A Case of Lupus-Related Hepatitis Mimicking Autoimmune Hepatitis / 대한내과학회지

Patients with systemic lupus erythematosus (SLE) have a 25% to 50% incidence of abnormal findings on liver function tests. The main causes of abnormal liver function in patients with SLE are viral hepatitis, drug-induced toxic hepatitis, and fatty liver. However, hepatic involvement due to the pathogenic process of SLE is rare. In such conditions, lupus-related hepatitis must be distinguished from autoimmune hepatitis, which is a type of primary liver disease characterized by similar clinical manifestations and autoimmune profiles. Relationships between hepatic involvement of SLE and autoimmune hepatitis remain to be elucidated. We report a case of lupus-related hepatitis mimicking autoimmune hepatitis.

Clinical Characteristics of Elderly Onset Rheumatoid Arthritis

BACKGROUND: Elderly onset rheumatoid arthritis (EORA) affects people older than 60 years of age and is different from younger onset rheumatoid arthritis (YORA) in several aspects. EORA is seen in each sex equally, has more large joint involvement and is associated with a higher erythrocyte sedimentation rate (ESR). In this study, we compared the clinical and laboratory data of these two conditions. METHODS: Our subjects included 230 patients meeting the American College of Rheumatology criteria for rheumatoid arthritis. We compared the clinical manifestation, medication history and laboratory data including rheumatoid factor, anti-nuclear antibody, ESR, C-reactive protein and total sharp score of EORA and YORA. RESULTS: The male to female ratio was 1:2.5 in EORA and 1:5.6 in YORA (p=0.016). The mean age was 74+/-5.3 years in EORA and 47+/-8.9 years in YORA. ESR was higher for EORA (52.8+/-35.6 mm/hr) than for YORA (40.2+/-29.2 mm/hr) (p=0.004). A positive RF was seen more often in EORA (75%) than in YORA (67%) (p=0.027). Shoulder joint pain was more common in EORA (41.0%) than in YORA (21.6%) (p=0.001) as was knee joint pain, 77.1% and 48.8%(p<0.001), respectively. CONCLUSION: EORA showed a relatively higher incidence in males and had more large joint involvement than YORA. The higher abnormal values of ESR and rheumatoid factor seen in EORA might be associated with poor prognosis.

Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) in a Patient with Rheumatoid Arthritis / 대한류마티스학회지

Interstitial lung disease (ILD) is one of the common extra-articular manifestations of rheumatoid arthritis (RA). Bronchiolitis obliterans with organizing pneumonia (BOOP) is one type of ILD, and this is characterized by the proliferation of granulation tissue in the bronchioles, alveolar ducts and some alveoli and interstitial infiltration by chronic inflammatory cells. It develops as a manifestation of RA or as a side effect of anti-rheumatic drugs in patients with RA. We experienced a 41-year-old female patient with RA who developed BOOP during the treatment with methotrexate and bucillamine. She presented with cough and sputum for several months and pleuritic chest pain for one week. The chest radiograph showed bilateral multifocal consolidations. She received thoracoscopic biopsy and her pulmonary infiltrations resolved after the treatment with corticosteroid.

Listeria Monocytogenes Meningitis Presenting with Bilateral Abducens Nerve Palsy in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

Infection still remains a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Patients with SLE are well known to have an increased risk of various opportunistic infections, which can be fatal. Central nervous system (CNS) infections such as meningitis are rare complications to SLE. On occasion, nonspecific neurologic manifestations of infectious meningitis in SLE patients can be confused with neuropsychiatric lupus. Listeria monocytogenes is a less-commonly identified organism causing meningitis in SLE patients. Here, we describe a case of Listeria monocytogenes meningitis presenting with bilateral abducens nerve (sixth cranial nerve) palsy in a patient with SLE, who was successfully treated with systemic antibiotics.

