Biomedical subjects

John Kim

Publications and source records attributed to John Kim.

At least 19 recordsLinked to original sources

PubMed2007

Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy.

OBJECTIVE: To evaluate attentional and activity behaviors in 4-year-olds following prenatal selective serotonin reuptake inhibitor (SSRI) exposure. DESIGN: Prospective cohort design. SETTING: Tertiary care center. PARTICIPANTS: Twenty-two 4-year-olds with prolonged prenatal SSRI medication exposure and 14 children without prenatal exposure. MAIN EXPOSURE: Prenatal SSRI exposure. MAIN OUTCOME MEASURES: Group differences in externalizing behaviors (according to the Child Behavior Checklist) and direct observations of child attention, activity, and impulsiveness in a laboratory setting using the procedure by Crowell and colleagues were compared, including measures of the duration of prenatal SSRI exposure, umbilical cord drug levels, a history of poor neonatal adaptation, and maternal mood. RESULTS: Externalizing behaviors did not differ between groups. Maternal depression and anxiety at the 4-year follow-up were associated with increased reports of externalizing behaviors. Increased externalizing behaviors were associated with increased umbilical cord drug levels (F(1,34) = 6.3; P = .02), but when controlling for maternal depressed mood at the 4-year follow-up, such levels only accounted for 11.2% of the behavioral outcomes (P>.05). On direct observation, the persistence score for child behavior was significantly lower in the exposed group. Increased aggressiveness scores were associated with a history of poor neonatal adaptation, even when parental report of stress was added to the model (F(1,34) = 4.0; P = .03); however, neither parental report of stress nor poor neonatal adaptation were significant (both P = .09), suggesting that both are important, if not unique, predictors of child behavior. CONCLUSIONS: These findings suggest that the best predictors of externalizing behaviors at age 4 years are current maternal mood and parental stress, regardless of prenatal depressed mood and SSRI treatment during pregnancy. It remains uncertain whether poor neonatal adaptation can be excluded as a possible predictor of externalizing behaviors.

Adult↗

PubMed2006

Pelvic MRI in children with Crohn disease and suspected perianal involvement.

MRI is an important imaging tool in evaluation of adult and pediatric patients with Crohn disease. Pelvic MRI, in particular, has become the method of choice to evaluate for perianal fistulas and associated complications of Crohn disease. MRI can define the extent and location of perianal fistulas and abscesses, as well as provide critical information for operative management. In this pictorial essay, we describe useful MRI techniques for evaluation of perianal complications in pediatric patients with Crohn disease. We review pertinent anatomy and illustrate typical examples of perianal fistulas with and without abscess. We show one case of clinically suspected perianal fistula that was actually a pilonidal sinus.

Child↗

PubMed2006

East-West Symposium on nasopharyngeal cancer.

BACKGROUND: To achieve greater understanding of the epidemiology, pathogenesis, molecular oncology, diagnostic, and therapeutic aspects of nasopharyngeal cancer (NPC), an international meeting was held in June 2005, Toronto, Canada. RESULTS: Further insights were obtained into the role of EBV in NPC development, with its diverse effects ranging from proliferative signals via NF-kB, to immunesuppression, to angiogenic gene regulation. Subsequently, multiple pathways are dysregulated in NPC as revealed by expression array analyses, including apoptosis, integrin, and B-catenin cascades. Advances have been made in the diagnosis and monitoring of NPC, using transoral brushings and plasma levels of EBV transcripts, which may not directly correlate with the number of circulating tumor cells, but is nevertheless informative in predicting and tracking disease response. Many novel therapies have promising results, particularly in the areas of immunotherapies, and the exploration of molecularly targeted approaches such as cetuximab or histone deacetylase inhibitors. CONCLUSIONS: The results from large randomized trials and meta-analyses have consistently demonstrated the benefit of concurrent chemotherapy with curative radiation therapy, but at a cost of greater acute and late-tissue toxicities. Further advances are required to achieve an improved understanding on the inter-relationship between environmental and genetic determinants in NPC development, to reduce the global burden of this disease. At the same time, novel therapeutic approaches are necessary to increase curability of NPC, but with reduced long-term toxicities.

