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People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 μg/dL, 1.42 μg/L, and 1.66 μg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33-Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural necrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early‐period antiarrhythmic effects induced by high‐dose irradiation are unknown. This study investigated dose‐responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild‐type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks’ postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high‐dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose‐responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell–related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high‐dose irradiation. ECG indicated intracardiac conduction delay with prominent ST‐segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

This study compares the heavy metal exposure levels of the population of abandoned metal mines, with high risks of environmental pollution and health effects. We used data from a two-stage abandoned metal mines survey (AMS, n = 4467). The Korea National Health and Nutrition Examination Survey (KNHANES) and the Korea National Environmental Health Survey (KNEHS) were used as general population data. Based on the sex and age distribution in the AMS, a simple random sampling was performed, so that the two datasets had the same distribution (KNHANES n = 1815, KNEHS n = 2328). Blood lead concentrations were slightly higher in the AMS than in KNEHS. Blood cadmium concentrations were similar between the two groups. However, the difference in urine cadmium concentrations was pronounced and statistically significant. Moreover, 30.6% of the AMS data for urine cadmium concentration exceeded the 95th percentile of the KNEHS data. The concentration of lead and cadmium in the residents of the abandoned metal mines, i.e., the vulnerable regions, was higher than that in the general population. It is necessary to monitor and manage the vulnerable regions via a more active and extensive survey system.

Thermo-sensitive injectable hydrogels that spontaneously react to physiological temperature have been widely studied to be used in biomedical fields. However, several challenges on their unstable structures with large-sized pores and low mechanical strength under physiological conditions must be addressed to enable their practical applications. We synthesized the hydroxybutyl methacrylated chitosan (HBC-MA) hydrogel that possesses both thermo-sensitive and photo-crosslinkable properties. The HBC-MA showed effective sol-gel transition under physiological temperature as well as a sensitive photo-crosslinkable property with visible light capable of skin penetration. The co-nonsolvency property and thermo-sensitivity of HBC-MA prevented unintended loss of the hydrogel graft after being subcutaneously injected in mice. Subsequently applied visible light on the skin beneath which the hydrogel was injected significantly improved the mechanical strength and stability of the graft. The injectable HBC-MA hydrogel developed in this study can be applicable to a wide range of biomedical fields such as drug delivery system and tissue engineering.

A significant relationship between arsenic exposure and non-melanoma skin cancer (NMSC) is well known. The toxicity of arsenics which develop NMSC is dependent on their species. Accordingly, total arsenic levels are unreliable for risk assessment of NMSC. However, there are few studies on quantitative exposure assessment of arsenic species in NMSC patients. To validate the contribution of each arsenic species to NMSC, we compared the creatinine-adjusted urinary concentration of arsenic species in NMSC patients and community controls. A total of 124 biopsy-proven NMSC cases and 125 age- and sex-matched community controls, drinking tap water with low-level arsenic concentration (

Background Adults with unoperated congenitally corrected transposition of the great arteries are rare but form a distinct group among adults with congenital heart disease. Patients with congenitally corrected transposition of the great arteries often have one or more associated cardiac anomalies that dictate the need for, and timing of, surgical intervention in childhood. However, in a proportion of patients, the hemodynamics does not require surgical attention during childhood, and, in some patients, a correct diagnosis is not established until adulthood. Here we report an adult case of unoperated congenitally corrected transposition of the great arteries with a large ventricular septal defect and probable pulmonary arterial hypertension. Case presentation Our patient was a 46-year-old Korean man. Transthoracic echocardiography and cardiac catheterization demonstrated hemodynamically balanced ventricles with a non-regurgitant systemic atrioventricular valve, normal pulmonary arterial pressure, and a reasonable difference between the oxygen saturation values of the aorta and pulmonary trunk, even with the presence of a large ventricular septal defect. Further morphological assessments using cardiac computed tomography and three-dimensional modeling/printing of his heart revealed that the mitral valve was straddling over the posteriorly positioned ventricular septal defect, which could explain the functional and anatomical subvalvular pulmonary stenosis and a small amount of shunt flow through the large ventricular septal defect. We interpreted this combination of cardiac defects as able to sustain his stable cardiac function. Thus, we decided to maintain his unoperated status. Conclusion A detailed anatomical understanding based on transthoracic echocardiography, cardiac computed tomography, and three-dimensional printing can justify a decision to not operate in cases of congenitally corrected transposition of the great arteries with hemodynamically balanced pulmonary stenosis and a ventricular septal defect, as observed in the present case. Electronic supplementary material The online version of this article (10.1186/s13256-019-2145-1) contains supplementary material, which is available to authorized users.

Methylmercury is widely known to be a toxic substance in the human, especially a nervous system. However, it is difficult to accurately measure the amount of methylmercury in blood, and the form of methylmercury is variously presented. The purpose of study was to compare the total mercury and methylmercury measurements techniques and detection levels between analytical institutions in two countries using the same elderly human blood samples. Total mercury using gold amalgamation direct mercury analysis method (both) and methylmercury using the dithizone extraction and gas chromatography-electron capture detector (GC-ECD) method (N Lab in Japan) and the cold vapor atomic fluorescence spectrophotometer (CVAFS) method (D Lab in Korea) were measured in 47 subjects who agreed to participate in this study. Total mercury concentrations in both analytical laboratories were observed at similar levels (9.4 versus 9.5 ug/kg, p=0.898) and the distribution was highly correlated. However, the concentration of methylmercury showed some difference between two laboratories (9.1 versus 8.6 ug/kg, p