Simultaneous Occurrence of Cytomegalovirus Pneumonitis and Retinitis in a Patient with Dermatomyositis / 대한류마티스학회지

Cytomegalovirus (CMV) infection commonly affects patients who are in an immunocompromised state, such as acquired immune deficiency syndrome (AIDS) and during organ transplantation. Although cytomegalovirus infection does not occur frequently, it is a major cause of morbidity and mortality in patients suffering with connective tissue diseases, including dermatomyositis. Cytomegalovirus pneumonitis and retinitis has been rarely reported in patients with dermatomyositis. We report here on an usual case involving the simultaneous occurrence of cytomegalovirus pneumonitis and retinitis in a 39-year-old female with dermatomyositis, and this woman had been treated with steroids and immunosuppressive agents for the previous 5 months.

The Efficacy of Enoxaparin for the Prevention of a Pulmonary Thromboembolism in a Skin-sparing Mastectomy with Immediate Reconstruction in Breast Cancer / 한국유방암학회지

PURPOSE: Performance of a skin-sparing mastectomy with immediate reconstruction provides psychological satisfaction and good cosmetic outcome for patients with breast cancer. However, this is a lengthy procedure to perform, and there is increased risk of pulmonary thromboembolism (PTE). The purpose of this study was to evaluate the efficiency of the use of low molecular weight heparins (enoxaparin) for prophylaxis against a pulmomary thromboembolism followed by mastectomy with an immediate transverse rectus abdominis myocutaneous flap (TRAM) in breast cancer. METHODS: A total of 123 patients underwent a skin-sparing mastectomy with an immediate TRAM. The "non-enoxaparin group" wore compression stockings for PTE prophylaxis and the "enoxaparin group" received enoxaparin (40 mg SC injection, once daily starting 2 hr before surgery and continuing for 6 days postoperatively) in conjunction with the use of compression stockings. Lung perfusion, inhalation scans, and serum D-dimer assays were performed on postoperative day 3. If findings were clinically suspicious or intermediate to high probability of a PTE in a lungs scan, embolism computed tomography was performed. Patients were prospectively investigated according to the clinicopathological data. We compared the incidence of PTE and hemorrhagic complications between the two groups. RESULTS: There were no significant clinicopathological differences between the two groups. Eleven patients developed a PTE (nine patients in the non-enoxaparin group and two patients in the enoxaparin group). The prevalence rate of a PTE was 17.3% and 3.2% for each group, respectively (p=0.01). One patient in the non-enoxaparin group required a second operation for bleeding control and three patients in the enoxaparin group needed transfusions. There were minor hemorrhagic complications in the enoxaparin group that improved after supportive management. CONCLUSION: Although there were minor hemorrhagic complications, enoxaparin is safe and effective in a preventing PTE in patients that undergo immediate reconstruction after a skin-sparing mastectomy.

Expression of Cyclin D1 and bcl-2 in Infiltrative Ductal Carcinoma of the Breast: Their Correlations and Clinical implications / 한국유방암학회지

PURPOSE: Cyclin D1 and bcl-2 are involved in cell proliferation and apoptosis in tumor development and are commonly expressed in breast cancer. But there are few clinical reports on the correlation between cyclin D1 and bcl-2 expression. This study was designed to analyze the correlations of cyclin D1 and bcl-2 and their clinical implications in breast cancer. METHODS: Immunohistochemical expression of cyclin D1 and bcl-2 were studied in 342 infiltrative ductal carcinoma cases and were compared with clinicopathologic parameters such as age, tumor size, histologic grade, lymph node status, p53, c-erbB2 and hormone receptors. RESULTS: Cyclin D1 expression was found in 86 of 342 cases (25.1%). Bcl-2 was positive in 227 of 342 cases (66.4%). Bcl-2 overexpression was associated with the high expression of cyclin D1 (p=0.001). Correlation was detected between both cyclin D1 and bcl-2 and hormone receptor positivity (p<0.001). There was a reverse correlation between bcl-2 and histologic grade, p53, c-erbB2. And the bcl-2 overexpression group showed better disease free survival rates at 3-year follow up. CONCLUSION: Higher expression of cyclin D1 was associated with bcl-2 overexpression. Positive estrogen receptor expression was associated with high cyclin D1 and bcl-2 expression. Bcl-2 tends to correlate with a positive clinical outcome.

