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Digital-light-processing (DLP) three-dimensional (3D) bioprinting, which has a rapid printing speed and high precision, requires optimized biomaterial ink to ensure photocrosslinking for successful printing. However, optimization studies on DLP bioprinting have yet to sufficiently explore the measurement of light exposure energy and biomaterial ink absorbance controls to improve the printability. In this study, we synchronized the light wavelength of the projection base printer with the absorption wavelength of the biomaterial ink. In this paper, we provide a stepwise explanation of the challenges associated with unsynchronized absorption wavelengths and provide appropriate examples. In addition to biomaterial ink wavelength synchronization, we introduce photorheological measurements, which can provide optimized light exposure conditions. The photorheological measurements provide precise numerical data on light exposure time and, therefore, are an effective alternative to the expendable and inaccurate conventional measurement methods for light exposure energy. Using both photorheological measurements and bioink wavelength synchronization, we identified essential printability optimization conditions for DLP bioprinting that can be applied to various fields of biological sciences.

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.

Primary cardiac tumors are rare, with a prevalence of 0.001-0.2%. Among such tumors, cardiac hemangioendotheliomas are some of the most uncommon. In Korea, there have been no reports of hemangioendothelioma occurring in the heart of infants. We herein report a case of an infant that was admitted to our medical center and presented with cough and a runny nose. The initial diagnosis was acute bronchiolitis. Cardiomegaly was observed on chest radiography. Echocardiography revealed a tumor measuring 3.5×4.0 cm in the right atrium. The infant was transferred to a tertiary medical center for tumor excision. The excised lesion was 3.8×3×3.2 cm in size, and biopsy confirmed a diagnosis of hemangioendothelioma. In this case report, we describe our experience with a rare case involving cardiac tumor in an infant with an upper respiratory tract infection.

We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later. Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance. Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates. Extensive contraction band necrosis was observed in the atria and ventricles. There was no evidence of microthrombosis or infection in the heart and other organs. The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine., Graphical Abstract

Differential diagnosis of an intracardiac mass is difficult when detected only by echocardiography before a biopsy is completed. However, treatment cannot be postponed until the biopsy results are obtained. We report the case of a 12-year-old girl who presented with an intracardiac mass in the mitral valve mimicking infective endocarditis and severe mitral regurgitation. The mass was finally diagnosed as valvulitis associated with systemic juvenile idiopathic arthritis, which was complicated with macrophage activation syndrome. After careful exclusion of acute infectious disease, we started steroid pulse therapy and administered tocilizumab to treat the cytokine storm before performing the surgery. Finally, we performed mass excision and mitral valve replacement after immunosuppressant therapy.

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.

Background Atrial fibrillation (AF) in adult patients with atrial septal defect (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium (LA), which is the opposite situation in patients with AF and mitral valvular disease. This study was to compare the histopathological change in the atrium of patients with AF of two different etiologies: ASD and mitral disease. Methods Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group 2 included patients with ASD with AF (6), and Group 3 included patients with mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial tissues were obtained during surgical procedures and stained with periodic acid-Schiff, smooth muscle actin, Sirius red, and Masson’s trichrome to detect histopathologic changes compatible with AF. The severity of histopathological changes was represented with “positivity” and “strong positivity” after analyzing digitalized images of the staining. We investigated the relationship between the degree of atrial dilatation and severity of histopathological changes according to the groups and tissues. Results Group 2 and Group 3 patients showed a tendency toward an enlarged RA volume and enlarged LA volume, respectively, compared with each others. However, in the histopathologic analysis, “positivity” and “strong positivity” showed no significant positive correlations with the degree of atrial volume in special staining. Conclusions A similar degree of histopathologic changes was observed in both atria in patients with AF (Group 2 and 3) regardless of the degree of dilatation of atrial volume and disease entities.

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.

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 (CtExperimental miRNA-CtU6) 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 P < 0.001). 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.

A 22-year-old woman presented with ventricular tachycardia and heart failure of acute onset, and rapid hemodynamic deterioration despite medical treatment. The heart failure required extracorporeal membrane oxygenation followed by cardiac transplantation. The histopathological mapping of the ventricular conduction system of the explanted heart revealed focal fibrosis of the myocardium in close proximity to the left posterior fascicle. There was no other evidence of myocardial infarction or myocarditis. Immunohistochemical staining did not demonstrate any cause of this lesion; however, atrophy of cardiac muscle fibers around the lesion was noted. The focal fibrosis was presumed to be the cause of the ventricular tachycardia.