Epstein-Barr Virus Infections↗

PubMed2006

Reduction of right medial pulvinar volume and neuron number in schizophrenia.

Several studies have described a reduction of pulvinar volume and/or neuronal number in schizophrenia (SZ). In order to better localize these changes, we assessed volume and neuronal number of the pulvinar and several of its subdivisions in postmortem material from subjects with chronic SZ and subjects with no psychiatric history. Total pulvinar volume and neuronal number were significantly lower in SZ and these differences were significant in only in its medial division. The medial pulvinar interconnects various heteromodal cortical regions suggesting that these deficits may contribute to the abnormalities of higher order integrative functions characteristic of schizophrenia.

Aged↗

PubMed2006

Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists.

In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo[2.2.2]octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A1, A2A, A2B, and A3 receptors are presented. Bicyclo[2.2.2]octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/kg po). Optimization of the bridgehead substituent led to propionic acid 29 (BG9928), which retained high potency (hA1, Ki=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.

Adenosine A1 Receptor Antagonists↗

PubMed2006

Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling.

Gene expression profiling was conducted using primary human nasopharyngeal carcinoma (NPC) biopsy samples to improve the understanding of the molecular pathways defining NPC and to identify novel potential therapeutic targets. RNA samples were extracted from 36 patients suspected to have NPC and hybridized onto the Affymetrix U133A chip. NPC was diagnosed in 19 patients, 11 had lymphoid hyperplasia (LH), and 6 were "normal" biopsies. Clinical stages for these NPC patients ranged from I-IV, including one M1. All NPC patients (except the M1) were treated with curative intent, which included radiotherapy alone (4 patients), or combined with chemotherapy (14 patients). Unsupervised clustering demonstrated a distinct NPC expression pattern, compared to normal biopsies. Subsequent Significance Analysis of Microarrays (SAM) derived from 14 NPC and 6 normal samples discovered 1,089 differentially regulated genes. Pathway analyses revealed novel insights into the mechanisms leading to NPC, whereby upregulation of NFkappaB2 and survivin play central roles in increasing resistance to apoptosis, and changes in integrin and WNT/beta-catenin signaling leading to uncontrolled proliferation. The role of survivin in resisting apoptosis in NPC was confirmed by RNA interference. Our data provide novel insights into the development and progression of NPC, and suggest survivin as a novel therapeutic target for NPC.

Apoptosis↗

PubMed2006

Mycobacterium tuberculosis DeltaRD1 DeltapanCD: a safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis.

The global epidemic of tuberculosis (TB), fueled by the growing HIV pandemic, warrants the development of a safe and effective vaccine against TB. We report the construction and characterization of an unlinked double deletion mutant of Mycobacterium tuberculosis H37Rv that deletes both the primary attenuating mutation of BCG (DeltaRD1) and two genes required for the synthesis of pantothenate (DeltapanCD). The M. tuberculosis DeltaRD1 DeltapanCD (mc(2)6030) mutant undergoes limited replication in mice, and yet is both significantly safer than BCG in immunocompromised mice and also safe in guinea pigs. Additionally, the mc(2)6030 strain does not reactivate in a mouse chemo-immunosuppression model. Importantly, long-lived protective immune responses following immunization with the mc(2)6030 strain prolong the survival of wild type mice, and CD4-deficient mice against an aerosol challenge with virulent M. tuberculosis. Given its overall safety and effectiveness, the mc(2)6030 live attenuated strain should be considered as a human vaccine candidate for protecting both healthy and HIV-infected individuals against TB.

Animals↗

PubMed2006

Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency.