Expression of VEGF-C and LYVE-1 in breast cancer tissues / 한국유방암학회지

PURPOSE: The aim of this study was to assess the expression of VEGF-C (vascular endothelial growth factor-C) and LYVE-1 (lymphatic vessel endothelial HA receptor-1) mRNA in human breast cancer, and to compare the expression of VEGF-C protein and VEGF-C, LYVE-1 mRNA with the clinico-pathological outcomes. METHODS: RT-PCR was carried on the VEGF-C, LYVE-1 mRNA drawn from three samples of adjacent normal breast tissues, the MCF-7 breast cancer cell line and 39 breast cancer tissues. Immunohistochemical staining was done to detect the expression of VEGF-C protein in 39 cancer tissues and in 5 benign tissues with using well preserved, paraffin embedded tissues. The clinico-pathological findings were retrospectively reviewed for menopausal status, lymphatic invasion, hormonal status, the expression of p53 and c-erbB2. RESULTS: RT-PCR analysis revealed the expression of VEGF-C mRNA in 22 of 39 (56.4%) and LYVE-1 mRNA in 19 of 39 breast cancer tissues (48.7%). The expression of VEGF-C mRNA was positive in all cases except for one in LYVE-1 mRNA positive case, this revealed good correlation between the two molecules. Immunohistochemical analysis revealed that VEGF-C protein was expressed only in the breast cancer cells, with specific VEGF-C staining evident in 10 of 39 (25.6%). There was no significant correlation between VEGF-C, LYVE-1 mRNA expressions and the other pathologic variables. However, VEGF-C protein expression was negative in the group with a postmenopausal status, positive estrogen receptor and negative c-erbB2 significantly. CONCLUSIONS: VEGF-C mRNA seems to be related to the lymphangiogenetic marker-LYVE-1 mRNA and the amplification of the VEGF-C may be correlated with some clinico-pathological factors in the breast cancer.

Expression of VEGF-C and LYVE-1 in breast cancer tissues / 한국유방암학회지

PURPOSE: The aim of this study was to assess the expression of VEGF-C (vascular endothelial growth factor-C) and LYVE-1 (lymphatic vessel endothelial HA receptor-1) mRNA in human breast cancer, and to compare the expression of VEGF-C protein and VEGF-C, LYVE-1 mRNA with the clinico-pathological outcomes. METHODS: RT-PCR was carried on the VEGF-C, LYVE-1 mRNA drawn from three samples of adjacent normal breast tissues, the MCF-7 breast cancer cell line and 39 breast cancer tissues. Immunohistochemical staining was done to detect the expression of VEGF-C protein in 39 cancer tissues and in 5 benign tissues with using well preserved, paraffin embedded tissues. The clinico-pathological findings were retrospectively reviewed for menopausal status, lymphatic invasion, hormonal status, the expression of p53 and c-erbB2. RESULTS: RT-PCR analysis revealed the expression of VEGF-C mRNA in 22 of 39 (56.4%) and LYVE-1 mRNA in 19 of 39 breast cancer tissues (48.7%). The expression of VEGF-C mRNA was positive in all cases except for one in LYVE-1 mRNA positive case, this revealed good correlation between the two molecules. Immunohistochemical analysis revealed that VEGF-C protein was expressed only in the breast cancer cells, with specific VEGF-C staining evident in 10 of 39 (25.6%). There was no significant correlation between VEGF-C, LYVE-1 mRNA expressions and the other pathologic variables. However, VEGF-C protein expression was negative in the group with a postmenopausal status, positive estrogen receptor and negative c-erbB2 significantly. CONCLUSIONS: VEGF-C mRNA seems to be related to the lymphangiogenetic marker-LYVE-1 mRNA and the amplification of the VEGF-C may be correlated with some clinico-pathological factors in the breast cancer.

