First-trimester maternal plasma concentrations of C-reactive protein in low-risk patients and the subsequent development of chorioamnionitis

Baseline elevations of C-reactive protein (CRP) during pregnancy have been associated with adverse outcomes, including preterm delivery. Acute elevations have also been associated with intrauterine infections. The relationship between chronic, baseline elevations of CRP and histological chorioamnionitis, however, has not previously been explored. A nested case-control study was performed within a prospective observational cohort of low-risk patients seeking prenatal care. CRP was measured from maternal plasma collected before 13 weeks of estimated gestational age. Cases were defined by histological chorioamnionitis, and controls were selected randomly from patients without chorioamnionitis. We identified 36 cases of chorioamnionitis. There were no significant differences (p=0.64) in CRP concentrations between cases and controls. CRP concentrations remained nonsignificant in a logistic regression model that incorporated prepregnancy body mass index, placental weight, race, and gestational age at delivery (p=0.72). We concluded that the development of histological chorioamnionitis is not associated with elevations in maternal plasma CRP earlier in pregnancy.     

Prediction of Pathology and Survival by FDG PET in Gliomas

Objectives: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-d-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. Methods: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. Results: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for >1 year (median survival of 28 months) and 19% survived for >5 years. Only 29% (48/165) of patients with high uptake survived for >1 year, (median survival of 11 months) and none survived for >5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. Conclusions: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.     

Functional imaging of a large demyelinating lesion.

PURPOSE: To determine the metabolic characterization of a large solitary demyelinating lesion. METHODS: Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies with 2-deoxy-2-[F-18]fluoro-d-glucose (FDG), carbon-11-methionine (methionine) and carbon-11-choline (choline) were done on the demyelinating lesion. RESULTS: The demyelinating lesion exhibited a low glucose uptake, prominent methionine uptake and a minimal choline uptake on the PET studies. MRS data revealed an increased choline to creatine (cho/cr) ratio and a decreased N-acetyl-aspartate to creatine (NAA/cr) ratio, which demonstrated a return to near normal ratios on follow-up study. CONCLUSION: The report summarizes the metabolic characteristics of a demyelinating plaque.     

Retrovirus-mediated transfer of human alpha-galactosidase A gene to human CD34+ hematopoietic progenitor cells

Fabry disease, caused by a deficiency of lysosomal enzyme alpha-galactosidase A (alpha-gal A), is one of the inherited disorders potentially treatable by gene transfer to hematopoietic stem cells. In this study, a high-titer amphotropic retroviral producer cell line, MFG-alpha-gal A, was established. CD34+ cells from normal umbilical cord blood were transduced by centrifugal enhancement. The alpha-gal A activity in transduced cells increased 3.6-fold above the activity in nontransduced cells. Transduction efficiency measured by PCR for the integrated alpha-gal A cDNA in CFU-GM colonies was in the range of 42-88% (average, 63%). The expression of functional enzyme in TFI erythroleukemia was sustained for as long as cells remained in culture (84 days) and for 28 days in LTC-IC cultures of CD34+ cells. The ability of the transduced CD34+ cells to secrete the enzyme and to correct enzyme-deficient Fabry fibroblasts was assessed by cocultivation of these cells. The enzyme was secreted into the medium from transduced CD34+ cells and taken up by Fabry fibroblasts through mannose 6-phosphate receptors. These findings suggest that genetically corrected hematopoietic stem/progenitor cells can be an enzymatic source for neighboring enzyme-deficient cells, and can potentially be useful for gene therapy of Fabry disease.     

A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma.