CONTEXT: LB03002 is a novel sustained-release GH preparation administered once weekly. OBJECTIVE: Our objective was to examine the pharmacokinetics, pharmacodynamics, and safety of LB03002 vs. daily GH. DESIGN AND SETTING: This open-label, crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH. PATIENTS AND OTHER PARTICIPANTS: Six male and three female patients with adult GH deficiency participated in the single-center study. INTERVENTION: Subjects were on stable daily GH treatment before the study. After a 4-wk washout with no GH, five weekly doses of LB03002 were given. MAIN OUTCOME MEASURE: GH and IGF-I concentrations were measured during the last dose of daily GH and during the first and fifth weekly doses of LB03002. RESULTS: The observed maximal serum GH concentration was approximately doubled after LB03002 (6.1 +/- 3.2 and 4.5 +/- 2.2 microg/liter at first and fifth doses) compared with daily GH (2.7 +/- 2.2 microg/liter). A sustained increase in GH concentration for more than 48 h was observed with LB03002, such that dose-normalized area under the curve (AUC) was not significantly different between daily GH and LB03002. Mean maximal serum IGF-I concentration was 34-41% greater with LB03002 than with daily GH, and AUC was 7-fold greater. However, normalized to GH dose, AUC for IGF-I was comparable. Adverse events and local reactions were acceptable, and there were no evident safety concerns with LB03002. CONCLUSIONS: Multiple weekly doses of LB03002 appeared safe and well tolerated. Comparable GH bioavailability and sustained IGF-I elevations support the use of once-weekly LB03002 to replace daily GH therapy.

Adult↗

PubMed2006

Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases.

BACKGROUND: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). METHODS AND MATERIALS: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. RESULTS: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. CONCLUSION: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

Adenocarcinoma↗

PubMed2006

Spinal cord planning risk volumes for intensity-modulated radiation therapy of head-and-neck cancer.

PURPOSE: To assess planning organ at risk volume (PRV) margins of the spinal cord in intensity-modulated radiotherapy (IMRT) of oropharyngeal cancers, by modeling the effect of geometric uncertainties to estimate the probability of the spinal cord receiving a particular dose. METHODS AND MATERIALS: Five patients with oropharyngeal cancer were treated by IMRT with simultaneous doses of 66 Gy (gross disease) and 54 Gy (subclinical disease) in 30 fractions. Spinal cord doses were limited to 45 Gy. The probability, due to random and systematic patient positioning uncertainties (3-mm standard deviation), of the cord receiving a particular dose was determined. The effect of an on-line setup correction protocol was also modeled. RESULTS: The mean probability of a maximum spinal cord dose of 45 Gy was 1%, with a 6-mm PRV margin. The mean probability of a maximum dose exceeding 40 Gy was 37% (range, 13-77%); this probability is reduced with a setup correction protocol. CONCLUSION: A spinal cord PRV generated with a 6-mm margin leads to a 99% probability of maintaining the maximum spinal cord dose below 45 Gy. The application of an on-line setup correction protocol reduces the cord dose by approximately 5 Gy.

Dose Fractionation, Radiation↗

PubMed2006

Pharmacokinetics of a ginseng saponin metabolite compound K in rats.

The absorption, dose-linearity and pharmacokinetics of compound K, a major intestinal bacterial metabolite of ginsenosides, were evaluated in vitro and in vivo. Using the Caco-2 cell monolayers, compound K showed moderate permeability with no directional effects, thus suggesting passive diffusion. After intravenous dose (i.v.; 1, 2, and 10 mg/kg), no significant dose-dependency was found in Cl (17.3-31.3 ml/min/kg), Vss (1677-2744 ml/kg), dose-normalized AUC (41.8-57.8 microg.min/ml based on 1 mg/kg) and t1/2. The extent of urinary excretion was minimal for both i.v. and oral doses. The extent of compound K recovered from the entire gastrointestinal tract at 24h were 24.4%-26.2% for i.v. doses and 54.3%-81.7% for oral doses. Following oral administration (doses 5-20 mg/kg), dose-normalized AUC (based on 5 mg/kg) was increased at the 20 mg/kg dose (85.3 microg.min/ml) compared with those at lower doses (4.50-10.5 microg.min/ml). Subsequently, the absolute oral bioavailability (F) was increased from 1.8%-4.3% at the lower doses to 35.0% at the 20 mg/kg dose. The increased F could be related to the saturation of carrier-mediated hepatic uptake and esterification of compound K with fatty acids in the liver.

