A Rare Case of Methotrexate Induced Pancreatitis in Ectopic Pregnancy / 이화의대지

Ectopic pregnancy (EP) refers to blastocyst implantation outside the uterine endometrium. EP is major cause of maternal morbidity and mortality. Treatment options include surgery, medical therapy with methotrexate, or expectant management. Methotrexate is the primary regimen used in cases of early, unruptured ectopic pregnancies. Most side effects of methotrexate are minor, including nausea, vomiting, abdominal discomfort, and photosensitive skin reaction. Serious side effects, including bone marrow suppression, and pulmonary fibrosis, are invariably observed when methotrexate is administered in high doses with frequent dosing intervals, in chemotherapeutic protocols for malignancy. These side effects are uncommon with the doses used to treat ectopic pregnancies. Since cases of methotrexate-induced pancreatitis are rare, we report a case of pancreatitis in a patient with EP treated with methotrexate and expect to consider pancreatitis as a side effect of methotrexate in a patient with upper abdominal pain undergoing methotrexate chemotherapy.

BMD42-2910, a Novel Benzoxazole Derivative, Shows a Potent Anti-prion Activity and Prolongs the Mean Survival in an Animal Model of Prion Disease

Prion diseases are a group of neurodegenerative and fatal central nervous system disorders. The pathogenic mechanism involves the conversion of cellular prion protein (PrPC) to an altered scrapie isoform (PrPSc), which accumulates in amyloid deposits in the brain. However, no therapeutic drugs have demonstrated efficacy in clinical trials. We previously reported that BMD42-29, a synthetic compound discovered in silico , is a novel anti-prion compound that inhibits the conversion of PrPC to protease K (PK)-resistant PrPSc fragments (PrPres). In the present study, 14 derivatives of BMD42-29 were obtained from BMD42-29 by modifying in the side chain by in silico feedback, with the aim to determine whether they improve anti-prion activity. These derivatives were assessed in a PrPSc-infected cell model and some derivatives were further tested using real timequaking induced conversion (RT-QuIC). Among them, BMD42-2910 showed high anti-prion activity at low concentrations in vitro and also no toxic effects in a mouse model. Interestingly, abundant PrPres was reduced in brains of mice infected with prion strain when treated with BMD42- 2910, and the mice survived longer than control mice and even that treated with BMD42-29. Finally, high binding affinity was predicted in the virtual binding sites (Asn159, Gln 160, Lys194, and Glu196) when PrPC was combined with BMD-42-2910. Our findings showed that BMD42-2910 sufficiently reduces PrPres generation in vitro and in vivo and may be a promising novel anti-prion compound.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report / 결핵및호흡기질환

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

Pulmonary Mucormycosis Treated Successfully with Posaconazole as Salvage Therapy / 계명의대학술지

Mucormycosis (formerly known as zygomycosis) is a life-threatening opportunistic mycosis that infects a broad range of hosts with qualitative or quantitative defects in innate immunity. The overall mortality rate of pulmonary mucormycosis is above 70%. The prognosis and outcome of pulmonary mucormycosis have not improved significantly over the last decade, mainly because of difficulty in early diagnosis and the limited activity of current antifungal agents against members of the order Mucorales. We report a case of pulmonary mucormycosis treated successfully with posaconazole as salvage therapy. We suggest that posaconazole may be considered as an alternative therapeutic approach in patients with invasive pulmonary mucormycosis who are unable to tolerate surgical treatment.

Micropapillary Lung Adenocarcinoma with Aerogenous Spread / 계명의대학술지

We experienced a case of micropapillary lung adenocarcinoma with aerogenous spread in a patient who was suspected of having interstitial pneumonia. To our knowledge, our case has not been described in the Korean literature. Our case indicates that clinicians cannot rule out the possibility of micropapillary lung adenocarcinoma with aerogenous spread in patients with a persistent presence of lesions in the lower left lung.

The Effects of Bronchoscope Diameter on the Diagnostic Yield of Transbronchial Lung Biopsy of Peripheral Pulmonary Nodules / 결핵및호흡기질환

BACKGROUND: Transbronchial lung biopsy (TBLB) is a valuable diagnostic tool for peripheral pulmonary lesions. The diagnostic yield of TBLB reportedly ranges from 41%-60%. Many studies demonstrated the various factors that influence the yield of TBLB, including size, location, and distance from the carina or pleura. However, no study has evaluated the effects of the bronchoscope diameter. We evaluated whether the bronchoscope diameter affected the diagnostic yield of TBLB. METHODS: We reviewed records from 178 patients who underwent TBLB using bronchoscopes of two different diameters (5.7 mm, thick outer diameter, Olympus BF-200; 4.9 mm, thin, BF-260). The fluoroscopic guidance rates, yield of TBLB and flexible bronchoscopy (FB) were compared between the two groups. Additionally, we compared the results of the procedures with respect to diagnosis, distance from the pleura, and size of the lesion. RESULTS: The results of fluoroscopic guidance, TBLB, and FB yield using thin diameter bronchoscope were significantly better than those obtained with a thick diameter bronchoscope (p=0.021, p=0.036, and p=0.010, respectively). Particularly, when the distance from the pleura was < or = 10 mm, success rates for fluoroscopic guidance and FB with thin bronchoscope were higher (p=0.013 and p=0.033, respectively), as compared to with thick bronchoscope. CONCLUSION: A thinner diameter bronchoscope increased the yield of bronchoscopy, and bronchial washing in conjunction with TBLB was useful in the diagnosis of peripheral pulmonary nodules.