A case of extrapontine myelinolysis associated with hyperosmolar hyperglycemic syndrome / 대한내과학회지

Hyperosmolar hyperglycemic syndrome (HHS) or hyperglycemic hyperosmolar nonketotic coma, an acute complication of type 2 diabetes mellitus, is commonly associated with hypernatremia. According to the treatment guideline of HHS and hypernatremia, plasma glucose and sodium concentration should be lowered at the recommended correction rate to prevent cerebral edema and, rarely, central pontine myelinolysis (CPM) or extrapontine myelinolysis (EPM). Recently we experienced a case of HHS with initial corrected serum sodium concentration of 198.5 mEq/L. The hypernatremia was corrected too rapidly on the first and second hospital days and the patient showed recent memory disturbance and difficulty in communication on the third hospital day. Brain MRI revealed abnormal signal intensities in the extrapontine areas, in favor of a diagnosis of EPM. We concluded that EPM of this case was induced by the rapid correction of hypernatremia.

Correlation between Ultrasonographic Findings and The Response to Corticosteroid Injection in Pes Anserinus Tendinobursitis Syndrome in Knee Osteoarthritis Patients

The objectives of this study were to assess the ultrasonographic (US) findings in patients with knee osteoarthritis (OA) with pes anserinus tendinitis or bursitis (PATB) syndrome and to determine the correlation between the US findings and the response to local corticosteroid injection. We prospectively studied 26 patients with knee OA with clinically diagnosed PATB syndrome. A linear array 7 MHz transducer was used for US examination of the knee. Seventeen patients were injected locally with tramcinolone acetonide in the anserine bursa area. Response to local corticosteroid injection was evaluated by pain visual analog scale (VAS), Western Ontario and MacMaster (WOMAC) osteoarthritis index and Global patient/physician assessment using Likert scale. On US examination, only 2 patients (8.7%) showed evidence of PATB. Pain VAS, WOMAC pain index and WOMAC physical function index improved significantly after corticosteroid injection. Global patient assessment revealed that 2 patients showed best response, 6 good, 1 fair, 8 the same, and none worse. It is of note that the 2 patients who showed the best response were those who showed US evidence of PATB. This finding shows that US can serve as a useful diagnostic tool for guiding treatment in PATB syndrome of OA patients.

Correlation of Immunohistochemical Expression of MDR1, MRP1, Topoisomerase IIalpha with Prognostic Factors and Histoculture Drug Response Assay (HDRA) Result in Breast Carcinoma / 한국유방암학회지

PURPOSE: Drug resistance plays an important role in the failure of chemotherapy in breast cancer. The purpose of the study was to investigate the chemosensitive and chemoresistance indices of breast carcinomas and see if the in vitro chemosensitivity test correlated with the prognostic indices. METHODS: The immunohistochemical expressions of MDR1, MRP1 and topoisomerase IIalpha(topo IIalpha) were studied and then correlated these with the in vitro chemosensitivities using the histoculture drug response assay (HDRA) and clinicopathological factors in 51 breast carcinomas. RESULTS: In the breast carcinomas examined, the immunohistochemical expressions of MDR1, MRP1 and topo II alpha were strongly observed in 26 (51.0%), 16 (32.0%), 15 (31.3%) carcinomas, respectively. The MRP1 was more frequently expressed in poorly differentiated carcinomas (P= 0.006), and those of MDR1 and topo II alpha were more frequently observed in tumor overexpressing cerbB2 (P=0.038, P=0.036). The expression of MDR1 was related to that of topo II alpha (P=0.015). Comparing these markers with the in vitro chemosensitivities to cyclophosphamide, 5-FU, adriamycin, taxol and taxotere, no correlations were found between the expression of MDR1, MRP1, and topo II alpha but from the chemosensitivity using the HDRA, the growth inhibition rate for cyclophosphamide was higher in MRP1 expressing carcinomas (P=0.009). CONCLUSION: MDR1, MRP1 and topo II alpha were all found to be associated with the poor prognostic indices, but assessment of their immunohistochemical expressions did not allow for prediction of the response to chemotherapy by the in vitro chemosensitivity test in breast carcinomas.