Background and aim: The objective of this paper is to evaluate the workload of staff in anatomic pathology (AP) laboratories in Korea. Methods: A survey was conducted at 197 AP laboratories in South Korea, these were categorized as 37 free standing laboratories, 14 laboratories in non-training hospitals (without residents), 79 in training hospitals (with residents), and 67 in university hospitals. The workloads of the staff were analyzed using the mean and standard deviation of the number of cases. Results: In total, there were 512 pathologists, 806 technicians and 205 cytopathology screeners. In a year, they processed a total of 3,150,261 histopathology cases and 4,115,420 cytopathology cases. The numbers of histopathology cases per pathologist or technician in one laboratory were 6,950 ± 6,748 and 4,074 ± 3,630, respectively. There were 109 laboratories that employed 205 cytoscreeners in addition to the 308 pathologists, where a cytoscreener read 14,780 ± 13,110 cases of cytopathology. However, in 88 laboratories, there were 132 pathologists who were not assisted by cytoscreeners, where a pathologist was reading 4,277 ± 3,033 cases of cytopathology. Conclusion: We propose a mean plus a standard deviation as a recommended guideline for staff workload at each laboratory setting to be used for a quality assurance program.

Background and aim: Determining the specific type of amyloid is critical as prognosis and treatment of amyloidosis completely differs according to the type. As aggressive and radical treatments for systemic amyloidosis are newly emerging, accurate typing of amyloid has become more important. Methods: Immunohistochemistry was performed with four antibodies to major amyloid proteins on tissue microarrays. Results: Overall, of 49 cases from 39 patients, 32 specimens (65%) were successfully classified by immunohistochemistry (IHC) with clinical information. Immunoglobulin light chain related (AL) amyloid was the most common type, accounting for 49% of all. Among 19 patients with AL amyloid, 7 (37%) had multiple myeloma, while serum amyloid A related (AA) amyloid was found in 8 (16%) specimens, and all patients had chronic inflammatory diseases. In 18 specimens (35%), however, the type of amyloid could not be established due to lack of clinical clue and/or inconclusive immunostaining. Particularly, antibodies to lambda light chain and transthyretin frequently stained amyloid of other origin additionally, therefore complicated the typing of amyloid. Conclusion: Immunohistochemistry could be applied as useful tools for classification of amyloidosis in most cases and should be carefully interpreted in the light of clinical information.

Sudden unexpected deaths due to cardiovascular diseases make up almost half of all natural deaths. Practical guidelines are needed for forensic autopsy practice in cases of natural unexpected deaths due to ischemic heart disease or other cardiovascular diseases in Korea. An evaluation of the clinical history is the first step, including the collection of all available information on the subject. As a standard autopsy procedure, every subsystem of the heart and vessels should be thoroughly studied including the coronary arteries, the myocardium, the cardiac valves, and the conducting system. In addition, histological, toxicological, biochemical and molecular analysis need to be applied to the detection of myocardial infarction from the medico-legal point of view. Also important is the assessment of risk factors for natural unexpected cardiac death (NUCD) in order to establish a cause–effect relationship. There are three groups of ischemic conditions of heart leading to NUCD, those being acute myocardial infarction, atherosclerotic heart disease and critical coronary atherosclerosis. Additionally, there are practical concerns on formulating the report. Pathologists may use sudden cardiac death or NUCD as a main diagnosis when there is no alternative diagnosis, though they would do better to comment on conditions contributing to the death. Finally, pathologists should be encouraged to suspect unexplained causes of death in order to find clearer answers.