Background Although ganglionated plexi (GPs) are important in the pathogenesis of arrhythmia, their patterns of atrial innervation have remained unclear. We investigated patterns of GP innervation to cardiac atria and the neuroanatomical interconnections among GPs in an animal model. Methods Atrial innervation by GPs was evaluated in 10 mongrel dogs using a retrograde neuronal tracer (cholera toxin subunit B [CTB] conjugated with fluorescent dyes). In Experiment 1, CTB was injected into the atria. In Experiment 2, CTB was injected into the major GP, including the anterior right GP (ARGP), inferior right GP (IRGP), superior left GP (SLGP), and ligament of Marshall (LOM). After 7 days, the GPs were examined for the presence of tracer-positive neurons. Results GPs in either right or left-side were innervating to both the same and opposite sides of the atrium. In quantitative analysis, right-sided GPs, especially ARGP, showed numerical predominance in atrial innervation. Based on the proportion of CTB-labeled ganglion in each GP, atrial innervation by GPs showed a tendency of laterality. In Experiment 2, CTB that was injected to a particular GP widely distributed in different GP. ARGP projected the largest number of innervating neurons to the IRGP, SLGP and LOM. Conclusion This study demonstrated that GPs project axons widely to both the same and opposite sides of atria. ARGP played a dominant role in atrial innervation. Furthermore, there were numerous neuroanatomical interconnections among GPs. These findings about neuronal innervation and interconnections of GPs could offer useful information for understanding intrinsic cardiac nervous system neuroanatomy.

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents.

The existence of myofibroblasts (MFBs) and the role of subendocardial smooth muscle (SSM) layer of human atrial tissue in atrial fibrillation (AF) have not yet been elucidated. We hypothesized that the SSM layer and MFB play some roles in atrial structural remodeling and maintenance of valvular AF in patients who undergo cardiac surgery.We analyzed immunohistochemical staining of left atrial (LA) appendage tissues taken from 17 patients with AF and 15 patients remaining in sinus rhythm (SR) who underwent cardiac surgery (male 50.0%, 54.1 ± 14.2 years old, valve surgery 87.5%). SSM was quantified by α-smooth muscle actin (α-SMA) stain excluding vascular structure. MFB was defined as α-SMA+ cells with disorganized Connexin 43-positive gap junctions in Sirius red-positive fibrotic area.The SSM layer of atrium was significantly thicker in patients with AF than in those with SR (P=.0091). Patients with SSM layer ≥ 14 μm had a larger LA size (P=.0006) and greater fibrotic area (P=.0094) than those patients whose SSM layer14 μm. MFBs were found in 7 of 17 (41.2%) patients with AF and 2 of 15 (13.3%) in SR group (P=.0456) in SSM area, colocalized with Periodic Acid-Schiff (PAS) stain-positive glycogen storage cells (95.5%).SSM layer was closely related to the existence of AF, degrees of atrial remodeling, and fibrosis in patients who underwent open heart surgery. We found that MFB does exist in SSM layer of human atrial tissue co-localized with PAS-positive cells.

This study attempted to calculate and investigate the incidence of hospitalized acute myocardial infarction (AMI) and stroke in Korea. Using the National Health Insurance claim data, we investigated patients whose main diagnostic codes included AMI or stroke during 2006 to 2010. As a result, we found out that the number of AMI hospitalized patients had decreased since 2006 and amounted to 15,893 in 2010; and that the number of those with stroke had decreased since 2006 and amounted to 73,501 in 2010. The age-standardized incidence rate of hospitalized AMI, after adjustment for readmission, was 41.6 cases per 100,000-population in 2006, and had decreased to 29.4 cases in 2010 (for trend P < 0.001). In the case of stroke was estimated at 172.8 cases per 100,000-population in 2006, and had decreased to 135.1 cases in 2010 (for trend P < 0.001). In conclusion, the age-standardized incidence rates of both hospitalized AMI and stroke in Korea had decreased continuously during 2006 to 2010. We consider this decreasing trend due to the active use of pharmaceuticals, early vascular intervention, and the national cardio-cerebrovascular disease care project as the primary and secondary prevention efforts.

ObjectiveWe evaluated the efficacy of minimally manipulative surgical strategies to harvest the saphenous vein for use in a Y-composite graft based on the left internal thoracic artery in terms of preservation of endothelial structure and function.MethodsTwenty patients who underwent off-pump coronary revascularization using the saphenous vein in a Y-composite graft based on the left internal thoracic artery were studied. The saphenous vein was harvested from each patient with minimal manipulation. An excess saphenous vein segment was removed before dilatation (control group), and a second segment was removed after dilation performed using a pressure-sensing syringe (conventional group). A third segment was obtained from a Y-composite vein graft dilated by flow and pressure from the left internal thoracic artery (composite group). Hematoxylin–eosin staining and immunohistochemistry using antibodies against CD31, CD34, von Willebrand factor, and endothelial nitric oxide synthase were performed. A generalized estimating equation was adopted for statistical analysis.ResultsHistologic and immunohistochemical studies revealed better endothelial preservation in the composite and control groups than in the conventional group (P