Administration, Oral↗

PubMed2006

Pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats.

This study is the first report of the pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats after i.v. and oral administration. Apicidin was injected intravenously at doses of 0.5, 1.0, 2.0 and 4.0 mg/kg. The terminal elimination half-life (t1/2), systemic clearance (Cl) and steady-state volume of distribution (Vss) remained unaltered as a function of dose, with values in the range 0.8-1.1 h, 59.6-68.0 ml/min/kg and 2.4-2.7 l/kg, respectively. Whereas, the initial serum concentration (C0) and AUC increased linearly as the dose was increased. Taken together, the pharmacokinetics of apicidin were linear over the i.v. dose range studied. The extent of urinary and biliary excretion of apicidin was minimal (0.017%-0.020% and 0.049% +/- 0.016%, respectively). Oral pharmacokinetic studies were conducted in fasting and non-fasting groups of rats at a dose of 10 mg/kg. The Tmax, Cl/F and Vz/F were in the range 0.9-1.1 h, 520.3-621.2 ml/min/kg and 67.6-84.4 l/kg, respectively. No significant difference was observed in the oral absorption profiles between the two groups of rats. Apicidin was poorly absorbed, with the absolute oral bioavailability of 19.3% and 14.2% in fasting and non-fasting rats.

Administration, Oral↗

PubMed2006

PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis.

BACKGROUND: Few investigations have described fracture risk and its relation to disorders in calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) metabolism in the end-stage renal disease population. METHODS: Laboratory values for Ca, P, and PTH were obtained from Dialysis Morbidity and Mortality Study (DMMS) Waves 1 to 4. Additional data available from the US Renal Data System were used to determine the incidence and associated costs of hip, vertebral, and pelvic fractures in 9,007 patients with nonmissing laboratory values and Medicare as primary payor. Cox proportional hazards and Poisson models were used to analyze time to first fracture and numbers of fractures, respectively. RESULTS: There was no association between Ca or P values and risk for fracture; risks for vertebral and hip fractures and PTH concentrations were U shaped and weakly significant using Poisson regression (P = 0.03). The age- and sex-adjusted mortality rate after fracture was 2.7 times greater (580/1,000 person-years) than for general dialysis patients from the DMMS (217/1,000 person-years). Mean total episodic costs of hip, vertebral, and pelvic fractures were 20,810 dollars +/- 16,743 dollars (SD), 17,063 dollars +/- 26,201 dollars, and 14,475 dollars +/- 19,209 dollars, respectively. CONCLUSION: Using data from the DMMS, there were no associations between Ca and P concentrations and risk for fracture. Risks for hip and vertebral fracture were associated weakly with PTH concentration, with the lowest risk observed around a PTH concentration of 300 pg/mL (ng/L). Fractures were associated with high subsequent mortality and costs. Prospective studies are needed to determine whether therapies that maintain PTH concentrations within or near the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative range will result in fewer complications of disordered mineral metabolism.

Aged↗

PubMed2006

A pilot study using high-fidelity simulation to formally evaluate performance in the resuscitation of critically ill patients: The University of Ottawa Critical Care Medicine, High-Fidelity Simulation, and Crisis Resource Management I Study.

