OBJECTIVE: Removal of blood from subarachnoid space with a lumbar drainage (LD) may decrease development of cerebral vasospasm. We evaluated the effectiveness of a LD for a clinical vasospasm and outcomes after clipping of aneurysmal subarachnoid hemorrhage (SAH). METHODS: Between July 2008 and July 2013, 234 patients were included in this study. The LD group consisted of 126 patients, 108 patients in the non LD group. We investigated outcomes as follow : 1) clinical vasospasm, 2) angioplasty, 3) cerebral infarction, 4) Glasgow outcome scale (GOS) score at discharge, 5) GOS score at 6-month follow-up, and 6) mortality. RESULTS: Clinical vasospasm occurred in 19% of the LD group and 42% of the non LD group (p<0.001). Angioplasty was performed in 17% of the LD group and 38% of the non LD group (p=0.001). Cerebral infarctions were detected in 29% and 54% of each group respectively (p<0.001). The proportion of GOS score 5 at 6 month follow-up in the LD group was 69%, and it was 58% in the non LD group (p=0.001). Mortality rate showed 5% and 10% in each group respectively. But, there was no difference in shunt between the two groups. CONCLUSION: LD after aneurysmal SAH shows marked reduction of clinical vasospasm and need for angioplasty. With this technique we have shown favorable GOS score at 6 month follow-up.
Aneurysm ; Angioplasty ; Cerebral Infarction ; Cerebrospinal Fluid* ; Drainage* ; Follow-Up Studies ; Glasgow Outcome Scale ; Humans ; Mortality ; Subarachnoid Hemorrhage* ; Subarachnoid Space ; Surgical Instruments* ; Vasospasm, Intracranial*

BACKGROUND AND PURPOSE: It has been suggested that oxidative stress is one of the pathomechanisms underlying amyotrophic lateral sclerosis (ALS), and thus antioxidants such as uric acid (UA) that could reduce oxidative stress might be beneficial in the prevention or treatment of this disease. The objective of this study was to prospectively investigate serum UA levels in Korean ALS patients and to relate them to disease progression. METHODS: ALS patients and healthy controls who were individually well-matched for sex, age, and body mass index (BMI) underwent blood testing for serum UA levels, and analyzed whether UA levels were correlated with the disease status of the patients, as defined by the ALS Functional Rating Scale-Revised (ALSFRS-R). RESULTS: The study included 136 ALS patients and 136 matched controls. The UA level was lower in the ALS patients (4.50+/-1.17 mg/dL, mean+/-SD) than in the controls (5.51+/-1.22 mg/dL; p<0.001). Among the ALS patients, the level of UA acid was inversely correlated with the rate of disease progression (decrease in ALSFRS-R score). Kaplan-Meier analysis revealed that a better survival rate was more strongly correlated with top-tertile levels of serum UA than with bottom-tertile levels (log-rank test: p=0.035). CONCLUSIONS: ALS patients had lower serum UA levels than did healthy individuals. UA levels in ALS were negatively correlated with the rate of disease progression and positively associated with survival, suggesting that UA levels contribute to the progression of ALS. UA levels could be considered a biomarker of disease progression in the early phase in ALS patients.
Amyotrophic Lateral Sclerosis* ; Antioxidants ; Body Mass Index ; Disease Progression ; Hematologic Tests ; Humans ; Kaplan-Meier Estimate ; Oxidative Stress ; Prognosis ; Prospective Studies ; Survival Rate ; Uric Acid*

Objectives: Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. Methods: A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. Results: Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). Conclusions This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.

Objectives: Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. Methods: A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. Results: Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). Conclusions This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.