Background and aims: The systemic effects associated with mechanical ventilation of lungs injured by hydrochloric acid (HCl) aspiration are unexplored. We hypothesize that low dose acid aspiration will predispose the lung and the kidney to damage from large tidal volumes through activation of inducible nitric oxide synthase (iNOS). Materials and methods: Hydrochloric acid (HCl; pH 1.25, 1 mL/kg), or an equal amount of 0.9% sodium chloride (NaCl), were inserted into the trachea of rats immediately prior to mechanical ventilation. Rats were then ventilated with room air at 85 breaths per minute for 2 hours, either with a tidal volume (VT) of 7 mL/kg or 14 mL/kg (VT7, VT14) and zero end expiratory pressure. Kidney microvascular leak, which was assessed by measuring urine protein over 24 hours and by Evans blue dye (EBD) technique, was used as an indicator of systemic microvascular leak. Results: A significant microvascular leak occurred in both lung and kidney exposed to VT14 with HCl compared to those exposed to either VT7 with HCl or the NaCl control group. iNOS activity was significantly increased in the lung and the kidney tissue in VT14 with acid aspiration. The relatively selective iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), attenuated the EBD microvascular leak in lung and kidney and the proteinuria in the VT14 with acid aspiration group. Conclusion: iNOS may have mediated the systemic microvascular leak in the present model.

Introduction The present study was designed to determine the in vivo patency and recellularization pattern of acellularized small-diameter xenogenic arterial grafts. We implanted acellularized porcine carotid arteries in bilateral carotid arteries of goats and microscopically analyzed the recellularization pattern of these grafts with the recipient's cells over time. Material and Methods Carotid arteries of pigs weighing 30–40 kg were harvested and decellularized with hypertonic saline followed by sodium dodecyl sulfate. Acellularized porcine carotid vascular xenografts (0.4–0.5 cm in diameter) were prepared into 4 cm-long segments and implanted bilaterally in the carotid arteries of 10 black-haired goats. The in vivo patency of the implanted acellularized xenogenic grafts was evaluated at regular intervals by color Doppler ultrasonography. The goats were sacrificed at predetermined intervals (1 week, 1 month, 3 months, 6 months, 12 months after implantation), two animals at each interval. Upon retrieval, visual inspections and histopathologic examinations of the grafts were performed. To identify smooth muscle cells and functioning endothelial cells, immunohistochemical staining for alpha-smooth muscle actin and von Willebrand factor were also performed. Results and Conclusions All experimental animals survived the observation period. Nineteen out of 20 implanted grafts showed patency with no thrombi. Microscopic analysis revealed that the grafts were completely covered with the hosts' endothelial cells, beginning from anastomotic sites. The grafts were gradually recellularized with recipients'cells including fibroblasts, myofibroblasts and smooth muscle cells. In conclusion, this study suggested that acellularized xenogenic vascular grafts can be a good alternative for the small-diameter vascular graft.

Glioblastoma (GBM) can be classified into molecular subgroups, on the basis of biomarker expression. Here, we classified our cohort of 163 adult GBMs into molecular subgroups according to the expression of proteins encoded by genes of alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase (IDH) and TP53. We focused on the survival rate of molecular subgroups, depending on each and various combination of these biomarkers. ATRX, IDH1 and p53 protein expression were evaluated immunohistochemically and Kaplan-Meier analysis were carried out in each group. A total of 15.3% of enrolled GBMs demonstrated loss of ATRX expression (ATRX-), 10.4% expressed an aberrant IDH1 R132H protein (IDH1+), and 48.4% exhibited p53 overexpression (p53+). Survival differences were statistically significant when single protein expression or different combinations of expression of these proteins were analyzed. In conclusion, in the case of single protein expression, the patients with each IDH1+, or ATRX-, or p53- GBMs showed better survival than patients with counterparts protein expressed GBMs. In the case of double protein pairs, the patients with ATRX-/p53-, ATRX-/IDH1+, and IDH1+/p53- GBMs revealed better survival than the patients with GBMs with the remained pairs. In the case of triple protein combinations, the patients with ATRX-/p53-/IDH+ showed statistically significant survival gain than the patients with remained combination of proteins-expression status. Therefore, these three biomarkers, individually and as a combination, can stratify GBMs into prognostically relevant subgroups and have strong prognostic values in adult GBMs.

Researchers have an ethical responsibility to report the results of research involving human subjects. Dissemination of results ensures that patient care is based on good science and that the field of medicine advances based on complete and accurate knowledge. However, current evidence suggests that publication is often neglected or substantially delayed, especially in the case of negative and inconclusive results. Researchers, editors and reviewers should value all high-quality research regardless of the conclusiveness of the results and ensure that all research involving human subjects is registered in a publicly accessible database.