Prologation of c-Jun N-Terminal Kinase is Associated with Cell Death Induced by Tumor Necrosis Factor Alpha in Human Chondrocytes

The aim of this study was to elucidate the role of JNK signaling pathway involved in tumor necrosis factor-alpha (TNF-alpha)-induced death of chondrocytes. Primary chondrocyte cultures were obtained from human knee osteoarthritis cartilages. First passage chondrocytes were treated with TNF-alpha and various potentiators, and cell death was measured with MTT assay. C-Jun N terminal kinase (JNK) activation was investigated with the solid phase kinase assay. Expression of apoptosis-related molecule was assayed with Western blot. Chondrocytes were resistant to TNF-alpha-induced cell death. In contrast, pretreatment with actinomycin D, the phosphatase inhibitor vanadate or MAP kinase phosphatase-1 (MKP-1) inhibitor Ro318220 invariably led to chondrocyte death. While TNF-alpha alone stimulated a single, brief JNK activity, a second JNK peak was observed when the cells were pretreated with actinomycin D. When the cells were pretreated with vanadate or Ro318220, TNF-alpha-induced JNK activation was greatly prolonged, which was associated with the induction of cell death. The expression of Bcl-2 and Mcl-1 decreased significantly in conditions of cell death. In conclusions, our data suggest that chondrocyte death induced by TNF-alpha is associated with sustained JNK activation. This effect may be due to downregulation of TNF-alpha induced phosphatase that inactivates JNK and of Bcl-2 family proteins.

Skin-sparing Mastectomy with Immediate Breast Reconstruction for the Treatment of Advanced Breast Cancer / 한국유방암학회지

PURPOSE: This study was performed to show the several clinical variables before and after the surgery that need to be considered for patient selection and whether there is an increased possibility of recurrence after surgery and whether this possibility can be reduced when adjuvant treatment is applied. METHODS: The outcome of SSM with immediate breast reconstruction, using follow-up data of cases performed at Asan Medical Center between September, 1996 and December, 2002, were retrospectively assessed and pathologically advanced breast cancer patients (stage III) were analyzed separately. RESULTS: 191 patients had undergone SSM with immediate reconstruction during the study period. The percentage of cases stage III was 15.2% (29 cases). Among these patients, 6 (20.7%) were suspected of being in the early stages of breast cancer prior to the surgery. The mean age of the advanced breast cancer patients was 37 years. Immediate breast reconstruction consisted of a pedicled TRAM flap (n=24), a insertion of tissue expander (n=4) or direct implant (n=1). Radiotherapy was performed in 16 patients (53.3%) and chemotherapy was conducted without delay in all case. With a median length of follow-up of 36.1 months for 22 patients, who under went the operation until December, 2001, local recurrence was 4.5% (1/22) with successful local treatment, and distant metastasis was 13.7% (3/22). There was no difference in the disease free survival compared to that of the non-reconstruction group (P=0.093). CONCLUSION: SSM with immediate reconstruction seems safe and effective for patients with advanced breast cancer. However an accurate preoperative assessment of the extent of the disease and discussion for the planning of treatment between surgeon and patient is required.

A Case of Masked Hypoglycemia during Lactic Acidosis / 대한내분비학회지

Severe hypoglycemia induces neuroglycopenic symptoms, including mental alteration, as glucose is the exclusive fuel for the central nervous system. However, some reports have shown that non-glucose fuels, like lactates and ketones, could be utilized by the brain during severe hypoglycemia. Herein, a case of extreme hypoglycemia in a 44-year old woman, subsequently diagnosed as congestive heart failure accompanied by ischemic hepatitis and lactic acidosis, is presented. In two episodes of extreme hypoglycemia, she was fully alert without obvious neurological deficits. In this unusual case, an increased supply of lactate might have maintained the cerebral function and prevented cerebral injury during the hypoglycemia that was induced as a result of starvation and hepatic and cardiac dysfunctions

A Case of Masked Hypoglycemia during Lactic Acidosis / 대한내분비학회지

Severe hypoglycemia induces neuroglycopenic symptoms, including mental alteration, as glucose is the exclusive fuel for the central nervous system. However, some reports have shown that non-glucose fuels, like lactates and ketones, could be utilized by the brain during severe hypoglycemia. Herein, a case of extreme hypoglycemia in a 44-year old woman, subsequently diagnosed as congestive heart failure accompanied by ischemic hepatitis and lactic acidosis, is presented. In two episodes of extreme hypoglycemia, she was fully alert without obvious neurological deficits. In this unusual case, an increased supply of lactate might have maintained the cerebral function and prevented cerebral injury during the hypoglycemia that was induced as a result of starvation and hepatic and cardiac dysfunctions