Aims Additional linear ablation lesions are created to improve the outcomes of pulmonary vein (PV) isolation during atrial fibrillation (AF) ablation. We aimed to evaluate the safety and feasibility of additional ablation sites in terms of anatomical characteristics. Methods and results Multi-detector computed tomography (MDCT) data from 140 consecutive patients (40 with AF, 84 males, 59 ± 11 years old) and additional 10 heart specimens were analysed for their anatomical characteristics at three types of mitral isthmus lines: anteromedial (AM), anterolateral (AL), and posterolateral (PL) lines (from right superior, left superior, and left inferior PV to 10, 12, and 4 o'clock position of the mitral annulus, respectively). The data demonstrated that the length was shortest at the PL lines (MDCT, 36.4 ± 8.6 mm; specimens, 31 ± 6 mm) and the maximal myocardial thickness was greatest at the AL lines (MDCT, 3.2 ± 1.0 mm; specimens, 5.0 ± 0.9 mm). Ridge, cord-like structure, or diverticulum was found most frequently at the AM lines (MDCT, 20%; specimens, 20%). Sinus nodal artery (SNA) was found near the AM (MDCT, 100%; specimens, 90%) and AL lines (MDCT, 46.3%; specimens, 30%), while left coronary artery (LCA) and cardiac vein were closest to the PL lines. The trend of these findings was not significantly altered with the presence of AF. Conclusions The PL lines were shortest among the three mitral isthmus lines, but closest to LCA. Myocardium was thickest at the AL line, and SNAs were frequently found on the anterior lines. Multi-detector computed tomography provided detailed information, and further studies are required to clarify the clinical impact of these findings.

BACKGROUND AND PURPOSE: We reported the MR findings of spinal metastatic lesions after SRS according to the volumetric changes (in press). However, in the case of osteoblastic metastatic lesions, tumor volume usually doesn9t change during remission. In this study, we retrospectively analyzed pre- and post-SRS CT and MR imaging findings of locally controlled osteoblastic spinal metastatic lesions besides volumetric changes MATERIALS AND METHODS: Among 113 spinal metastatic lesions in 72 patients, 10 lesions were osteoblastic. CT and MR images were reviewed to identify 4 parameters: 1) changes in tumor volume, 2) changes in CT attenuation, 3) changes in T2 signal intensities and 4) changes in degrees of contrast enhancement. RESULTS: Tumor volume was unchanged in 9 lesions and increased in 1 lesion. CT attenuation increased in 7 lesions and T2 signal intensities were heterogenous with dark signal foci within the tumor in 3 of 7 lesions and with dark and bright signal foci within the tumor in 4 of 7 lesions. In 3 lesions where CT attenuation decreased, T2 signal intensity became heterogenous with dark and bright foci in 2 of 3 lesions and T2 signal intensity became normalized in 1 lesion. The degree of contrast enhancement decreased in 8 lesions but 2 lesions showed persistent contrast enhancement. CONCLUSIONS: Further progression of sclerotic changes was a more common finding than loss of sclerotic foci. Main MR imaging features of osteoblastic lesions after treatment were development of dark with or without bright signal foci, with decrease in contrast enhancement.

Structured abstract Objectives The "lower versus upper leg saphenous vein (SV) composite graft based on the left internal thoracic artery (ITA) for coronary artery bypass grafting" trial was designed to compare the histologic, immunohistochemical and angiographic findings of lower versus upper leg SV composite grafts. Methods Twenty-six patients with multi-vessel coronary artery disease were prospectively randomized to undergo revascularization using a lower leg (group LLV, n =13) or upper leg (group ULV, n =13) SV composite graft based on the in situ left ITA. The SV was harvested with a "no-touch" technique, and two excess segments were removed from the distal and proximal portions of each SV conduit. Another proximal segment was removed from the reversed SV composite graft, which had been dilated by the native ITA pressure. Hematoxylin-eosin staining, immunohistochemistry, and early and 1-year postoperative angiographic results were compared. Results The histologic study showed that the proximal and dilated proximal SV conduit lumen diameters were smaller in group LLV than in group ULV (proximal, 623±143 μm vs. 858±266 μm, P =0.008; dilated proximal, 1138±419 μm vs. 1477±353 μm, P =0.047). However, there were no differences in the lumen diameters of the distal SV segments in terms of immunohistochemical comparisons, diameters, patency rates, or filling frame counts of the SV conduits on early and 1-year postoperative angiograms between the two groups. Conclusions Although the proximal segment luminal diameters were smaller in the lower leg SV, there were no differences in the immunohistochemical results or patency rates on early and 1-year postoperative angiograms between the lower and upper leg "no-touch" SV conduits.

Introduction Activation of MET, either by increased gene copy number (GCN) or mutation, has been detected in various cancers. We investigate the clinicopathologic features of MET gene copy in nonsmall cell lung cancer (NSCLC). Methods Tumor tissues were obtained from 180 resected NSCLCs, including 97 squamous cell carcinomas (SCCs) and 72 adenocarcinomas. No patient received epidermal growth factor receptor (EGFR)-targeted therapy. EGFR and MET GCNs were studied using fluorescence in situ hybridization (FISH) and were estimated according to the University of Colorado Cancer Center (UCCC) criteria. For MET , we also assessed GCNs using the Cappuzzo system. Results FISH-positive MET was observed in 16.7% using the UCCC criteria; specifically, amplification was seen in 3.9% and high polysomy in 12.8%. FISH-positive MET status was significantly correlated with FISH-positive EGFR ( p = 0.003). In the Cappuzzo system, high MET GCN (mean, ≥5 copies/cell) was found in 6.7% and also associated with FISH-positive EGFR ( p = 0.031). MET gene copy status was not associated with gender, smoking history, histology, or stage. However, true MET amplification was more frequent in patients with SCC than in those with adenocarcinoma. FISH-positive MET status predicted worse survival in patients with NSCLC at advanced stages ( p = 0.034) and in patients with SCC ( p = 0.028). In multivariate analyses, increased MET GCN was significantly associated with shorter survival in patients with SCC, as analyzed using both the UCCC and Cappuzzo criteria ( p = 0.019 and 0.008). Conclusions Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.

