Seonwoo Kim

Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease.

Objective: The purpose of this study was to present the computed tomography (CT) findings of pulmonary artery sarcoma in 7 patients with a focus on the distinguishing features of pulmonary embolic disease. Methods: For the 9 years from December 1993 to November 2002, we treated 7 patients with pathologically proven pulmonary artery sarcoma, and during the 2 years from December 2000 to November 2002, we treated 40 patients with acute (n = 33) or chronic (n = 7) pulmonary embolism. In these patients, pulmonary embolism was diagnosed from serial CT or clinical findings. Two chest radiologists, blinded to the diagnoses, independently reviewed the scans of all 47 patients in random order, and the so-documented CT features of sarcoma and pulmonary embolism were compared by using Fisher exact test or the generalized estimating equations test. Results: The two most frequent CT findings of pulmonary artery sarcomas were a low-attenuation filling defect occupying the entire luminal diameter of the main (n = 1) or proximal (n = 6) pulmonary artery and an expansion of any segment of the pulmonary artery with extensive intraluminal filling defect, as observed in six (86%) of 7 patients. In contrast, the finding of a lesion occupying the entire luminal diameter at the level of proximal pulmonary arteries was absent in all 40 patients with pulmonary embolism (P < 0.0001) (κ = 0.9111). Expansion of the pulmonary arteries was seen in one (3%) of 40 patients with pulmonary embolism (P < 0.0001) (κ = 0.9108). Extraluminal extension was observed in 5 of 7 (71%) patients with sarcoma, but in no patient with an embolism (P < 0.0001) (κ = 0.8773). Conclusion: CT can help differentiate pulmonary artery sarcoma from pulmonary embolism by indicating a low-attenuation filling defect occupying the entire luminal diameter of the proximal or main pulmonary artery, expansion of the involved arteries, or extraluminal tumor extension.

Macrolide Treatment for Mycobacterium abscessus and Mycobacterium massiliense Infection and Inducible Resistance

RATIONALE Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. OBJECTIVES To compare the activity of CLR and AZM in experimental models. METHODS We compared the treatment efficacies of CLR and AZM and determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. MEASUREMENTS AND MAIN RESULTS In all tested M. abscessus isolates, a high level of inducible CLR resistance developed (minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P < 0.001). Whereas the AZM MIC increased on Day 14 (P < 0.01 versus Day 3), the level was significantly lower than the CLR MIC on Day 14 (P < 0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P < 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P < 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. CONCLUSIONS CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.

Host Inflammatory Response Predicts Survival of Patients With Epstein-Barr Virus-Associated Gastric Carcinoma

BACKGROUND & AIMS Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric carcinoma (GC) with a better survival rate than other GCs; most cases of LELC are associated with Epstein-Barr virus (EBV) infection. We investigated whether the survival advantage of LELC is related to the EBV infection itself or to associated inflammatory immune responses. METHODS From 1994 to 2008, 123 EBV-associated GCs were identified and compared with 405 EBV-negative GCs. EBV-associated GCs were subclassified, based on the pattern of host inflammatory immune responses, into 3 histologic subtypes: typical LELC (n = 53, 43.1%), Crohns disease-like lymphocytic reaction (CLR) (n = 52, 42.3%), and conventional adenocarcinoma (n = 18, 14.6%). Patients with curatively resected EBV-negative GC were controls. Univariate and multivariate analyses were used, with Bonferroni correction. RESULTS Patients with EBV-associated GC had tumors of proximal location, lower N stage (P < .0001), and lower T stage (P = .02) and were older than controls (P = .0003). Upon univariate analysis, patients with EBV-associated GC had longer survival times than controls (P < .004); this difference was not significant in a multivariate analysis with Cox proportional hazards. Stratification of EBV-associated GCs by host cellular immune responses showed that patients with LELC and LELC+CLR have significantly longer overall survival time (hazard ratio, 0.09 and 0.42, respectively) and disease-free survival (hazard ratio, 0.05 and 0.46, respectively; P < .02). CONCLUSIONS Prognosis of EBV-associated GCs depends on the patients inflammatory response. The definition of LELC should be expanded to include EBV-associated GCs with CLR because these have a prognosis similar to LELC.

