubMed2001

Relation between pediatric experience and treatment recommendations for children and adolescents with kidney failure.

CONTEXT: Children and adolescent patients with renal failure are frequently cared for by adult subspecialists. While peritoneal dialysis is used in less than 17% of adults with kidney failure, it is the preferred dialysis treatment for children. National data show that 45% of children receiving dialysis are treated with peritoneal dialysis and pediatric nephrologists report its use in 65% of patients receiving dialysis. Whether differences in peritoneal dialysis use among children are due to the pediatric experience of the clinician has not been examined. OBJECTIVE: To assess whether the pediatric experience of nephrologists directly affects treatment recommendations for children with kidney failure. DESIGN: Cross-sectional survey using 10 case vignettes per survey based on random combinations of 8 patient characteristics (age, sex, race, distance from facility, cause of renal failure, family structure, education, and compliance). SETTING AND PARTICIPANTS: National random sample of office-, hospital-, and academic medical center-based adult and pediatric nephrologists, stratified by geographic region and conducted June to November 1999. Of 519 eligible physicians, 316 (61%) responded, including 191 adult and 125 pediatric nephrologists. MAIN OUTCOME MEASURE: Treatment recommendations for peritoneal dialysis vs hemodialysis, compared based on nephrologists' pediatric experience. RESULTS: After controlling for patient characteristics, pediatric nephrologists were 60% more likely than adult nephrologists to recommend peritoneal dialysis for identical patients (odds ratio, 1.61; 95% confidence interval, 1.35-1.92). This was true regardless of dialysis training, years in practice, practice setting, geography, or patient characteristics. CONCLUSIONS: Our data indicate that pediatric specialization of clinicians influences treatment recommendations for children and adolescents with end-stage renal disease. Referring children to adult subspecialists may lead to differences in treatment choices and processes of care.

Adolescent↗
PubMed2001

U.S. nephrologists' attitudes towards renal transplantation: results from a national survey.

BACKGROUND: Renal transplantation is the optimal treatment for persons with end-stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process.

Adult↗
PubMed2001

Infiltration through porous media.

We study the kinetics of infiltration in which contaminant particles, which are suspended in a flowing carrier fluid, penetrate a porous medium. The progress of the "invader" particles is impeded by their trapping on active "defender" sites which are on the surfaces of the medium. As the defenders are used up, the invader penetrates further and ultimately breaks through. We study this process in the regime where the particles are much smaller than the pores so that the permeability change due to trapping is negligible. We develop a family of microscopic models of increasing realism to determine the propagation velocity of the invasion front, as well as the shapes of the invader and defender profiles. The predictions of our model agree qualitatively with experimental results on breakthrough times and the time dependence of the invader concentration at the output. Our results also provide practical guidelines for improving the design of deep bed filters in which infiltration is the primary separation mechanism.

Journal Article↗
PubMed2001

Does growth retardation indicate suboptimal clinical care in children with chronic renal disease and those undergoing dialysis?

Growth failure is an important problem for children with end-stage renal disease (ESRD). Patients receiving replacement therapy for longstanding renal failure since childhood are likely to report dissatisfaction with certain aspects of their lives, especially with final adult height. Additionally, recent data suggest that growth failure in children with ESRD is associated with adverse clinical outcomes, including more frequent hospitalizations, and increased mortality. Although poor growth is unlikely to be the cause of this increased morbidity, growth failure may be a marker for a group of patients at high risk of adverse events. In this review, the authors describe the prevalence of growth retardation in children in the US with chronic renal disease, and present recent data on morbidity associated with growth failure. After reviewing published reports documenting available strategies to optimize growth, the authors conclude that despite vigilance and aggressive clinical management, a subset of children with long-term renal insufficiency and ESRD may still have poor linear growth. A discussion of "optimal care" leads one to consider evidence of current variability in the management of growth retardation in ESRD, and the strengths and limitations of developing practice guidelines to optimize growth in this population.

Child↗
PubMed2001

Desmin integrates the three-dimensional mechanical properties of muscles.