BackgroundWe implanted frozen and acellularized porcine xenograft vessels as small-diameter arterial grafts in goats and comparatively analyzed the explanted grafts by gross observation and by light microscopy at predetermined periods.Materials and MethodsPorcine carotid arteries were harvested and immediately stored within a tissue preservation solution at −70°C in a freezer designated for frozen xenograft vessels. The acellularized xenograft vessels were prepared with NaCl-SDS solution and stored frozen until use. One pair of porcine xenograft vessels were used to compare the frozen and acellularized grafts in the bilateral carotid arteries in one goat. The grafts were implanted for one, 3, and 6 months in three animals. Periodic ultrasonographic examinations were performed during the observation period. Explanted grafts were analyzed by gross observation, and by light microscopy.ResultsAll animals survived the experimental procedure without specific problems. Ultrasonographic examinations showed excellent patency in all grafts during the observation period. Gross observations revealed nonthrombotic patent smooth lumens. Microscopic examinations of the explanted grafts showed satisfactory cellular reconstruction to the 6-month stage. Although more inflammatory responses were observed in the early phase of implantation of frozen xenografts than of acellularized xenografts, there was no evidence of significant rejection of the frozen xenografts.ConclusionThese findings suggest that porcine vessel xenografts, regardless of them being acellularized or simply frozen xenografts, can be acceptably implanted in goats as a form of small-diameter vascular graft.

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.

In January 2009, a new classification of pathology services was been launched for the reimbursement by the National Health Insurance system in Korea. Five basic types of surgical pathology services are reclassified into 13 types and their resource based relative value scores are adjusted. In this report, we summarize the history of the classification system for the reimbursement on pathology services and report the impact of the change in January 2009 on the distribution of cases and contribution on the income of the department of pathology from each class at the Seoul National University Hospital.

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.

There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We established a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma within a predictable time span. Using this animal model and a morphological approach, thymic epithelial tumour progression was studied with reference to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the entire spectrum from cortical type thymoma to thymic carcinoma. Thymic size tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiated thymic carcinoma. When SV40T TG mice (248 line) reached a certain age, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma-carcinoma sequence. When the mice were 9 weeks of age, the thymuses formed gross masses compatible with cortical thymoma. At 14 weeks of age, WDTC appeared against the background of cortical thymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullary thymomas did not develop in the mice, and no transition from medullary-type thymomas to thymic carcinomas was observed. In this SV40T transgenic mouse model, thymic carcinoma is clearly preceded by cortical-type thymoma. These transgenic mice may provide an interesting model for the progression from cortical thymoma to WDTC and/or high-grade carcinoma.

Each of the two minimally united livers of thoracopagus conjoined twins occupied an epigastrium on opposite aspects of the conjoined abdomen, straddling the plane of conjunction, instead of being located beneath the domes of the diaphragm. Whereas the hepatic artery and portal vein of the right twin supplied only the larger “anterior” liver, the same vessels in the left twin divided to provide blood for both the “anterior” and the “posterior” liver. Thus the “posterior” liver had only one porta hepatis while the “anterior” liver had two. In addition, the hepatic veins of both ectopic livers were found to drain into the inferior vena cava of only the left twin. All of these anomalies have been reported, albeit rarely, among 477 cases of thoracopagus and omphalopagus twins recently reviewed. A theory explaining the abnormal embryology of the liver is proposed.

A variety of experiments of endothelial cell seeding on artificial vessels have been performed. To improve endothelialization, one or two extracellular matrix components have been used as an underlying matrix. Although these methods have succeeded in in vitro experiments, they have not performed well in vivo. In this study, the authors used the whole extracellular matrix (ECM) excreted from fibroblasts as an underlying matrix. Fetal human fibroblasts were cultured on a polyurethane (PU) sheet. After confluence was attained, the cytoskeleton and the nuclei of the fibroblasts were destroyed using Triton-X, mitomycin, and irradiation. Omental microvascular endothelial cells from adult humans were seeded on various supports. After 12 days in culture, the cells were counted. The authors found that the ECM treated by irradiation had the highest cell number. In addition, the cells on this support exhibited the best morphologic appearance. Finally, the authors performed preliminary animal experiments. The PU vessels (inner diameter: 1.5 mm) treated with ECM were implanted in the arteries of rats. After the vessels had been implanted for 5 weeks, the authors found that the surface of the PU vessels were completely covered with endothelial cells. On the basis of these results, the authors conclude that the whole ECM makes a better underlying substrate for the endothelialization of small diameter artificial vessels.

