183 research outputs found
To Treat or Not To Treat—From Guidelines to Individualized Patient Management
Immune thrombocytopenia (ITP) is a rare disorder. Evidence-based guidelines provide
important information for hematologists, as well as diagnostic and therapeutic recommendations
to other physicians with limited expertise in the field. However, guidelines in pediatric
and adult ITP do not answer some imperative questions: which patient is at risk of severe
bleeding and requires pharmacologic treatment? Who will recover spontaneously? Is splenectomy
still an appropriate second-line treatment for all chronic or persistent ITP patients? This
review summarizes the current approach to these important issues, the patients’ perspective,
and how we can improve individual patient managemen
Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion
ObjectiveThe risk for thrombosis is increased after the Fontan operation. It is unknown whether children with univentricular heart disease have an intrinsic coagulation anomaly or acquire a defect in coagulation during the course of the staged repair. This prospective, longitudinal study evaluated changes in coagulation profiles in a cohort of patients with hypoplastic left heart syndrome from stage I palliation through completion of the Fontan operation.MethodsThirty-seven patients with hypoplastic left heart syndrome were enrolled prospectively, and the concentration of factors II, V, VII, VIII, IX, X, proteins C and S, fibrinogen, antithrombin, serum albumin, and liver enzymes were measured before stage I palliation (mean age 4 ± 2 days), before bidirectional Glenn (mean age 5.9 ± 1.8 months), before the Fontan procedure (mean age 27.1 ± 6.6 months), and after the Fontan procedure (mean age 49 ± 17.6months). Healthy children were used as age-matched controls for coagulation factors. Demographic, hemodynamic variables, and elapsed time after the Fontan procedure were evaluated as possible predictors of coagulation abnormalities.ResultsSignificantly lower levels of both procoagulation and anticoagulation factors were demonstrated through to completion of the Fontan procedure. After the Fontan procedure, there was a significantly higher factor VIII level (P < .005) but no correlation with hemodynamic variables or liver function.ConclusionThis longitudinal study in patients with identical cardiac disease and staged surgical procedures confirms the increase in factor VIII level after the Fontan procedure. This is an acquired defect, and although the cause remains to be determined, monitoring factor VIII levels after the Fontan operation could indicate a subset of patients at risk for thrombosis
Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion
ObjectiveThe risk for thrombosis is increased after the Fontan operation. It is unknown whether children with univentricular heart disease have an intrinsic coagulation anomaly or acquire a defect in coagulation during the course of the staged repair. This prospective, longitudinal study evaluated changes in coagulation profiles in a cohort of patients with hypoplastic left heart syndrome from stage I palliation through completion of the Fontan operation.MethodsThirty-seven patients with hypoplastic left heart syndrome were enrolled prospectively, and the concentration of factors II, V, VII, VIII, IX, X, proteins C and S, fibrinogen, antithrombin, serum albumin, and liver enzymes were measured before stage I palliation (mean age 4 ± 2 days), before bidirectional Glenn (mean age 5.9 ± 1.8 months), before the Fontan procedure (mean age 27.1 ± 6.6 months), and after the Fontan procedure (mean age 49 ± 17.6months). Healthy children were used as age-matched controls for coagulation factors. Demographic, hemodynamic variables, and elapsed time after the Fontan procedure were evaluated as possible predictors of coagulation abnormalities.ResultsSignificantly lower levels of both procoagulation and anticoagulation factors were demonstrated through to completion of the Fontan procedure. After the Fontan procedure, there was a significantly higher factor VIII level (P < .005) but no correlation with hemodynamic variables or liver function.ConclusionThis longitudinal study in patients with identical cardiac disease and staged surgical procedures confirms the increase in factor VIII level after the Fontan procedure. This is an acquired defect, and although the cause remains to be determined, monitoring factor VIII levels after the Fontan operation could indicate a subset of patients at risk for thrombosis
Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.
Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians
Review of chiral perturbation theory
A review of chiral perturbation theory and that of recent developments on the
comparison of its predictions with experiment is presented. Some interesting
topics with scope for further elaboration are touched upon.Comment: 7 pages in revtex, Invited talk at the workshop, QCD2002, Indian
Institute of Technology, Kanpur, November 18-22, 2002, to appear in the
proceeding
Cold Nuclear Matter Effects on Dijet Productions in Relativistic Heavy-ion Reactions at LHC
We investigate the cold nuclear matter(CNM) effects on dijet productions in
high-energy nuclear collisions at LHC with the next-to-leading order
perturbative QCD. The nuclear modifications for dijet angular distributions,
dijet invariant mass spectra, dijet transverse momentum spectra and dijet
momentum imbalance due to CNM effects are calculated by incorporating EPS, EKS,
HKN and DS param-etrization sets of parton distributions in nucleus . It is
found that dijet angular distributions and dijet momentum imbalance are
insensitive to the initial-state CNM effects and thus provide optimal tools to
study the final-state hot QGP effects such as jet quenching. On the other hand,
the invariant mass spectra and the transverse momentum spectra of dijet are
generally enhanced in a wide region of the invariant mass or transverse
momentum due to CNM effects with a feature opposite to the expected suppression
because of the final-state parton energy loss effect in the QGP. The difference
of EPS, EKS, HKN and DS parametrization sets of nuclear parton distribution
functions is appreciable for dijet invariant mass spectra and transverse
momentum spectra at p+Pb collisions, and becomes more pronounced for those at
Pb+Pb reactions.Comment: 10 pages, 11 figure
The CCAAT displacement protein/cut homeodomain protein represses osteocalcin gene transcription and forms complexes with the retinoblastoma protein-related protein p107 and cyclin A
Developmental control of bone tissue-specific genes requires positive and negative regulatory factors to accommodate physiological requirements for the expression or suppression of the encoded proteins. Osteocalcin (OC) gene transcription is restricted to the late stages of osteoblast differentiation. OC gene expression is suppressed in nonosseous cells and osteoprogenitor cells and during the early proliferative stages of bone cell differentiation. The rat OC promoter contains a homeodomain recognition motif within a highly conserved multipartite promoter element (OC box I) that contributes to tissue-specific transcription. In this study, we demonstrate that the CCAAT displacement protein (CDP), a transcription factor related to the cut homeodomain protein in Drosophila melanogaster, may regulate bone-specific gene transcription in immature proliferating osteoblasts. Using gel shift competition assays and DNase I footprinting, we show that CDP/cut recognizes two promoter elements (TATA and OC box I) of the bone-related rat OC gene. Overexpression of CDP/cut in ROS 17/2.8 osteosarcoma cells results in repression of OC promoter activity; this repression is abrogated by mutating OC box I. Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors. Our findings suggest that CDP/cut may represent an important component of a cell signaling mechanism that provides cross-talk between developmental and cell cycle-related transcriptional regulators to suppress bone tissue-specific genes during proliferative stages of osteoblast differentiation
Ringed sideroblasts in βâ thalassemia
Symptomatic βâ thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses are typically sufficient to diagnose the disease, sometimes the diagnosis can be more challenging. We describe a series of patients with βâ thalassemia whose diagnosis was delayed, required bone marrow examination in one affected member of each family, and revealed ringed sideroblasts, highlighting the association of this morphological finding with these disorders. Thus, in the absence of characteristic congenital sideroblastic mutations or causes of acquired sideroblastic anemia, the presence of ringed sideroblasts should raise the suspicion of βâ thalassemia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136352/1/pbc26324.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136352/2/pbc26324_am.pd
An effective theory for jet propagation in dense QCD matter: jet broadening and medium-induced bremsstrahlung
Two effects, jet broadening and gluon bremsstrahlung induced by the
propagation of a highly energetic quark in dense QCD matter, are reconsidered
from effective theory point of view. We modify the standard Soft Collinear
Effective Theory (SCET) Lagrangian to include Glauber modes, which are needed
to implement the interactions between the medium and the collinear fields. We
derive the Feynman rules for this Lagrangian and show that it is invariant
under soft and collinear gauge transformations. We find that the newly
constructed theory SCET recovers exactly the general result for the
transverse momentum broadening of jets. In the limit where the radiated gluons
are significantly less energetic than the parent quark, we obtain a jet
energy-loss kernel identical to the one discussed in the reaction operator
approach to parton propagation in matter. In the framework of SCET we
present results for the fully-differential bremsstrahlung spectrum for both the
incoherent and the Landau-Pomeranchunk-Migdal suppressed regimes beyond the
soft-gluon approximation. Gauge invariance of the physics results is
demonstrated explicitly by performing the calculations in both the light-cone
and covariant gauges. We also show how the process-dependent
medium-induced radiative corrections factorize from the jet production cross
section on the example of the quark jets considered here.Comment: 52 pages, 15 pdf figures, as published in JHE
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