Striated muscle is a linear motor whose properties have been defined in terms of uniaxial structures. The question addressed here is what contribution is made to the properties of this motor by extramyofilament cytoskeletal structures that are not aligned in parallel with the myofilaments. This question arose from observations that transverse loads increase muscle force production in diaphragm but not in the hindlimb muscle, thereby indicating the presence of structures that couple longitudinal and transverse properties of diaphragmatic muscle. Furthermore, we find that the diaphragms of null mutants for the cytoskeletal protein desmin show 1) significant reductions in coupling between the longitudinal and transverse properties, indicating for the first time a role for a specific protein in integrating the three-dimensional mechanical properties of muscle, 2) significant reductions in the stiffness and viscoelasticity of muscle, and 3) significant increases in tetanic force production. Thus desmin serves a complex mechanical function in diaphragm muscle by contributing both to passive stiffness and viscoelasticity and to modulation of active force production in a three-dimensional structural network. Our finding changes the paradigm of force transmission among cells by placing our understanding of the function of the cytoskeleton in the context of the structural and mechanical complexity of muscles.

Animals↗
PubMed2000

Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A) receptor agonist.

BACKGROUND: We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A(2A) agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. METHODS AND RESULTS: A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to <20%. Adenosine and CGS-21680 were then separately infused to maximize left circumflex coronary artery (LCx) flow velocity. (201)Tl (0.5 mCi) and (99m)Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion (P<0.005). The decrease in systolic blood pressure was more prominent with adenosine than with CGS-21680 (P<0.005). In the control LCx zone, maximal myocardial blood flow (MBF) (measured by radioactive microspheres) increased 3.1-fold during adenosine infusion (P<0.005) and 3.8-fold during CGS-21680 infusion (P<0.005). In the stenotic LAD zone, MBF did not change significantly. During adenosine and CGS-21680 infusion, stenosis/control zone MBF ratios were comparable (0.32+/-0.11 versus 0.27+/-0.10, P=NS), and transmural (201)Tl and (99m)Tc-sestamibi count-activity ratios (0.48+/-0.11 and 0.51+/-0.09, respectively) were also comparable (P=NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. CONCLUSIONS: CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of (201)Tl and (99m)Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

Adenosine↗
PubMed2000

US nephrologists' recommendation of dialysis modality: results of a national survey.

Selection of a dialysis modality for persons with end-stage renal disease (ESRD) has important lifestyle and occupational implications. The factors affecting modality choice remain unclear, resulting in a low rate of peritoneal dialysis (PD) in the United States compared with other countries. A national survey of 271 US nephrologists was conducted from June 1997 to June 1998 to assess the relative importance of nonclinical and clinical factors related to dialysis modality selection for patients with ESRD. Hypothetical patient scenarios were randomly assigned to nephrologists to determine their recommendation for dialytic therapy based on patient demographic, clinical, and social factors. US nephrologists were more likely to recommend PD for men with ESRD compared with women (39% versus 33%; P: < 0.05; adjusted odds ratio, 1.44; 95% confidence interval, 1.15 to 1.80), as well as for patients with good compliance (adjusted odds ratio, 11.80; 95% confidence interval, 9.29 to 15.01), weight less than 200 lb (adjusted odds ratio, 2.3; 95% confidence interval, 1.8 to 2.9), residual renal function (adjusted odds ratio, 2.14; 95% confidence interval, 1.71 to 2.70), absence of diabetes (adjusted odds ratio, 2.0; 95% confidence interval, 1.6 to 2.5), and living with family (adjusted odds ratio, 1.7; 95% confidence interval, 1.4 to 2.1). Nephrologists in practice for 11 or more years were less likely to recommend PD. The association of male sex with PD therapy suggests a potential bias or sensitivity to women's perception of body image. Race was not associated with PD recommendations after controlling for other demographic and clinical characteristics. Because the incident US ESRD population is increasingly characterized by factors associated with not selecting PD (diabetes, obesity, malnourishment, living alone, and substance abuse problems), our results suggest that PD use may decrease over time.

Adult↗
PubMed2000

Purification and embryotropic roles of tissue inhibitor of metalloproteinase-1 in development of "HanWoo" (Bos taurus coreanae) oocytes co-cultured with bovine oviduct epithelial cells.