A ventricular septal defect is, almost always, an integral part of double outlet right ventricle and has been classified into the subaortic, subpulmonary, doubly committed and non-committed varieties. This study was performed to correlate the cross-sectional imaging characteristics of such ventricular septal defect in double outlet right ventricles using pathological specimens. The extent and the orientation of the outlet septum were the most important in the differentiation of the four varieties of ventricular septal defect. In the subaortic variety, the outlet septum fused with the left anterior margin of the defect, this being marked by the anterior limb of the septomarginal trabeculation. In the subpulmonary variety, the outlet septum fused with the right posterior margin of the defect, this being the posterior limb of the septomarginal trabeculation. The outlet septum was vestigial in case with doubly committed defects. In those with non-committed defects, the defect was not shown in those images or sections which demonstrated the outlet septum.

Objective. The objective of this study was to present a case of trigger point injection-related pneumothorax treated by computed tomography (CT)-guided needle aspiration. Design. Case report. Setting. The study was set in a community hospital practice. Patient. The study consisted of a singlecase. Intervention. The intervention used for the study was CT-guided needle aspiration of the pneumothorax. Results. The result of the study was the successful evacuation of the pneumothorax and lung expansion. Conclusion. CT-guided needle aspiration is a viable management option for symptomatic patients with iatrogenic pneumothorax.

‘Putting Evidence-Based Practice into Action: EBP Journal Clubs’ was the theme of one of the workshops at the recent 10th International Congress on Medical Librarianship held in Brisbane, Australia. The workshop's focus was the role of librarians in providing a non-threatening environment that would encourage clinicians to make evidence-based practice (EBP) a core part …

SummaryThe arterial supply to the lungs in cases with tetralogy of Fallot with pulmonary atresia or critical pulmonary stenosis is mostly via the arterial duct or else by collateral arteries arising directly or indirectly from the aorta. Nine anatomical specimens with collateral arteries were studied by blunt dissection to determine the arterial supply to each pulmonary segment. The precise supply varied from case to case but, overall, nearly two-thirds of the pulmonary segments were connected to the central pulmonary arteries. A quarter were supplied exclusively by systemic-to-pulmonary collateral arteries, with the remainder having a dual supply. Coexistence of ductal connections and systemic-to-pulmonary collateral arteries was seen in one case. Anastomoses between vessels of different origins were observed up to the segmental level in eight of the nine cases. In four cases, the anastomoses formed arterial rings. The extent of pulmonary parenchyma supplied by arteries from different sources and the presence of arterial anastomoses in these malformations have implications on the planning of surgical repair.

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)

This study was performed to evaluate the clinical feasibility of use of immunologically nontreated xenogenic valves, using a porcine-to-goat pulmonary valved conduit implantation model. Porcine pulmonary valve conduits were prepared with no specific immunological treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were assigned at predetermined intervals (1 day, 1 week, and 3, 6, and 12 months) as two animals for each interval. Echocardiographic examinations of the valves were performed before sacrifice. Upon retrieving the xenograft specimens, they were inspected visually and microscopically. Ten of the 12 animals survived the predetermined observation periods. Variable degrees of pulmonary regurgitation were the main findings on echocardiographic evaluations. On gross examination of the explanted specimens, all leaflets, except in one animal that prematurely died, were fairly well preserved. They were slightly shortened but free of thrombosis or vegetation. Aneurysmal dilatations of the anterior wall of the implanted pulmonary artery were observed in one of 12-month-survival animals and in another one of 3-month-survival animals. Microscopically, the three components of implanted xenografts (the pulmonary artery, valve, and infundibulum) were shown to be gradually replaced with host cells in time, while maintaining structural integrity. The nuclei of the donor tissue disappeared through pyknosis and karyolysis. In conclusion, immnunologically untreated xenogenic pulmonary valved conduits can be an alternative potential as valve substitutes with distinctive advantages of providing self-healing potential, despite a few problems observed in the current study such as occurrences of pulmonary regurgitation and sporadic cases of aortic aneurysm.