We report a case of bilateral pulmonary agenesis (BPA), which was suspected during a prenatal US examination and diagnosed by fetal magnetic resonance imaging (MRI). BPA is an extremely rare congenital anomaly and, although many fetal structural defects can be detected with a high degree of confidence after introducing high-resolution US, the prenatal diagnosis of BPA remains problematic. Other thoracic abnormalities, such as a congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, and pulmonary sequestration, should be excluded from the list of possible diagnoses before coming to the conclusion of BPA, because BPA is absolutely incompatible with extrauterine life, and an accurate internal diagnosis can prevent a futile intervention from being performed.

This study reports an autopsy case of a 53 year-old male with rapidly progressive extra-nodal NK/T-cell lymphoma accompanied with unusual clinical and pathologic features. He was initially presented with localized swelling and tenderness in the right lower extremity and the biopsy from the calf muscle was interpreted as granulomatous myositis masquerizing lymphoma. The biopsy from erythematous skin lesion of trunk showed infiltration of medium sized atypical lymphoid cells with relatively plump cytoplasm and immunophenotype of CD30+, CD56+/- and surface CD3-, which lead to the diagnosis of CD30+ anaplastic large cell lymphoma. About 2 months later, nasal obstruction was developed and the nasal biopsy was done. After confirmation of EBV infection, he was finally diagnosed as extra-nodal NK/T-cell lymphoma with peculiar immunophenotype of CD3 dim+ and CD30+. Despite the chemotherapy, he was going rapidly downhill and died of respiratory and multi-organ failure 8 months after the onset of soft tissue lesion. At autopsy, disseminated angiocentric lymphoma was found all over the internal organs including the brain. This case emphasizes that extra-nodal NK/T-cell lymphoma should be considered as a cause of granulomatous myositis and can express CD30 positivity and CD3 weak positivity, which are unusual but rarely predominant feature of NK/T-cell lymphoma.

Introduction: the cause of thromboangiitis obliterans (TAO) still remains unknown. We have reported that immunologic injury associated with T lymphocytes infiltration might be the initial etiologic mechanism in TAO. The present study was undertaken to examine further the mechanism of immune injury. Methods: arterial walls affected by TAO were obtained from eight patients with eight non-pulsatile arteries and one patent artery. Immunohistochemical and TUNEL studies were performed for phenotyping of the infiltrating cells with CD4 (helper T cell), CD8 (cytotoxic T cell), CD56 (natural killer cell), and CD68 (macrophage), for identification of cell activation with VCAM-1 and i -NOS, for the presence of cell death with TUNEL analysis, and for inflammatory cytokine detection with RT-PCR. Results: the characteristic features were luminal obliteration, together with a varying degree of recanalization. T cells infiltrated mainly in thrombus, intima, and adventita. Among infiltrating cells, CD4 T cells greatly outnumbered CD8 cells. VCAM-1 and i -NOS were expressed in endothelial cells around the intima (patent segment) or vaso vasorum (occluded segment). Endothelial cells in vaso vasorum stained positive with TUNEL. Interferon-γ mRNA was detected in two specimens. Conclusions: our results suggest that T cell mediated immune inflammation is a significant event in the development of TAO. Eur J Vasc Endovasc Surg 25 , 451-457 (2003)

Background/Aims Atrial anatomy and thickness may affect the electrical wave-dynamics of atrial fibrillation (AF). We explored the relationship between left atrial (LA) wall thickness (LAWT) or LA geometry and AF wave-dynamics. Methods We included 15 patients with persistent AF (age, 62.3 ± 11.9 years) who underwent AF catheter ablation. We measured the LAWT, LA endocardial curvature, and SD-curvature (surface bumpiness) from preprocedural computed tomography images. We compared those anatomical characteristics with electrophysiologic parameters such as dominant frequency (DF), Shannon entropy (ShEn), or complex fractionated atrial electrogram (CFAE)-cycle length (CL), calculated from intracardiac bipolar electrograms (300–500 points, 5 s), acquired during ablation procedures. Results 1. LAWT (excluding fat) varied widely among patients, locations, and types of AF. LAWT was inversely correlated with LA volume (r = -0.565, p = 0.028) and positively correlated with SD-curvature (r = 0.272, p < 0.001). 2. LAWT was positively correlated with ShEn (r = 0.233, p < 0.001) and negatively correlated with CFAE-CL (r = -0.107, p = 0.038). 3. In the multivariate linear regression analyses for AF wave-dynamics parameters, DF (β = -0.29 [95% CI -0.44–-0.14], p < 0.001), ShEn (β = 0.19 [95% CI 0.12–0.25], p < 0.001), and CFAE-CL (β = 7.49 [95% CI 0.65–14.34], p = 0.032) were independently associated with LAWT. Conclusion Regional LAWT is associated with LA structural features, and has significant correlations with the wave-dynamics parameters associated with electrical wavebreaks or rotors in patients with persistent AF.

The INO80 chromatin-remodelling complex has been implicated in DNA replication during stress in yeast. However, its role in normal DNA replication and its underlying mechanisms remain unclear. Here, we show that INO80 binds to replication forks and promotes fork progression in human cells under unperturbed, normal conditions. We find that Ino80, which encodes the catalytic ATPase of INO80, is essential for mouse embryonic DNA replication and development. Ino80 is recruited to replication forks through interaction with ubiquitinated H2A--aided by BRCA1-associated protein-1 (BAP1), a tumour suppressor and nuclear de-ubiquitinating enzyme that also functions to stabilize Ino80. Importantly, Ino80 is downregulated in BAP1-defective cancer cells due to the lack of an Ino80 stabilization mechanism via BAP1. Our results establish a role for INO80 in normal DNA replication and uncover a mechanism by which this remodeler is targeted to replication forks, suggesting a molecular basis for the tumour-suppressing function of BAP1.