Outcome of Arthroscopic Single-Bundle Versus Double-Bundle Reconstruction of the Anterior Cruciate Ligament: A Preliminary 2-Year Prospective Study

PURPOSE The purpose of this study was to compare the clinical results of arthroscopic single-bundle and double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS We designed a prospective study that included patients with an isolated ACL injury. From April 2004 to February 2007, of 147 patients who underwent ACL reconstruction, 113 were included in this study. We serially obtained clinical and radiologic data preoperatively and postoperatively. We compared preoperative data and data at 2 years postoperatively in patients who had undergone single-bundle ACL reconstruction versus patients who had undergone double-bundle ACL reconstruction. There were 50 single-bundle reconstructions and 63 double-bundle reconstructions. Anteroposterior stability was assessed objectively by anterior stress radiographs with the telos device (telos, Marburg, Germany) and the maximal manual test with the KT-2000 arthrometer (MEDmetric, San Diego, CA). Rotational stability was determined by lateral pivot-shift test. The clinical results were assessed by International Knee Documentation Committee and Orthopadische Arbeitsgruppe Knie scores and Tegner activity scale. In addition, we evaluated postoperative thigh circumference and range of motion. RESULTS Residual anteroposterior laxity determined at 2 years postoperatively by telos and KT-2000 was 1.74mm +/- 1.67mm and 1.79mm +/- 1.56mm, respectively, in the single-bundle reconstruction group and 1.63mm +/- 1.50mm and 1.61mm +/- 1.22mm, respectively, in the double-bundle reconstruction group. There were no statistically significant differences. For the lateral pivot-shift test done at 2 years postoperatively, there was no statistically significant difference. In addition, clinical results such as International Knee Documentation Committee score, Orthopadische Arbeitsgruppe Knie score, Tegner activity scale, thigh circumference, and range of motion showed no significant differences between the 2 groups. CONCLUSIONS Double-bundle reconstruction of the ACL by a method using 2 femoral tunnel and 2 tibial tunnels showed no differences in stability results or any other clinical aspects or in terms of patient satisfaction. LEVEL OF EVIDENCE Level II, prospective comparative study.

MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas

The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324–2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227–2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.

Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1.

The deletion (D) allele of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene is strongly associated with an increased level of circulating ACE. The ACE gene polymorphism may influence the production of angiotensin II (Ang II). It has been shown that Ang II modulates fibrinolysis, that is, Ang II increases plasminogen activator inhibitor-1 (PAI-1) mRNA and plasma PAI-1 levels in vitro and in vivo. Considered together, we tested the hypothesis that the deletion allele of the ACE gene might be associated with increased levels of PAI-1. We related the ACE genotype to PAI-1 antigen levels in 603 men and 221 women attending a routine health screening. As a whole, the plasma PAI-1 level was not strongly associated with ACE genotype. Since the PAI-1 level was significantly influenced by well-known risk factors for coronary artery disease (CAD), we further analyzed the data after excluding subjects with major cardiovascular risk factors. In low-risk male subjects, the DD genotype had significantly higher levels of plasma PAI-1 (DD: 20.3 +/- 2.2; DI: 13.9 +/- 1.1; II: 13.6 +/- 1.3 ng/mL, P = .010 by ANOVA). In low-risk female subjects, the DD genotype showed a tendency to a high level of plasma PAI-1 without statistical significance. When analysis was restricted to postmenopausal women (age > or = 55 or FSH > or = 35 ng/mL), the DD genotype showed a significantly higher level of PAI-1 than subjects with the DI and II genotypes (27.7 +/- 6.2 versus 15.6 +/- 1.8 ng/mL, P = .028). The DD polymorphism of the ACE gene is associated with high PAI-1 levels in male and possibly in postmenopausal female subjects who have lower conventional cardiovascular risk factors. These results suggest that the increased ACE activity caused by DD polymorphism may play an important role in elevating the level of plasma PAI-1. Our data support the notion that the genetic variation of ACE contributes to the balance of the fibrinolytic pathway.

Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: A randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVES:Esophageal hypersensitivity is currently believed to have a crucial role in the pathogenesis of functional chest pain (FCP). The aim of this study was to evaluate the clinical efficacy of venlafaxine, a serotonin–norepinephrine reuptake inhibitor (SNRI), for FCP in young adult patients.METHODS:Patients diagnosed with FCP were randomized to either an extended-release formulation of venlafaxine (75 mg hora somni) or a placebo for 4 weeks. After a washout period of 2 weeks, patients crossed over to the other arm of the study. The primary efficacy variable was the number of patients with >50% improvement in symptom scores. The secondary efficacy variables were (i) the symptom intensity score during each week, (ii) quality of life (QOL), (iii) the Beck Depression Inventory (BDI) score, and (iv) side effects.RESULTS:A total of 43 patients (37 men, mean age 23.5±1.9 years) completed the study. A positive response was observed in 52.0% of patients during venlafaxine treatment; 4.0% had a positive response with placebo treatment as assessed by the intention-to-treat analysis (venlafaxine vs. placebo: odds ratio 26.0; 95% confidence interval 5.7–118.8; P<0.001). Results of Short-Form 36 (SF-36) indicated that patients who received venlafaxine treatment had a significantly greater improvement in body pain and emotional role compared with those who received placebo treatment (P=0.002 and P=0.002, respectively). No significant change was noted in the depression score after venalafaxine or placebo treatment. One patient withdrew from the study because of sleep disturbance and loss of appetite while receiving venlafaxine.CONCLUSIONS:Venlafaxine, an SNRI antidepressant, significantly improved symptoms in young adult patients with FCP.