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production / 대한해부학회지

The L-gulono-gamma-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.

Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-alpha/beta at the Initial Stage of Influenza A Virus (H3N2) Infection

L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-alpha/beta, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-alpha/beta, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-alpha/beta.

Relationship Between Survivors' Perceived Health Status Following Acute Coronary Syndrome and Depression Symptoms During Early Recovery Phase

PURPOSE: To examine and describe perceived health status and depression symptoms among Acute Coronary Syndrome (ACS) survivors, and to examine their relationship during survivors' recovery phase. METHODS: A prospective design was used to test changeability of the key variables over a 1-month period for a cohort group of 82 post ACS patients, prior to their hospital discharge (Time 1) and at 4 weeks post discharge (Time 2). The revised version of Short Form-12 Health Survey and Beck Depression Inventory were used to measure the perceived health status and depression symptoms. The data were collected between 2003 and 2004. RESULTS: Perceived health status including mental health and physical health significantly improved over the 4-week period (t=-2.58, p < .05). Perceived health status during the hospitalization and length of hospital stay were significant predictors of depression symptoms during the early recovery phase. CONCLUSIONS: Patients' own perceptions about their health status need to be closely evaluated during the hospitalization in order to reduce the occurrences of later depression symptoms. Consequently, reducing depression symptoms and improving perceived health status should be addressed both in acute and chronic phases of ACS.

Comparison of Cardiovascular Health Status and Health Behaviors in Korean Women based on Household Income

PURPOSE: In this study cardiovascular health status and health behavior of Korean women based on their household income were explored. METHODS: For this cross-sectional study, 91 women residing in the community were recruited to complete survey questionnaires and biophysical tests including blood pressure (BP), body mass index (BMI), body fat rate, waist circumference (WC), and blood chemistry tests. RESULTS: Compared to non-low income women (NLIW), low income women (LIW) were more likely to be older, less educated, and jobless, and further more LIW were postmenopause and reported having been diagnosed with hypertension or hypercholesterolemia. Significant differences were found in systolic BP, triglyceride level, BMI, body fat rate, and WC between the groups. Two fifths of the LIW had indications for metabolic syndrome. Their 10-yr risk estimate of myocardioal infarction or coronary death demonstrated a higher probability than that of NLIW. Although these significant differences were due to age gap between the groups, advanced age is known to be one of the key characteristics of LIW as well as a non-modifiable risk factor. CONCLUSION: Effective community programs for vulnerable women at risk of cardiovascular disease should be based on strategies targeting unhealthy behaviors and modifiable risk factors.

Estimate of Radiation Doses in MDCT Using Patient Weight / 의학물리

The purpose of this study provides measurements of radiation dose from MDCT of head, chest, abdomen and pelvic examinations. A series of dose quantities that are measured of patient weight to compare the dose received during MDCT examinations. Data collected included: weight together with CT dose descriptors, volume CT dose index (CTDIvol) and dose length product (DLP). The effective dose was also estimated and served as collective dose estimation data. Data from 1,774 adult patients attending for a CT examination of the head (n=520) or chest (n=531) or abdomen (n=724) was obtained from spiral CT units using a same CT protocol. Mean values of CTDIvol was a range of 48.6 mGy for head and 6.9, 10.5 mGy for chest, abdomen examinations, respectively. And mean values of DLP was range of 1,604 mGy.cm for head, 250 mGy.cm for chest, 575 mGy.cm for abdomen examinations, respectively. Mean effective dose values for head, chest, abdominal CT were 3.6, 4.2, and 8.6 mSv, respectively. The degree of CTDIvol and DLP was a positive correlation with weight. And there was a positive correlation for weight versus CTDIvol (r2=0.62), DLP (r2=0.694) in chest. And head was also positive correlation with weight versus CTDIvol (r2=0.691), DLP (r2=0.741). We conclude that CTDIvol and DLP is an important determinant of weight within the CT examinations. The results for this study suggest that CT protocol should be tailored according to patient weight.

Integrative Analysis of Microarray Data with Gene Ontology to Select Perturbed Molecular Functions using Gene Ontology Functional Code

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selectedmolecular functions include several known breast cancer- related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

Deep hypothermic total circulatory arrest (DHCA) under total intravenous anesthesia for giant basilar aneurysm clipping : A case report

The prevalence of unruptured intracranial aneurysm varies between 3.6% and 6%.Aneurysms in the posterior circulation, inaccessible by normothermic surgical clipping and giant aneurysms require direct surgical clipping under hypothermic circulatory arrest for cerebral protection.The authors describe a case of giant basilar aneurysm clipping requiring deep hypothermic total circulatory arrest under total intravenous anesthesia.The patient was a 43-year-old female with a giant aneurysm at the tip of the basilar artery.Total intravenous anesthesia with propofol (average effect site concentration 4 mcg/ml) and remifentanil (average effect site concentration 3 ng/ml) and deep hypothermic total circulatory arrest were performed.Neurophysiologic function was monitored by electroencephalography, and somatosensory and motor evoked potentials. Cardiac and coagulation profiles showed no significant changes. The aneurysm was successfully clipped but the patient expired. Further collations of clinical experiences should enable the identification of an optimal means of anesthetic management during complex cerebrovascular surgery.

Microarray Data Analysis of Perturbed Pathways in Breast Cancer Tissues

Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.