This study was performed to assess the recent trends in lead, mercury, and cadmium levels in the blood among Korean adult population. The geometric means and 95 % confidence intervals (CIs) of blood lead, mercury, and cadmium concentrations were calculated using the data of the subjects from the third (2005, n = 1997), fourth (2008, n = 2005; 2009, n = 1991), and fifth (2010, n = 1989; 2011, n = 2014) Korea National Health and Nutrition Examination Survey. Blood lead levels in 2005, 2008, 2009, 2010, and 2011 declined to 2.61 μg/dL (2.51-2.71), 2.32 μg/dL (2.27-2.37), 2.29 μg/dL (2.23-2.35), 2.09 μg/dL (2.04-2.13), and 1.99 μg/dL (1.94-2.05), respectively. Blood mercury levels were 4.19 μg/L (3.99-4.39), 4.73 μg/L (4.57-4.89), 4.25 μg/L (4.09-4.41), 3.64 μg/L (3.49-3.80), and 3.08 μg/L (2.95-3.22), respectively, which indicated an increase in 2008 compared with those in 2005, and a clear downward trend from 2008 to 2011. Blood cadmium levels were 1.52 μg/L (1.47-1.57), 0.93 μg/L (0.89-0.97), 0.94 μg/L (0.90-0.98), 0.89 μg/L (0.87-0.92), 0.86 μg/L (0.83-0.89), respectively, which indicated very high levels in 2005, but a downward trend since 2008. Although the lead, mercury, and cadmium levels in the blood of the Korean adult population are on the decline, they are still relatively high compared with those for the population of the USA, Canada, and Germany. Thus, continuous biological monitoring and measures to reduce these levels are needed in Korea.

To determine the ventricular looping pattern in relation to cardiac laterality, we studied rat embryos treated with retinoic acid (RA). A total of 243 Wistar rat embryos from an in vivo treated group (a single dose of 20-40 mg/kg all-trans RA administered to pregnant rats on day 6.5 to 9.5) and 29 control embryos were examined on day 13 of gestation. Twenty-nine embryos from the in-vitro treated group (treated by all-trans RA at 2 x 10(-7) M for 6 hr on day 9.0 or 9.5 during the entire embryo culture for 72 hr) and seven control embryos were examined on day 12 of gestation. Abnormalities in cardiac laterality and ventricular looping were found in the in-vivo groups treated on day 8.5 and 8.75 and in the in-vitro group on day 9.0. Among 25 animals with abnormal laterality, right isomerism was the most common feature (22 cases), while the type of ventricular looping varied. Cases with normal laterality had a low incidence of abnormal looping (1.4%). In rat embryos treated with all-trans RA, normal cardiac looping was expected when cardiac laterality was normal. But in cases with abnormal laterality, the type of abnormal ventricular looping was unexpected.

OBJECTIVE: The objective of our study was to analyze MR images of vascular leiomyoma of the extremity and to compare these images with histopathologic findings to determine if a correlation exists. CONCLUSION: T2-weighted MR images of vascular leiomyoma of an extremity showed a mass with mixed areas that were both hyper- and isointense to skeletal muscle and also revealed a hypointense rim; these images correlate with histopathologic findings of smooth muscle, vessels, fibrous tissue, an intravascular thrombus, and a fibrous capsule.

Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital cardiac anomaly that has been classified into two types: one is a more frequent type having dysplasia of tricuspid valve (TV) with a small annulus, underdeveloped right ventricle (RV) with a hypoplastic cavity and a hypertrophic wall; the other type has severe dysplasia of TV and dilatation of RV, right atrium (RA), and right atrioventricular junction with thinning of the RV wall. We performed a morphologic study on 11 autopsied hearts with PAIVS, giving particular emphasis to the variation of morphology of the TV. We could classify these hearts into 3 groups according to the degree of right ventricular development. In the first group of 7 cases (type I), the RVs were underdeveloped. Thick leaflets, restricted valve apparatus with short chordae, and small annuli were characteristics of the TV. In the second group of 3 cases (type II), the RVs showed marked enlargement of the cavity and thinning of the wall. The TV showed redundant, dysplastic, sail-like anterior leaflets, and the downward displacement of septal leaflet and/or posterior leaflet, which are the findings frequently observed in Ebstein's malformation. The RVs were dilated and with partially unguarded tricuspid orifice. The septal leaflet of the TV was dysplastic and, in two cases, the septal leaflet showed chordal structure at the upper surface facing the RA, which is a peculiar finding that has not been described in the literature. The remaining case was a heart with a moderately developed RV (type III). The TV showed mildly dysplastic appearance and we classify this as a separate type, because we could expect the best surgical results in this type. This type had optimal size of RV and the mildest degree of dysplasia of TV. In PAIVS, the morphology of TV correlates well with the type of the right ventricular development.

Summary Background There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. Objective This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histologicai abnormalities in asthmatics according to the severity ot asthma. Methods Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and eosinophils in BALF were significantly increased in asthmatics and showed significant correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inllammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultra-structural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickeness of basal lamina. Conclusion These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.

We have experienced 7 cases of giant lymph node hyperplasia in the chest from 1981 to 1992. The ages of the 1 male and 6 female patients ranged from 9.9 to 40.4 years (mean age, 29.2 +/- 10.4 years). In 4 patients, a mass was discovered in routine radiographs. Focal calcification suggesting continual enlargement over a long time was noted in 1 patient. The sites of lesions were unusual in 2 patients (intercostal space and intrapulmonary fissure). All patients underwent surgical removal of the mass. Five cases had typical features of the hyaline-vascular type, and 2 cases revealed a mixture of the hyaline-vascular type and the plasma-cell type. Follow-up was available in all patients (mean follow-up, 31.9 months). In 1 patient, recurrence was observed 9 years after surgical removal. In general, giant lymph node hyperplasia can occur anywhere in the chest, grow without symptoms, and recur in spite of complete resection. Surgical resection and close follow-up are advised.