PURPOSE: The goal of this investigation was to evaluate uptake and incorporation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG), 11C-methionine, and 11C-choline in 17 patients suspected of grade-II and grade-III tumors using positron emission tomography (PET) and use in vitro astrocytoma cell lines in order to support in vivo findings. METHODS: Seventeen patients with suspected astrocytomas (9 grade-II and 8 grade-III) were studied by PET with FDG and 11C-methionine; and one patient (grade-III) with FDG, 11C-methionine and 11C-choline. Uptake of PET molecular imaging probe was quantitative based on tumor to corresponding contralateral-region uptake ratio, tumor to mean-cortical-uptake ratio, and tumor to white matter uptake ratio. This was correlated with World Health Organization histology grading system and clinical follow-up. Uptake and incorporation of 3H-methionine, 3H-choline and FDG into lipid, RNA, DNA, and protein were investigated in a grade-III human tumor brain-14 astrocytoma cell line. RESULTS: A time-dependent increase in the total uptake of 3H-methionine, 3H-choline and FDG was observed in human tumor brain-14 astrocytoma-III cell line. 3H-methionine was incorporated predominantly into proteins (in excess of 40% at 1 h) while 3H-choline incorporated primarily into lipids (in excess of 60% at 1 hr). Total uptake of FDG was accounted for in the free-pool supernatant fraction. In all patients, PET images of 11C-methionine and FDG provided higher tumor to white matter ratios than tumor to corresponding contra-lateral region ratios and tumor to mean cortical uptake ratios. In grade II patients, FDG did not exhibit significant increase in tumor uptake, while 11C-methionine was a good predictor with ratios of approximately 1.50 +/- 0.48. In grade III patients, both FDG and 11C-methionine exhibited higher ratios than for grade II, with 11C-methionine being the greatest (ratios of 2.50 +/- 0.85), possibly suggesting enhanced protein synthesis. With respect to tumor delineating potential, 11C-choline may be equal to or slightly better than 11C-methionine in the subject evaluated with all three probes. CONCLUSIONS: Results suggest that a combination of FDG and 11C-methionine is useful in the prediction of histological grade of astrocytomas. In addition, 11C-methionine is better than FDG in delineating tumor boundary for low-grade gliomas. In vitro results suggest that 3H-methionine is significantly incorporated into proteins and provides the major driving force in the uptake of 11C-methionine observed in PET images.     

Cortical dysplasia localized by [11C]methionine positron emission tomography: case report

Numerous functional neuroimaging techniques have progressively been added to the presurgical evaluation of refractory partial epilepsies. These investigations can help confirm the origin of seizure onset previously suggested by MR imaging and electro-clinical data, provide independent prognostic information, and provide critical diagnostic value when MR imaging results are strictly normal or show multifocal abnormalities. Of the various functional neuroimaging modalities, [11C]methionine positron emission tomography for methionine uptake into seizure foci is still in the preliminary stages of investigation. A single case of medically intractable epilepsy with focal cortical dysplasia documented by [11C]methionine positron emission tomography and possible hypotheses to explain the methionine uptake into the seizure focus are described below.     

Maternal and fetal C-reactive protein genotype and first trimester CRP concentrations in maternal plasma

Maternal plasma CRP concentrations in pregnancy are increased over pre-pregnancy values and high concentrations have been associated with adverse obstetrical outcomes. The objective of this study was to explore the relationship between maternal and fetal variation in C-reactive protein (CRP) genotype and maternal plasma CRP concentrations in the first trimester in low risk patients. DNA was extracted from maternal and cord blood of subjects in a prospective observational cohort. Single-nucleotide polymorphism (SNP) selection was made using a linkage disequilibrium bin approach. CRP concentrations were measured in first trimester maternal plasma using an enzyme-linked immunosorbent assay (ELISA) kit. Kruskal-Wallis rank testing was used to analyze genetic and clinical determinants of CRP concentrations. Genotype results were available in 190 mother-baby pairs. There was no significant difference in CRP concentration among maternal or fetal CRP genotypes. Thus, first trimester concentrations of maternal plasma CRP in low risk subjects do not appear to be significantly associated with CRP genotype. Instead, differences in clinical factors probably have more influence on baseline maternal CRP concentrations.     

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.