The ability to cope with changing environments is critical for healthy functioning, yet this flexibility is impaired in many neuropsychiatric disorders. However, neural mechanisms underlying flexible behavior remain elusive. Here, we report that oscillatory dynamics in the medial prefrontal cortex (mPFC) support learning to flexibly overcome established behavioral bias. Mice performed a delayed non-match-to-sample task that required trial-by-trial adjustment of arm choice strategy despite persistent arm bias. Decoding analysis of delay-period local field potentials (LFPs) and single-unit activities revealed evolving neural representations across trials as mice adapted to the task. Notably, mPFC neurons modulated by theta (4~12 Hz) bursts selectively encoded upcoming choice information after acquiring the new rule. In contrast, beta (12~30 Hz) bursts correlated with perseverative behavior and appeared to inhibit theta-modulated neuronal firing in mice showing adaptive behavior. These theta and beta bursts were temporally separated over the delay period, reflecting a dynamic gating mechanism. Thus, beta bursts shape neuronal ensembles that are modulated by theta bursts to facilitate flexible learning. This dynamic interaction provides a mechanistic basis for cognitive flexibility and provides insights into cognitive rigidity seen in neuropsychiatric disorders such as schizophrenia and autism.

Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.

Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.

PURPOSE: The characteristics of hypoparathyroidism in patients with Hashimoto thyroiditis (HT) after total thyroidectomy are not well established. The aim of this study was to investigate the relationship between hypoparathyroidism and loss of parathyroid glands in patients with or without HT who underwent total thyroidectomy. METHODS: Patients who underwent total thyroidectomy were divided into two groups; with HT (n=166) and without HT (n=526). Clinicopathologic characteristics were compared between the two groups. RESULTS: The mean numbers of parathyroid glands in specimens were significantly smaller in the with HT group than in the without HT group (0.34+/-0.51 vs. 0.42+/-0.58, P=0.003). The rate of transient hypoparathyroidism was significantly higher in the with HT group than in the without HT group (51.8% vs. 34.6%, P=0.000). Serum total calcium levels in patients who experienced transient hypoparathyroidism did not differ significantly between groups (P=0.335). The incidence of transient hypoparathyroidism of patients who preserved all four parathyroid glands or sacrificed one parathyroid gland was higher in the with HT group than in the without HT group, although that of patients who sacrificed two or more parathyroid glands was similar between groups. The incidence of permanent hypoparathyroidism in the two groups did not differ (P=0.546). CONCLUSION: Patients with HT had a higher rate of transient hypoparathyroidism after total thyroidectomy, particularly patients who preserved all four or three parathyroid glands. It is likely that the blood supply to the parathyroid gland might be vulnerable in patients with HT. Therefore, even though all parathyroid glands were preserved, careful monitoring of hypoparathyroidism is necessary after total thyroidectomy in patients with HT.
Calcium ; Hashimoto Disease* ; Humans ; Hypoparathyroidism* ; Incidence ; Parathyroid Glands ; Thyroidectomy*

This report describes a rare case of a patient with splenic tuberculosis (TB) who developed spontaneous splenic rupture after 10 weeks of antituberculous chemotherapy. The patient responded well to the antituberculous regimen prior to the spontaneous splenic rupture. We considered a paradoxical reaction as a cause of the splenic rupture. The patient underwent splenectomy and continuously received initial antituberculous drugs without change. To the best of our knowledge, this is the first report of spontaneous splenic rupture as a paradoxical reaction to antituberculous chemotherapy in an immunocompetent host with splenic TB.
Disease Progression ; Drug Therapy ; Humans ; Splenectomy ; Splenic Rupture* ; Tuberculosis ; Tuberculosis, Splenic*

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.
Antibodies, Monoclonal, Humanized ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Trastuzumab

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.
Antibodies, Monoclonal, Humanized ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Trastuzumab