MicroRNA (miRNA) has a critical effect on tumorigenesis through post-transcriptional modification and is considered to be potential biomarkers for cancer diagnosis and treatment monitoring. We evaluated the expression pattern of three selected miRNAs (miR-21, miR-155, and let-7a) to evaluate their potential roles by quantitative reverse transcription-polymerase chain reaction using formalin-fixed and paraffin-embedded tissues of 63 surgically resected pulmonary neuroendocrine (NE) tumors (19 typical carcinoids (TCs), 6 atypical carcinoids (ACs), 19 large cell NE carcinomas (LCNECs), and 19 small cell lung carcinomas (SCLCs). Control amplification for U6 small nuclear RNA (U6) was performed in all samples. Normalized Ct values were calculated (Ct(Experimental miRNA) -Ct(U6) ) for each case and recorded. The expression levels of miR-21 and miR-155 were significantly higher in high-grade NE carcinomas (LCNECs and SCLCs) than in carcinoid tumors (TCs and ACs) (each P0.001). The expression level of miR-21 in carcinoid tumors with lymph node metastasis was significantly higher than in carcinoid tumors without lymph node metastasis (P= 0.010). To the best of our knowledge, the present study is the first to examine the expression patterns of miR-21 and miR-155 as an adjunctive diagnostic tool or clinically relevant biomarkers for pulmonary NE tumors.

Background— We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). Methods and Results— MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P P P =0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling–positive cells was 2-fold greater in the MR compared with the MR+sildenafil group. Conclusions— Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.

An echocardiographic study was performed on seven patients with twisted atrioventricular connections (criss-cross heart) relative to the usual atrial arrangement. The atrioventricular connections were concordant in five patients and discordant in two. The ventriculoarterial junction was either doubleoutlet right ventricle (n = 6) or discordant connections (n = 1). Associated cardiac defects were ventricular septal defect (n = 7), pulmonary stenosis (n = 5), straddling tricuspid valve (n = 2), and straddling mitral valve (n = 1). Malalignment between the atrial and ventricular septum was the most important feature of this disease and resulted in altered spatial orientation of the trabecular ventricular septum, and recesses in the ventricles and the right atrium. When assessed by echocardiography, these anatomical features were not invariably recognized in every case, but they were dependent upon the type of atrioventricular connections and the presence of straddling of the atrioventricular valves. Left ventricular recess was the most consistent feature and was present in every patient, regardless of the atrioventricular connections. Right atrial recess was found in four of five patients with concordant atrioventricular connections but was not present in patients with discordant atrioventricular connections. Right ventricular recess was recognized as such in a single patient with concordant atrioventricular connection and straddling mitral valve. The trabecular septum was oriented in a horizontal plane in hearts with concordant atrioventricular connections and without atrioventricular valve straddling. The trabecular septum was oriented semivertically in all other hearts. Echocardiography is a reliable diagnostic tool, not only for making a diagnosis of twisted atrioventricular connections but also for identifying altered orientation of the ventricular septum and abnormal recesses in the left ventricle and the right atrium.

The "crisscross" heart and the heart with "superoinferior ventricles" are closely related congenital cardiac malformations that are characterized by twisted atrioventricular connections. The authors studied the morphologic characteristics of three hearts with twisted atrioventricular connections as seen on magnetic resonance (MR) images. The most important clue to the diagnosis was the distorted atrioventricular connections that were demonstrated on serial images. The axes of the atrioventricular connections through the atrioventricular valves were not parallel to each other. The presence of unusual recesses in the cardiac chambers, the angulated or curved configuration of the atrial and ventricular septa, and the unexpected great arterial relationship for the given combination of segmental connections supported the findings of twisted atrioventricular connections. MR imaging facilitated the precise morphologic diagnosis of these hearts.

To apply the Osteoarthritis Research Society International (OARSI) assessment system to an osteoarthritis model, 44 Wistar rats were randomized into treadmill-running exercise or control group. At 6, 8, and 10 weeks, medial knee joints were histopathologically evaluated, and aggrecan neoepitope and TUNEL staining were performed. Cartilage changes in exercise group were histopathologically and histochemically compatible with early OA. Total modified Mankin system (MMS) scores were significantly higher at all time points (each P ≤ 0.01) in exercise than in control group. However, only tibial OARSI scores of runners were higher at 10 weeks (P

Diffuse panbronchiolitis (DPB), which is prevalent in Japan, is known to be rare outside Japan. Although a case of diffuse panbronchiolitis in a second generation Korean was reported in Japan in 1986, no case has been reported in Korea. Recently we found 5 cases of diffuse panbronchiolitis in Korea, two histologically proven and three clinically and radiologically suspected. All 5 cases had the typical respiratory symptoms and signs and a history of chronic sinusitis. In three clinically and radiologically suspected cases, high resolution computed tomography showed the typical findings of DPB and other diseases such as pulmonary emphysema, bronchial asthma, chronic bronchitis and bronchiectasis could be ruled out. More cases of DPB are expected to be found in Korea in the near future.(Internal Medicine 31 : 695-701, 1992)