Serum melanotransferrin, p97 as a biochemical marker of Alzheimer's disease.

The protein melanotransferrin (p97) is associated with the brain lesions of Alzheimers disease (AD) and is a potential marker of the disorder. We measured serum p97 concentrations in 211 subjects: 71 patients with AD, 56 patients with non-AD-type dementia, and 84 normal control subjects. Serum p97 concentrations were elevated 3- to 4-fold in AD (median 15.00 pg/μl, interquartile range 10.20–17.00 pg/μl) as compared to non AD dementia (2.85 pg/μl, 1.93–7.15 pg/μl) and normal controls (3.20 pg/μl, 2.55–3.95 pg/μl). The mean elevation was significant at 13.54 ± 3.72 pg/μl, even in the 38 subjects with mild AD (CDR stage 0.5–1). Receiver operating characteristic analyses confirmed an optimal diagnostic threshold of 10.0 pg/μl, which yielded over-all accuracy of 0.882 to 0.915. Serum p97 is a candidate marker of AD, even in the early stage when clinical diagnosis is most uncertain.

Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients

INTRODUCTION Warfarin, a commonly prescribed anticoagulant, exhibits large interindividual and interethnic differences in the dose required for its anticoagulation effect. Asian patients require a much lower maintenance dose compared with Caucasians; the explanation for these differences remains unknown. METHODS We analyzed five single nucleotide polymorphisms of the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) and the *3 variant of cytochrome P450 (CYP)2C9, as well as the plasma warfarin concentration, in 108 Korean patients with atrial fibrillation. RESULTS Genotypic frequencies of VKORC1 +1173CT and CYP2C9*1/*3 were 17.6 and 10.2%, respectively, in the study population; VKORC1 +1173CC and CYP2C9*3/*4 were detected in one patient each. Patients carrying at least one copy of the VKORC1 +1173C allele, or the H7 (group B) haplotype, required a significantly higher warfarin dose (n = 20; 5.5 +/- 1.7 mg/day) than those homozygous for the +1173T allele, or the H1 (group A) haplotype, (3.8 +/- 1.2 mg/day; p < 0.001). There were statistically significant differences in warfarin dose between the CYP2C9*1/*1 (4.3 +/- 1.6 mg/day; p < 0.001) and those with the other two genotypes including CYP2C9*1/*3 and CYP2C9*3/*4 (2.7 +/- 0.9 mg/day). The multiple regression analysis revealed that the VKORC1 genotype (r2 = 0.197; p < 0.001), the age when warfarin started (r2 = 0.09; p < 0.001), body surface area (r2 = 0.041; p = 0.004) and CYP2C9 genotype (r2 = 0.029; p = 0.014) were factors associated with the daily dose of warfarin required. CONCLUSION In the present study, we found that the VKORC1 polymorphism had a dominant genetic influence on interindividual variability for warfarin dose in Korean patients. It explained approximately 32% of the overall variability in warfarin dose requirements given all of the variables studied. Thus, analysis of the VKORC1 genotypes may be important to guide warfarin dose selection and allow personalized warfarin treatment.

Thin-Section CT Findings of Nontuberculous Mycobacterial Pulmonary Diseases: Comparison Between Mycobacterium avium-intracellulare Complex and Mycobacterium abscessus Infection

We aimed to compare the CT findings of nontuberculous mycobacterial pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. Two chest radiologists analyzed retrospectively the thin-section CT findings of 51 patients with MAC and 36 with M. abscessus infection in terms of patterns and forms of lung lesions. No significant difference was found between MAC and M. abscessus infection in the presence of small nodules, tree-in-bud pattern, and bronchiectasis. However, lobar volume decrease (p=0.001), nodule (p=0.018), airspace consolidation (p=0.047) and thin-walled cavity (p=0.009) were more frequently observed in MAC infection. The upper lobe cavitary form was more frequent in the MAC (19 of 51 patients, 37%) group than M. abscessus (5 of 36, 14%) (p=0.029), whereas the nodular bronchiectatic form was more frequent in the M. abscessus group ([29 of 36, 81%] vs. [27 of 51, 53%] in MAC) (p=0.012). In conclusion, there is considerable overlap in common CT findings of MAC and M. abscessus pulmonary infection; however, lobar volume loss, nodule, airspace consolidation, and thin-walled cavity are more frequently seen in MAC than M. abscessus infection.