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Thomas D Coates

Publications and source records attributed to Thomas D Coates.

14 recordsLinked to original sources
PubMed2006

Spectral imaging microscopy web sites and data.

The Internet is enabling greater access to spectral imaging publications, spectral graphs, and data than that was available a generation ago. The spectral imaging systems discussed in this issue of Cytometry work because reagent and hardware spectra are reproducible, reusable, and provide input to spectral unmixing and spectral components recognition algorithms. These spectra need to be readily available in order to determine what to purchase, how to use it, and what the output means. We refer to several commercially sponsored and academic spectral web sites and discuss our spectral graphing and data sites. Sites include fluorescent dye graph servers from Invitrogen/Molecular Probes, BD Biosciences, Zeiss/Bio-Rad Cell Sciences, and filter set servers from Chroma Technology and Omega Optical. Several of these sites include data download capabilities. Recently, two microscope manufacturers have published on their web sites transmission curves for select objective lenses-crucial data for anyone doing multiphoton excitation microscopy. Notable among the academic sites, PhotoChemCAD 2.0 has over 200 dyes and a downloadable database/graphing program, and the USC-A Chemistry UV-vis Database displays absorption spectra of many dyes and indicators used in clinical histology and pathology. Our Fluorescent Spectra graphing/calculator site presents dyes, filters, and illumination data from many of these and additional sources. PubSpectra is our free download site which uses Microsoft Excel files as standardized human/machine readable format with over 2,000 biomedical spectra. The principle that data is not subject to copyright provides a framework in which all scientific data should be made freely accessible.

Algorithms↗
PubMed2006

Improved R2* measurements in myocardial iron overload.

PURPOSE: To optimize R2*(1/T2*) measurements for cardiac iron detection in sickle cell and thalassemia patients. MATERIALS AND METHODS: We studied 31 patients with transfusion-dependent sickle cell disease and 48 patients with thalassemia major; myocardial R2* was assessed in a single midpapillary slice using a gated gradient-echo pulse sequence. Pixel-wise maps were coregistered among the patients to determine systematic spatial fluctuations in R2*. The contributions of minimum TE, echo spacing, signal-decay model, and region-of-interest (ROI) choice were compared in synthetic and acquired images. RESULTS: Cardiac relaxivity demonstrated characteristic circumferential variations regardless of the degree of iron overload. Within the interventricular septum, a gradient in R2* from right to left ventricle was noted at high values. Pixel-wise and ROI techniques yielded nearly identical values. Signal decay was exponential but a constant offset or second exponential term was necessary to avoid underestimation at high iron concentration. Systematic underestimation of R2* was observed for higher minimum TE, limiting the range of iron concentrations that can be profiled. Fat-water oscillations, although detectable, represented only 1% of the total signal. CONCLUSION: Clinical cardiac R2* measurements should be restricted to the interventricular septum and should have a minimum TE < or = 2 msec. ROI analysis techniques are accurate; however, offset-correction is essential.

Anemia, Sickle Cell↗
PubMed2006

MRI detects myocardial iron in the human heart.

Iron-induced cardiac dysfunction is a leading cause of death in transfusion-dependent anemia. MRI relaxation rates R2(1/T2) and R2*(1/T2*) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R2* behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R2* were compared with iron distribution in one freshly deceased, unfixed, iron-loaded heart. R2 and R2* were proportionally related to regional iron concentrations and highly concordant with one another within the interventricular septum. A comparison of postmortem and in vitro measurements supports the notion that cardiac R2* should be assessed in the septum rather than the whole heart. These data, along with measurements from controls, provide bounds on MRI-iron calibration curves in human heart and further support the clinical use of cardiac MRI in iron-overload syndromes.

Adult↗
PubMed2005

Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy.

BACKGROUND: Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. METHODS AND RESULTS: Twelve gerbils underwent iron dextran loading (200 mg . kg(-1) . wk(-1)) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. CONCLUSIONS: MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans.

Animals↗
PubMed2005

MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients.

Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* (1/T2*) measured by magnetic resonance imaging (MRI) have different advantages for HIC estimation. This article compares noninvasive iron estimates using both optimized R2 and R2* methods in 102 patients with iron overload and 13 controls. In the iron-overloaded group, 22 patients had concurrent liver biopsy. R2 and R2* correlated closely with HIC (r2 > or = .95) for HICs between 1.33 and 32.9 mg/g, but R2 had a curvilinear relationship to HIC. Of importance, the R2 calibration curve was similar to the curve generated by other researchers, despite significant differences in technique and instrumentation. Combined R2 and R2* measurements did not yield more accurate results than either alone. Both R2 and R2* can accurately measure hepatic iron concentration throughout the clinically relevant range of HIC with appropriate MRI acquisition techniques.

Adolescent↗
PubMed2005

Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens.

MRI is becoming an increasingly important tool to assess iron overload disorders, but the complex nature of proton-iron interactions has troubled noninvasive iron quantification. Intersite and intersequence variability as well as methodological inaccuracies have been limiting factors to its widespread clinical use. It is important to understand the underlying proton relaxation mechanisms within the (human) tissue environment to address these differences. In this respect, NMR relaxometry was performed on 10 fresh human liver biopsy specimens taken from patients with transfusion-dependent anemia. T1 (1/R1) inversion recovery, T2 (1/R2) single echo, and multiecho T2 CPMG measurements were performed on a 60-MHz Bruker Minispectrometer. NMR parameters were compared to quantitative iron levels and tissue histology. Relaxivities R1 and R2 both increased linearly with hepatic iron content, with R2 being more sensitive to iron. CPMG data were well described by a chemical-exchange model and predicted effective iron center dimensions consistent with hemosiderin-filled lysosomes. Nonexponential relaxation was evident at short refocusing intervals with R2 and amplitude behavior suggestive of magnetic susceptibility-based compartmentalization rather than anatomic subdivisions. NMR relaxometry of human liver biopsy specimens yields unique insights into the mechanisms of tissue-iron relaxivity.

Algorithms↗
PubMed2005

Fetal haemoglobin augmentation in E/beta(0) thalassaemia: clinical and haematological outcome.

Patients with E/beta(0) thalassaemia, the most common haemoglobinopathy in many Asian countries, might benefit from drugs that increase fetal and total haemoglobin and thereby decrease the need for transfusions. The long-term clinical efficacy and safety of such therapy is unknown, limiting its use in countries where resources for safe and regular transfusion are scarce. In this study, 45 patients were treated with hydroxyurea (18-20 mg/kg) for 24+/-9 months, hydroxyurea with sodium phenyl butyrate (n=8) and hydroxyurea with erythropoietin (n=9), each for approximately 6 months, and followed for 3 years from study exit. Hydroxyurea had minimal toxicity, resulted in a mean 1.3 g/dl steady-state increase in haemoglobin in 40% of patients, and a milder response (<OR=1 g/dl) in the others. Baseline haemoglobin F was significantly associated with an increase in haemoglobin (P<0.001). Combined treatment with erythropoietin benefited selected patients, but the addition of sodium phenyl butyrate had no effect. Of the 27/45 patients who discontinued regular transfusions before the study, 13 remained transfusion independent during long-term follow-up, 6/13 continued hydroxyurea. Hydroxyurea moderately increased steady-state haemoglobin in a sub-group of E/beta(0) thalassaemia patients and can be considered for patients with intermediate severity disease, thus delaying or avoiding the need for life-long transfusions. Continuous monitoring of toxicity and growth is required.

Adolescent↗
PubMed2005

Single and combination drug therapy for fetal hemoglobin augmentation in hemoglobin E-beta 0-thalassemia: Considerations for treatment.

Patients with hemoglobin E (Hb E)-beta 0-thalassemia, one of the most common hemoglobinopathies worldwide, could benefit from drugs that increase fetal and total hemoglobin levels and thereby decrease the need for transfusions. The long-term clinical outcome of such therapy, its hematologic effects, and which patients are likely to benefit from treatment are unknown. Consequently, the use of such drugs for Hb E-beta 0-thalassemia is limited, and countries where resources for safe and regular transfusion are scarce cannot benefit from them. In a multicenter trial of 42 patients treated with hydroxyurea for two years, almost half the patients demonstrated a significant increase in steady-state hemoglobin level. Drug toxicity was minimal. Combined treatment of hydroxyurea with erythropoietin benefited selected patients, but the addition of sodium phenyl butyrate was ineffective. After 5 years of follow-up, a subset of patients remained off transfusions. Hydroxyurea should be considered for a subset of Hb E-beta 0-thalassemia patients.