A case of bronchial asthma due to Tyrophagus putrescentiae in a non occupational setting / 천식및알레르기

Storage mites are believed one of the most important allergens in farmers and rural regions. Tyrophagus putrescentiae, belonging to storage mites, is found not only within storehouses but also in the house dust, and the third most common mites following Dermatophagoides farinae and Dermatophagoides pteronyssinus in house dust in Korea. The sensitization rate to Tyrophagus putrescentiae was reported as high as that of house dust mite in patients visiting the allergy clinic in large cities in Korea. We experienced a 69-year-old man who had suffered from dyspnea, wheezing, and coughing for 10 years. He retired from the teaching profession, and had lived in a large city, Deajeon. The skin prick test showed a positive reaction to Tyrophagus putrescentiae and negative reactions to house dust mites. The bronchial challenge test with Tyrophagus putrescentiae showed late asthmatic reaction. We confirmed a Tyrophagus putrescentiae-induced asthma in non occupational setting.

Prevalence of BRCA1 and BRCA2 Mutations in Korean Breast Cancer Patients

The incidence of breast cancer in Korea has been increasing in recent years, such that it is now the most common female cancer. Breast cancer in Korea is characterized by an earlier age of onset than in Western countries, suggesting that it would be related with genetic background. We assayed germline mutations in the BRCA genes to evaluate their genetic pathology in Korean breast cancer patients. The study subjects consisted of 173 patients at clinically higher risk and 109 unselected patients. Germline mutations in the entire coding sequences of the BRCA1 and BRCA2 genes were analyzed by Conformation-Sensitive Gel Electrophoresis (CSGE), and any aberrantly-sized band was sequenced. BRCA mutations were present in 12.7% of the high risk patients, compared with 2.8% of the unselected patients. Among high risk patients, mutations were most prevalent in patients with a family history of breast or first-degree ovarian cancer (22.1%), followed by those with male breast cancer (20%), bilateral breast cancer (20%), multiple organ cancer including breast (13%) and younger breast cancer patients (aged<35 yr) (8.1%). Moreover, BRCA mutations were detected in 34.8% of patients having two highrisk factors. These findings suggest that BRCA gene mutation analysis should be performed on Korean patients with high-risk factors for breast cancer.

A Case of Pedunculated Leiomyoma Found during Colonoscopic Examination for Anal Bleeding / 대한소화기학회지

Gastrointestinal leiomyomas are commonly found in the stomach, and but 3% of them arises from the colon. Colonic leiomyomas are often found incidentally during colonoscopic examination. Most of patients with colonic leiomyoma are asymptomatic, but patients with large size leiomyoma occasionally have abdominal mass, hemorrhage, intestinal obstruction or perforation. Pedunculated leiomyomatous polyp is rare. Leiomyomatous polyps are occasionally misjudged as adenomatous polyps by endoscopist. We report a case of pedunculated leiomyomatous colonic polyp in 65 year-old female patient. She has complained of intermittent hematochezia and lower abdominal discomfort for 5 months. During colonoscopy, an 1 cm sized long pedunculated polyp at the splenic flexure was detected. It was removed by colonoscopic snare polypectomy. Leiomyomatous polyp was confirmed by microscopic and immunohistochemical findings.

A Case of Gastritis Cystica Profunda Associated with High Grade Tubular Adenoma / 대한소화기학회지

Gastritis cystica profunda is usually characterized by hyperplastic and cystic dilatation of pseudopyloric gland with submucosal invasion. These lesions possess malignant histologic features as metaplastic and even dysplastic alteration can be observed, however they usually exhibit benign behavior. Macroscopically, gastritis cystica profunda may present as a submucosal tumor or as a polyp. In rare case, however, it can be found as a giant mucosal fold. The proposed pathogenesis of lesion relates to ischemia, chronic inflammation, and the presence of foreign body. Herein, we report a case of gastritis cystica profunda associated with high grade tubular adenoma in a patient without antecedent surgery.