Fluorescence in situ hybridization (FISH) has been known to be the most representative and standardized test for assessing gene amplification. However, FISH requires a fluorescence microscope, the signals are labile and rapidly fade over time. Recently, chromogenic in situ hybridization (CISH) has emerged as a potential alternative to FISH. The aim of this study is to test the reliability of CISH technique for the detection of epidermal growth factor receptor (EGFR) gene amplification in non-small-cell lung carcinomas (NSCLC), to compare CISH results with FISH. A total of 277 formalin-fixed and paraffin embedded NSCLC tissue samples were retrieved from the surgical pathology archives at Seoul National University Bundang Hospital. CISH and FISH examinations were performed to test EGFR gene amplification status. There was high concordance in the assessment of EGFR gene copy number between CISH and FISH tests (Kappa coefficient = 0.83). Excellent concordance was shown between two observers on the interpretation of the CISH results (Kappa coefficient = 0.90). In conclusion, CISH result is highly reproducible, accurate and practical method to determine EGFR gene amplification in NSCLC. In addition, CISH allows a concurrent analysis of histological features of the tumors and gene copy numbers.

Mucous gland adenoma of the bronchus is a truly benign, well defined, intraluminal mass that manifests on CT with air-meniscus sign or abutting the bronchus. We report the CT findings of mucous gland adenoma in two patients.

Summary Background Recently, the demand for intraoperative pathology consultation for small pulmonary nodules including ground-glass opacity (GGO) has been increasing. Evaluation of minute precancerous lesions of the lung by frozen section is very difficult for the pathologist as uninflated lung tissue usually shows severe atelectasis and frozen artifact. We tried to inflate lung tissue with the embedding medium used for frozen section and to determine the appropriate dilution ratio of the embedding medium for optimization of frozen section morphology. Methods The lung specimens were derived from 10 patients who underwent video-assisted thoracoscopic surgery (VATS) due to pneumothorax (four patients) and GGO (six patients) detected on high-resolution computed tomography (HRCT) at Seoul National University Bundang Hospital. The pneumothorax specimens were divided into six groups—uninflated, inflated with saline, and inflated with embedding medium (not diluted, 1:1, 2:1 and 2:3). The qualities of the frozen sections were compared with corresponding permanent paraffin sections. Lung specimens obtained from the six people with GGO detected on HRCT were submitted for intraoperative pathology consultation. Frozen sections were made after inflation with optimally diluted embedding medium determined by the above experiment with pneumothorax specimens, and the frozen section diagnoses (FSD) were compared with the final pathologic diagnoses of corresponding permanent paraffin sections. Results The frozen section quality of lung tissue was excellent after simple inflation with diluted embedding medium (2:3). Minute precancerous foci such as atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC) could be readily identified in frozen sections using this method. Of the six patients with solitary GGO, four were diagnosed as BAC, nonmucinous type and two were as AAH on the frozen sections. Intraoperative FSD corresponded well with final diagnoses obtained with paraffin sections. Conclusions An inflation procedure using diluted embedding medium can make lung tissue expand well during frozen section. Minute and even nonpalpable GGO lesions could be detected more easily by this technique in frozen sections, which would be helpful in determining how extensive a surgical procedure needs to be. Application of this procedure appears to improve the accuracy of FSD of minute precancerous pulmonary nodules.

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent. Graphical Abstract

Castleman's disease represents an atypical lymphoproliferative disorder, infrequently associated with various immunologic abnormalities or subsequent development of malignancy such as Kaposi sarcoma, malignant lymphoma and plasmacytoma. Its clinicopathologic features depend on various etiologic factors such as Kaposi sarcoma herpesvirus (KSHV), oversecretion of IL-6, adhesion molecule and follicular dendritic cell dysplasia, etc. To investigate the relationship of Castleman's disease (CD) and the above factors, we reviewed 22 cases of CD. Four cases of KSHV positive CD were detected, all multicentric, plasma cell type, and these cases displayed prominent vascular proliferation, characteristic 'Kaposi-like lesion'. IL-6 and CD54 positive mononuclear cells were scattered in interfollicular areas of KSHV positive cases. Follicular dendritic cell hyperplasia, vascular proliferation, expression of IL-6 and CD54 did not show any significant difference between solitary vs multicentric type, and plasma cell type vs hyaline vascular type. Our study suggests that KSHV positive CD reveals unique pathologic features, and the probable relationship of KSHV and IL-6 and CD54 is discussed.

BackgroundThe morphological definition of atrial chambers, and the determination of atrial laterality, are based on analysis of the structure of the atrial appendages. The systemic and pulmonary venous connections to the heart, nonetheless, are important in the management of patients having isomeric appendages. In this study, therefore, we analysed the morphology of the postero-superior walls of the atrial chambers so as to provide evidence concerning the morphogenetic background of those hearts, and to improve operative management.MethodsWe reviewed 15 autopsied specimens with isomeric right appendages, and 10 with isomeric left appendages, paying particular attention to the morphology of the systemic and pulmonary venous connections. The postero-superior walls of the atrial chambers can be made up of the atrial body, the systemic venous components, or the pulmonary venous component. We analysed the contributions made by each of these components.ResultsThe postero-superior walls of the atrial chambers were markedly variable, but could be grouped into five patterns. Bilaterally well-developed systemic venous components and absence of the pulmonary venous component within the hypoplastic atrial body were present in 9 hearts with extracardiac pulmonary venous connections in the setting of right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the hypoplastic atrial body, were present in 5 hearts with intracardiac pulmonary venous connections in right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the sizable atrial body, were present in 1 heart with an intracardiac pulmonary venous connection in right isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of one systemic venous component, were present in 7 hearts with left isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of bilateral systemic venous components, were present in 3 hearts with left isomerism.ConclusionsThe postero-superior walls of the atrial chambers in hearts with isomeric atrial appendages can be analysed on the basis of a compound structure made of bilateral systemic venous components, a central pulmonary venous component, and the body of the atrium. Hearts with isomeric right appendages have absence or hypoplasia of the pulmonary venous component, while hearts with isomeric left appendages have hypoplastic systemic venous components.