OBJECTIVE: Resuscitation of critically ill patients requires medical knowledge, clinical skills, and nonmedical skills, or crisis resource management (CRM) skills. There is currently no gold standard for evaluation of CRM performance. The primary objective was to examine the use of high-fidelity simulation as a medium to evaluate CRM performance. Since no gold standard for measuring performance exists, the secondary objective was the validation of a measuring instrument for CRM performance-the Ottawa Crisis Resource Management Global Rating Scale (or Ottawa GRS). DESIGN: First- and third-year residents participated in two simulator scenarios, recreating emergencies seen in acute care settings. Three raters then evaluated resident performance using edited video recordings of simulator performance. SETTING: A Canadian university tertiary hospital. INTERVENTIONS: : The Ottawa GRS was used, which provides a 7-point Likert scale for performance in five categories of CRM and an overall performance score. MEASUREMENTS AND MAIN RESULTS: Construct validity was measured on the basis of content validity, response process, internal structure, and response to other variables. One variable measured in this study was the level of training. A t-test analysis of Ottawa GRS scores was conducted to examine response to the variable of level of training. Intraclass correlation coefficient scores were used to measure interrater reliability for both scenarios. Thirty-two first-year and 28 third-year residents participated in the study. Third-year residents produced higher mean scores for overall CRM performance than first-year residents (p < .0001) and in all individual categories within the Ottawa GRS (p = .0019 to p < .0001). This difference was noted for both scenarios and for each individual rater (p = .0061 to p < .0001). No statistically significant difference in resident scores was observed between scenarios. Intraclass correlation coefficient scores of .59 and .61 were obtained for scenarios 1 and 2, respectively. CONCLUSIONS: Data obtained using the Ottawa GRS in measuring CRM performance during high-fidelity simulation scenarios support evidence of construct validity. Data also indicate the presence of acceptable interrater reliability when using the Ottawa GRS.

Adult↗

PubMed2006

A population-based approach to determine the prevalence of transmitted drug-resistant HIV among recent versus established HIV infections: results from the Canadian HIV strain and drug resistance surveillance program.

OBJECTIVES: Published results on primary or transmitted HIV drug resistance may be biased because they have been largely derived from specific cohort studies or higher risk individuals who present symptomatically. Here, we present results from a representative population-based study of newly diagnosed cases of HIV in Canada and compare the prevalence of transmitted drug resistance between recent and established infections. METHODS: Available archived sera taken for the purpose of diagnostic HIV testing from all treatment-naive HIV-positive individuals who were newly diagnosed between 2000 and 2001 were tested for recency of infection, HIV-1 subtype, and mutations conferring reduced susceptibility to reverse transcriptase inhibitors and protease inhibitors (PIs). Recent infections were identified using the Organon Teknika Vironostika HIV-1-LS assay. After full-length sequencing of the pol gene, drug resistance mutations were identified using the 2004 International AIDS Society-USA mutations panel. Differences in drug resistance profiles between recent and prevalent infections were examined using the chi test and the Fisher exact test. The variables examined included gender, age at diagnosis, year of diagnosis, exposure category, ethnicity, and HIV-1 subtype. RESULTS: Among the study population, 8.1% had genotypic evidence of transmitted drug resistance: 4.1% against nucleoside reverse transcriptase inhibitors, 1.4% against nonnucleoside reverse transcriptase inhibitors, 1.5% against PIs, and 1% against > or =2 classes of drugs. A higher proportion of recent infections had genotypic evidence of transmitted drug resistance when compared with established infections (12.2% vs. 6.1%, respectively; P = 0.005). Transmitted drug resistance was identified mainly among recently infected Caucasian men who have sex with men but it was not limited to this group. Compared with the year 2000, a higher proportion of recently infected individuals with resistance-conferring mutations were diagnosed during the year 2001 (66.7% vs. 46.6%). CONCLUSIONS: In Canada, transmitted drug resistance is occurring within all 3 drug classes and across different population groups. The results suggest that the prevalence rates may be higher among recent versus established infections. Given the public health implications of transmitting drug-resistant HIV, it is important to continue population-based drug resistance surveillance to guide optimum prevention and treatment of HIV infection.

Adult↗

PubMed2006

Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast-feeding.