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

An experiment to study the role of contact-activation leukocyte sequestration in the formation of ischaemia-reperfusion injury (I-R injury) was carried out. The study was conducted using light and electron microscopic analyses in an ovine cardiopulmonary bypass (CPB) model using a membrane oxygenator. Five adult sheep were used in the study. The CPB circuitry consisted of a roller pump and a membrane oxygenator. During CPB, flow rates ranged from 50 to 60 ml/kg/min with mild hypothermia. The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter, total CPB was performed for 100 min, followed by another 10 min of partial CPB. Lung biopsy specimens for light and electron microscopy were obtained from the upper lobe of the right lung before CPB, 109 min after the start of CPB (just before reperfusion) and 30 min after weaning (after reperfusion). A portion of the lung biopsy specimen was taken for a water content measurement at the same time intervals. For measuring the left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 and 109 min after the start of CPB, and 30 and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 and 120 min after weaning. Plasma malondialdehyde (MDA) was checked before thoracotomy, 109 min after the start of CPB and 30 min after weaning. On both light and electron microscopic examination, mild to moderate acute lung change was observed after ischaemia-reperfusion. Interstitial oedema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. However, few neutrophils were seen. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Neither significant differences in the transpulmonary gradients of leukocytes nor a significant complement activation, expressed by C3a levels, was observed. The MDA level did not display a significant change related to lung reperfusion despite an increase in MDA after the start of CPB. These findings indicate that I-R injury during CPB may not be from complement-activation leukocyte sequestration, but from another source of oxygen free radicals related to CPB.

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.

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.

SummaryAnatomic data are presented of a female abortus with the unusual combination of Ebstein's malformation and atrioventricular septal defect with right isomerism of the atrial appendages, left-hand ventricular topology and discordant ventriculoarterial connection. The common atrioventricular orifice was guarded by an effectively common valve, the right half being guarded by a well-formed three-leaflet valve, but the posterior and left lateral wall of the orifice being deficient of valvar leaflet tissue. The right ventricular inlet was a blind chamber, an imperforate dimple being seen which was surrounded by valvar remnants. The apical trabecular and outlet components of the right ventricle communicated with the left ventricle through an outlet ventricular septal defect in front of the anterosuperior leaflet of the atrioventricular valve, giving the potential clinically for the lesion to be misdiagnosed as double inlet left ventricle.

A superior and anterior location of the tricuspid valve in the setting of malalignment between the atrial and ventricular septal structures was the characteristic unifying morphologic feature of seven autopsied hearts with twisted atrioventricular connections. The peculiar angiocardiographic appearances of this lesion could be readily explained by the findings of unusual recesses in the right atrium, in the right ventricle, and in the left ventricle. The recess in the morphologically left ventricle was seen in each case at the right posterior part (or, in the hearts with left-handed ventricles, at the left part) of the chamber. Displacement of the right-sided atrioventricular valve far from the inferior caval vein (vena cava) had produced the recess in the morphologically right atrium; this feature was most prominent in the heart in which the atrioventricular connections were discordant. The recess within the right ventricular outflow tract was seen in four hearts, in all of which the inlet and apical trabecular components of the right ventricle were hypoplastic.

We quantitated the protective effect of verapamil on reperfusion injury in canine myocardial infarct using 111In-anticardiac myosin antibody and correlated to the electronmicroscopic findings. Experimental myocardial infarction was performed by one hour occlusion of the anterior descending coronary artery and followed by reperfusion. Saline or verapamil (0.6 mg/kg/hr) was started at 40 minutes after coronary artery occlusion and continued throughout the experiment. There was an inverse exponential relationship between anticardiac myosin uptake and regional coronary blood flow in both the control (r = -0.86) and the verapamil treated (r = -0.71) groups. Less uptake of 111In-anticardiac myosin antibody was observed in the verapamil treated group than in the control group of the regions where blood flow was lower than 30% of normal. In the control group, the myocardium showed signs of the typical contraction band necrosis. In the verapamil treated group, however, the myocardium contained fewer electron dense granules and mild degree of contraction bands.

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.