Morphologic features and pathogenesis of arterial changes occurring in Buerger's disease (thromboangiitis obliterans) are still controversial. This study describes histopathologic features of medium sized arteries from patients with Buerger's disease, particularly of the internal elastic lamina in relation to the immunologic mechanism of the injury. Seventeen segments of occluded arteries (femoral or popliteal arteries) from 17 patients with Buerger's disease were analyzed by histopathological and immunohistochemical methods. The most characteristic features were total luminal obliteration, together with a varying degree of recanalization and deposition of hemosiderin pigments. Detailed analysis, however, showed marked undulation and multiplication of the internal elastic lamina (100%) associated with basophilic degeneration and delicate linear calcification (47%). Lymphocytic infiltration along the internal elastic lamina was seen in 71% and was associated with localized edema. Lymphocytes along the lamina were consistently positive for T cell marker. Mild to moderate fibrosis was present at the media in 24%. Adventitial changes included mild, nonspecific and irregular fibrosis seen in 53%. Immunologic injury to the internal elastic lamina associated with T-lymphocytic infiltration might be the initial morphogenetic mechanism of the thrombotic occlusion and organization of medium-sized arteries in Buerger's disease.

Thirty-six pairs of conjoined twins are reviewed from the joint experience of the authors. The external forms of conjunctions were 18 thoracopagus (joined at chest), eight cephalothoracopagus (joined at head and chest), eight dicephalus (single trunk and two heads), one craniopagus (joined at head), and one omphalopagus (joined at abdomen). There was one case with a single conventional heart in association with isomerism of the left lungs and absence of the heart in the left-side twin. Six cases had two conventional hearts. All of them had associated lesions, which were more severe in three cases (50%) with abnormal laterality. All of the cephalothoracopagus (eight cases) had two shared hearts. Cardiac lesions were commonly seen in the posterior heart, but the arrangement of atrial appendages were normal in every heart. Twenty-one cases of either dicephalus or thoracopagus had a compound heart. Three cases (14%) had fusion only at the level of venous sinus; three others (14%) were fused at the atrial level only, but 15 cases (71%) had fusion at both atrial and ventricular levels. Abnormal laterality was an associated lesion in ten cases (48%) with a compound heart. The fusion at the atrial level always occurred between right atriums, but ventricular fusion was more commonly between two left ventricles. Four atrial or ventricular chambers, if fused, were arranged in a cruciate arrangement. Mode of conjunction was as important, in the formation of the cardiovascular system, as was the degree of fusion. Abnormal laterality, which is commonly associated in lateral or mixed lateral/facing conjunction, was the most important factor affecting the general morphology of the cardiovascular system.

BACKGROUND In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies. METHODS AND RESULTS The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects. CONCLUSIONS Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins.

Background Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury. Methods Animals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue. Results The PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney. Conclusion These findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.

Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.

A 72 year old man with simultaneously occurring squamous cell and neuroendocrine carcinomas in association with cryptogenic fibrosing alveolitis is reported. The tumours were separate and both were in the fibrotic area of the right lower lobe.

We studied the biological effect of a magnetic field on murine brain and kidney. Magnetic field we used was generated by Magno-DR apparatus (Hanil Co., Korea) which produced a high density unipolar square pulsating magnetic field, about 0.3 approximately 0.5 Tesla at 7 Hertz. Animals were placed in the chamber of the machine for various times from 4 hours to 24 hours. Histological sections of brain and kidney were made after perfusion fixation with paraformaldehyde. The light microscopic examination showed eosinophilic change of cytoplasm and positive immunohistochemical reaction to amyloid precursor protein in the neurons of the cerebral cortex. However, the thalamus and brain stem were less affected. The changes in the brain was seen in the mouse exposed more than 12 hours. The renal tubular epithelium showed degenerated tubules scattered in cortical area but little change was noted in glomeruli in the cortex and collecting tubules in the medulla. Immunohistochemistry of the kidney showed weakly positive reaction for the amyloid precursor protein in the distal tubular epithelium after 4 hours of exposure. These data suggest that strong pulsating magnetic fields could induce deleterious effect on the murine brain tissue and renal cortical tubules.

The evaluation of prognostic factors in infants with critical stenosis of the aortic valve and intact ventricular septum is often misleading due to a complex interaction among lesions in the mitral and aortic valves, and the left ventricular myocardium. The clinical parameters on the left ventricular function, such as ejection fraction and left ventricular end-diastolic volume, are of particular interest as their effects on survival are very controversial. We performed a clinicopathologic analysis of two autopsied cases of this disease. Besides the morphological hallmarks of the aortic and mitral valves, these two cases showed two extreme types of pathology in the left ventricular myocardium, which might have significant impacts on the clinical evaluation of the left ventricular function. Case 1 showed endocardial fibroelastosis associated with abnormal intertrabecular spaces (so-called spongy myocardium), obscuring accurate estimation of the left ventricular end-diastolic volume. Case 2 showed ischemic necrosis of the apical part of the left ventricular myocardium. This infarct was associated with acute and chronic subendocardial ischemia and mild endocardial fibroelastosis. Aggravation of the left ventricular failure could be caused by the recent ischemic insult. The evaluation of the left ventricular function, therefore, should include the evaluation of the morphologic status of the myocardium as regards to whether there is ischemia, endocardial fibroelastosis or hypertrophied trabeculae in addition to stenotic lesions in the aortic and mitral valves.