Blood Transfusion↗
PubMed2005

Physiology and pathophysiology of iron cardiomyopathy in thalassemia.

Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as the use of MRI to monitor it. Despite regular transfusions, thalassemia major patients have larger ventricular volumes, higher cardiac outputs, and lower total vascular resistances than published data for healthy control subjects; these hemodynamic findings are consistent with chronic anemia. Cardiac iron overload increases the relative risk of further dilation, arrhythmias, and decreased systolic function. However, many patients are asymptomatic despite heavy cardiac burdens. We explore possible mechanisms behind cardiac iron-function relationships and relate these mechanisms to clinical observations.

Buffers↗
PubMed2003

Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease.

Cardiac T2* (magnetic resonance imaging relaxation parameter) is abnormally low in approximately 40% of adults with thalassemia major (TM), suggesting myocardial iron deposition, but it is unknown at what age this occurs. To address this question, we measured cardiac T2* and function in 19 young patients (aged 7-26 years) with TM as well as 17 patients receiving long-term transfusions for sickle cell anemia (SCA) matched for age, sex, and liver iron content. Cardiac T2* was normal in all of the SCA patients but was low (high iron) in 8 of 19 TM patients. Abnormal T2* was observed only in the TM patients receiving transfusions for 13 years or longer and was correlated with ferritin but not liver iron levels. Cardiac dysfunction was present in 3 of the 8 patients with low T2*. Cardiac T2* changes have a long latency relative to liver iron accumulation. Total transfusional burden is a significant independent risk factor for low cardiac T2* and may partially account for differences observed between patients with SCA and TM.

Adolescent↗
PubMed2003

Placenta growth factor activates monocytes and correlates with sickle cell disease severity.

Sickle cell disease (SCD) results in chronic hypoxia and secondarily increased erythropoietin concentrations. Leukocytosis and activated monocytes are also observed in SCD in absence of infection or vaso-occlusion (steady state), the reasons for which are unknown. We found that erythroid cells produced placenta growth factor (PlGF), an angiogenic growth factor belonging to the vascular endothelial growth factor (VEGF) family, and its expression was induced in bone marrow CD34+ progenitor cells in the presence of erythropoietin. Furthermore, the steady state circulating PlGF levels in subjects with severe SCD (at least 3 vaso-occlusive crises [VOCs] per year) were 18.5 +/- 1.2 pg/mL (n = 9) compared with 15.5 +/- 1.2 pg/mL (n = 13) in those with mild SCD (fewer than 3 VOCs per year) and 11.3 +/- 0.7 pg/mL (n = 9) in healthy controls (P <.05), suggesting a correlation between PlGF levels and SCD severity. In addition, PlGF significantly increased mRNA levels of the proinflammatory cytochemokines interleukin-1beta, interleukin-8, monocyte chemoattractant protein-1, and VEGF in peripheral blood mononuclear cells (MNCs) of healthy subjects (n = 4; P <.05). Expression of these same cytochemokines was significantly increased in MNCs from subjects with SCD at steady state (n = 14), compared with healthy controls. Of the leukocyte subfractions, PlGF stimulated monocyte chemotaxis (P <.05, n = 3). Taken together, these data show for the first time that erythroid cells intrinsically release a factor that can directly activate monocytes to increase inflammation. The baseline inflammation seen in SCD has always been attributed to sequelae secondary to the sickling phenomenon. We show that PlGF contributes to the inflammation observed in SCD and increases the incidence of vaso-occlusive events.

Anemia, Sickle Cell↗
PubMed2002

A practical approach to neutrophil disorders.

This review discusses disorders of altered neutrophil number and function and provide a basic framework for patient evaluation and management. The sections begin with neutropenia, neutrophilia and neutrophil dysfunction with a general screening approach to differentiate common, more benign syndromes from rare, often more serious disorders. Also included is a detailed discussion of some specific primary neutrophil syndromes at the end of each section. Focus is placed on specific disorders that are clinically common or particularly instructive.

Humans↗