AIMS: To compare the disposition of fluoxetine and norfluoxetine enantiomers in the mother, foetus and infant. METHODS: Blood from pregnant women taking fluoxetine (n = 9), during pregnancy was sampled in the third trimester and at delivery (maternal and cord venous blood), and from the infants 48 h after delivery. The subset of these women who were breastfeeding, plus additional subjects recruited in the postpartum period, were studied further, and maternal and infant blood, and breast milk was sampled between 6 days and 11 months (n = 23). Drug and metabolite concentrations were measured using gas chromatography/mass spectrometry or liquid chromatography, tandem mass spectrometry. RESULTS: There was a high correlation between maternal and foetal (cord blood) fluoxetine and norfluoxetine enantiomers (r(2)-0.9), the mean foetal/maternal ratios (95% confidence intervals) being 0.91 (0.61, 1.02) and 1.04 (0.93, 1.05), for fluoxetine and norfluoxetine, respectively. In 2 day old infants exposed to the drug in utero, the fluoxetine and norfluoxetine plasma concentrations were the same as in cord blood at delivery. Over the next 2 months, the plasma concentrations in the infants fell progressively. Stereoselective disposition of both the drug and metabolite in the mother, foetus, infant and breast milk was observed. The S : R ratios in the foetus and newborn ( approximately 3) were significantly higher than in the serum ( approximately 2) or breast milk ( approximately 1.9) of the mothers, resulting in greater exposure of the foetus and infants to the biologically active enantiomers, particularly S-norfluoxetine. CONCLUSIONS: Foetal and infant exposure to fluoxetine and norfluoxetine is enhanced by their stereoselective disposition in the mother, foetus, breast milk and infant. Increased exposure may also result from decreased metabolism of the drug in the foetus and neonate.

Adult↗

PubMed2006

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE: Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS: Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS: Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION: On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.

Adult↗

PubMed2006

Comparison of lymphotropic nanoparticle-enhanced MRI sequences in patients with various primary cancers.

OBJECTIVE: This study was performed to empirically evaluate T2-weighted fast spin-echo, moderately T2*-weighted gradient-refocused echo (GRE), and heavily T2*-weighted GRE sequences to determine which sequence is the most effective for nodal characterization on lymphotropic nanoparticle-enhanced MRI (LNMRI). MATERIALS AND METHODS: The study included 65 patients who had proven primary cancer and were scheduled for either surgical lymph node dissection or imaging-guided lymph node biopsy. All patients underwent LNMRI using T2-weighted fast spin-echo, moderately T2*-weighted GRE, and heavily T2*-weighted GRE sequences. Unequivocal correlation of histopathology and MRI could be made in 140 nodes and only these were included in the analysis. Two blinded reviewers performed qualitative analysis of the nodes. Alternative free-response receiver operating characteristic (ROC) curves with a continuous rating scale were plotted for each sequence for both reviewers and the diagnostic accuracy of fast spin-echo T2-weighted and GRE T2*-weighted images were compared by calculating the area under the curve (A(Z)). A two-tailed Student's t test was performed to test the significance (p < 0.05) of the differences between the ROC curves derived from the three sequences. RESULTS: Irrespective of reviewer experience, T2*-weighted sequences showed better nodal characterization when compared with T2-weighted sequences. For both reviewers, there was a statistically significant difference between the A(Z) for T2- and the two T2*-weighted sequences (p < 0.05). Neither reviewer showed a statistically significant difference between the two T2*-weighted sequences. CONCLUSION: GRE T2*-weighted sequences are superior for nodal characterization on LNMRI to fast spin-echo T2-weighted sequences. Imaging protocols for LNMRI should include fast spin-echo T2-weighted imaging for anatomic localization, but characterization of nodes should be based on their appearance on contrast-enhanced T2*-weighted images. The T2*-weighted images acquired with dual TE values, one of which is intermediate and the other longer, improve nodal characterization.

Adult↗