This study was conducted to purify a tissue inhibitor of metalloproteinase (TIMP)-1 in a serum-free medium conditioned with bovine oviduct epithelial cells (BOEC) and to evaluate its effect on development of "HanWoo" (Bos taurus coreanae) embryos to the blastocyst stage. In the first study using SDS-PAGE electrophoresis, the presence of 32 kDa proteins, which contains TIMP-1, was detected in the medium conditioned with BOEC, and TIMP-1 was then purified from the medium by gel filtration and HPLC techniques. When examined TIMP-1 secretion, fluorescent foci indicating the secretion of TIMP-1 were found after stained BOEC with fluorescein isothiocyanate. In the next experiment, two-cell embryos derived from in vitro-fertilization were cultured in a serum-free medium, to which 0, 1.25, 2.5 or 5 microg/ml of purified TIMP-1 was supplemented. More (P<0.05) embryos developed to the morula and blastocyst stages after the addition of 2.5 microg/ml to culture medium than after no addition. In conclusion, our data indicate that BOEC secrete TIMP-1 and this glycoprotein promotes the prehatched development of "HanWoo" embryos derived from in vitro-fertilization.

Animals↗
PubMed2000

Racial differences in access to the kidney transplant waiting list for children and adolescents with end-stage renal disease.

CONTEXT: Renal transplantation is the treatment of choice for pediatric patients with end-stage renal disease (ESRD). Black patients wait longer for kidney transplants than do white patients. OBJECTIVE: To determine whether the increased time to transplantation for black pediatric patients is attributable not only to a shortage of suitable donor organs, but also to racial differences in the time from a child's first treatment for ESRD until activation on the cadaveric kidney transplant waitlist. DESIGN: National longitudinal cohort study. SETTING: US Medicare-eligible, pediatric ESRD population. PATIENTS: Children and adolescents </=19 years old at the time of their first dialysis for ESRD between 1988 and 1993, followed through 1996. Patients who received living donor renal transplants were excluded from study. MAIN OUTCOME MEASURES: Time from first dialysis for ESRD until activation on the kidney transplant waiting list, relative hazard of activation on the waiting list for black compared with white pediatric patients. RESULTS: Comparisons of the time from first dialysis for ESRD to waitlisting among the 2162 white (60.7%) and 1122 black (31.5%) patients studied using survival analysis revealed that blacks were less likely to be waitlisted at any given time in follow-up. In multivariate analysis, even after controlling for patient age, gender, socioeconomic status, geographic region, incident year of renal failure, and cause of ESRD, blacks were 12% less likely to be waitlisted than were whites at any point in time (relative hazard:. 88: 95% confidence interval:.79-.97). CONCLUSIONS: Racial disparities in access to the renal transplant waiting list exist in pediatrics. Whether these disparities are attributable to differences in time of presentation to a nephrologist, physician bias in identification of transplant candidates, or patient preferences warrants further study.

Adolescent↗
PubMed1999

Dynamic behavior of driven interfaces in models with two absorbing states.

We study the dynamics of an interface (active domain) between different absorbing regions in models with two absorbing states in one dimension: probabilistic cellular automata models and interacting monomer-dimer models. These models exhibit a continuous transition from an active phase into an absorbing phase, which belongs to the directed Ising (DI) universality class. In the active phase, the interface spreads ballistically into the absorbing regions and the interface width diverges linearly in time. Approaching the critical point, the spreading velocity of the interface vanishes algebraically with a DI critical exponent. Introducing a symmetry-breaking field h that prefers one absorbing state over the other drives the interface to move asymmetrically toward the unpreferred absorbing region. In Monte Carlo simulations, we find that the spreading velocity of this driven interface shows a discontinuous jump at criticality. We explain that this unusual behavior is due to a finite relaxation time in the absorbing phase. The crossover behavior from the symmetric case (DI class) to the asymmetric case (directed percolation class) is also studied. We find the scaling dimension of the symmetry-breaking field y(h)=1.21(5).

Journal Article↗