PURPOSE: Nearly half of all breast cancers are treated with breast conserving therapy (BCT). The purpose of this study was to identify the risk factors for ipsilateral breast tumor recurrence (IBTR) after BCT in T1 and T2 breast cancer patients. METHODS: The medical records of 294 T1 or T2 breast cancer patients who underwent BCT at Seoul National University Hospital between January 1998 and December 2002 were retrospectively reviewed. Kaplan-Meier curves and Cox proportional regression analysis were used to identify the significant clinicopathologic factors that influence IBTR. RESULTS: Among the 294 patients, 12 patients (4.8%) developed IBTR after a median follow-up of 82 months. Univariate analysis demonstrated that younger age (< or =35 year) had significant associations with IBTR (p=0.006). Tumor size, lymph node status, histologic grade, extensive intraductal component, lymphovascular invasion, and close resection margins were not significant factor associated with IBTR. The triple negative breast cancer subtype also did not have significant association with IBTR. Multivariate analysis showed that the younger age at diagnosis was a significant predictor of IBTR with a HR of 3.86 (p=0.036; 95% CI, 1.09-13.60). CONCLUSION: Younger age at diagnosis (< or =35) may be associated with an increased risk of IBTR in patients who underwent BCT.
Age Factors ; Breast ; Breast Neoplasms ; Follow-Up Studies ; Humans ; Lymph Nodes ; Medical Records ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Recurrence ; Retrospective Studies ; Risk Factors

PURPOSE: Breast cancer in male is uncommon, accounting for approximately 1% of all breast cancer and less than 1.5% of all the malignant neoplasms in males. The information concerned with the treatment of male breast cancer is limited. The objective of this study is to evaluate the histopathologic characteristics and clinical outcome of male breast cancer patients. METHODS: We retrospectively analyzed the medical record of 17 male breast cancer patients who had been operated on Seoul National University Hospital between 1996 and 2006. RESULTS: The peak age of incidence was the 6th decade and the mean age of the patients was 56.2 yr. The most common symptom was a palpable mass and the mean duration of symptoms was 13 months. Fifty-three percent of the patients were stage 0 or I. Mastectomy was performed in 15 cases and lumpectomy was performed in 2 cases. Twelve patients received adjuvant hormonal therapy. The median duration of follow up was 28 months. Of the two patients with distant relapse, one patient died due to multiple metastasis and the other patient is still alive. The other patients are still alive without any evidence of metastasis or recurrence. CONCLUSION: Active diagnosis, appropriate treatments (surgery and adjuvant therapy) and close follow up are necessary for male patients who have a palpable mass in their breast.
Breast ; Breast Neoplasms ; Breast Neoplasms, Male* ; Diagnosis ; Follow-Up Studies ; Humans ; Incidence ; Male ; Male* ; Mastectomy ; Mastectomy, Segmental ; Medical Records ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Seoul

PURPOSE: We aimed to assess the concordance of the immunohistochemical profiles of core biopsy before administrating neoadjuvant chemotherapy with that of the surgical specimens after a definitive operation for breast cancer. METHODS: We retrospectively reviewed the estrogen receptor (ER), progesterone receptor (PR), and HER-2 expressions in 130 consecutive patients who received neoadjuvant chemotherapy and were followed by surgery during the period between February 2002 and March 2006. The pathologic complete tumor response rate for this group was 4.6% (6/130). Both the pre- and post-operative immunohistochemical profiles were available in 32 of the 124 patients (25.8%). Immunohistochemical staining was done on the core biopsies before chemotherapy and on the surgical specimens after operation. RESULTS: There were 12 markers from 11 patients that were altered out of the 96 total markers (ER, PR, or HER-2) from 32 patients: 2 ER (2/12, 16.7%), 4 PR (4/12, 33.3%), and 6 HER-2 (6/12, 50.0%). One patient simultaneously had changes in the expressions of PR and HER-2. Conversion of the hormone receptor status occurred in 3 patients (3/32, 9.4%): this was positive to negative in two, and vice versa in one. In addition, there were 6 conversions (6/32, 18.8%) of the HER-2 status from negative to positive. CONCLUSION: The hormone receptor status changed in 9.4% of the 32 patients and the HER-2 status changed in 18.8% of the 32 patients after neoadjuvant chemotherapy. We have concluded that conducting only a single immunohistochemical study about ER, PR, and HER-2 may not be enough to exactly estimate the tumor marker status in the neoadjuvant setting.
Biopsy ; Breast Neoplasms* ; Breast* ; Drug Therapy* ; Estrogens* ; Humans ; Receptors, Progesterone* ; Retrospective Studies