Type B lactic acidosis is a rare condition in patients with solid tumors or hematological malignancies. Although there have been several theories to explain its mechanism, the exact cause of lactic acidosis remains to be discovered. Lactic acidosis is usually related to increased tumor burden in patients with malignancy. We experienced a case of lactic acidosis in a 39-year-old man who visited an emergency room because of dyspnea, and the cause of lactic acidosis turned out to be recurrent acute leukemia. Chemotherapy relieved the degree of lactic acidosis initially, but as the disease progressed, lactic acidosis became aggravated. Type B lactic acidosis can be a clinical presentation of acute exacerbation of acute leukemia.
Acidosis, Lactic/*diagnosis/etiology ; Acute Disease ; Adult ; Humans ; Leukemia/*complications ; Male

Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 +/- 2.88%) than that of naive NPCCs and NPCCs in small capsule (86.83 +/- 2.32%, 87.67 +/- 2.07%, respectively) at day 7. The viability of naive NPCCs decreased rapidly at day 14 (75.67 +/- 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 +/- 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 +/- 0.09 and 2.13 +/- 0.09) was conserved better compared to that of naive NPCCs (2.04 +/- 0.25 and 1.53 +/- 0.32, respectively) and NPCCs in large capsules (2.04 +/- 0.34 and 1.13 +/- 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion.
Alginates/chemistry/metabolism ; Animals ; Animals, Newborn ; Capsules/chemistry ; Cell Survival ; Diabetes Mellitus/pathology/*therapy ; Disease Models, Animal ; Glucuronic Acid/chemistry/metabolism ; Graft Rejection/etiology/*prevention & control ; Hexuronic Acids/chemistry/metabolism ; Humans ; Insulin/secretion ; Islets of Langerhans/*metabolism/pathology ; Islets of Langerhans Transplantation/*methods ; Postoperative Complications/etiology/*prevention & control ; *Swine

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

5'-AMP-activated protein kinase (AMPK) is a heterotrimeric complex consisting of a catalytic (alpha) and two regulatory (beta and gamma) subunits. Two isoforms are known for catalytic subunit (alpha1, alpha2) and are encoded by different genes. To assess the metabolic effects of AMPKalpha1, we examined the effects of overexpression of adenoviral-mediated AMPKalpha1 in hyperlipidemic type 2 diabetic rats. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an established animal model of type 2 diabetes that exhibits chronic and slowly progressive hyperglycemia and hyperlipidemia. Thirty five-week-old overt type 2 diabetic rats (n=10) were administered intravenously with Ad.AMPKalpha1. AMPK activity was measured by phosphorylation of acetyl CoA carboxlyase (ACC). To investigate the changes of gene expression related glucose and lipid metabolism, quantitative real-time PCR was performed with liver tissues. Overexpression of AMPKalpha1 showed that blood glucose concentration was decreased but that glucose tolerance was not completely recovered on 7th day after treatment. Plasma triglyceride concentration was decreased slightly, and hepatic triglyceride content was markedly reduced by decreasing expression of hepatic lipogenic genes. Overexpression of AMPKalpha1 markedly improved hepatic steatosis and it may have effective role for improving hepatic lipid metabolism in hyperlipidemic state.
Acetyl Coenzyme A ; Adenoviridae ; AMP-Activated Protein Kinases ; Animals ; Blood Glucose ; Catalytic Domain ; Fatty Liver ; Gene Expression ; Glucose ; Hyperglycemia ; Hyperlipidemias ; Lipid Metabolism ; Liver ; Models, Animal ; Phosphorylation ; Plasma ; Protein Isoforms ; Rats ; Real-Time Polymerase Chain Reaction

Fenofibrate is a selective peroxisome proliferator-activated receptor alpha (PPARalpha) activator and is prescribed to treat hyperlipidemia. The mechanism through which PPARalpha agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.
Adiposity ; Animals ; Body Weight ; Cholecystokinin ; Diethylpropion ; Eating ; Epithelial Cells ; Fenofibrate ; Hyperlipidemias ; Ketone Bodies ; PPAR alpha ; Rats ; Rats, Inbred OLETF ; Receptor, Cholecystokinin A ; Receptors, Cholecystokinin

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.