Current Stimulator IC for Retinal Prosthesis Using Nanowire FET Switch Array and in vitro Experiment with rd1 Mouse

학위논문 (석사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2015. 2. 조동일.망막 색소 변성 (Retinitis pigmentosa) 및 노인성 황반 변성 (Age-related macular degeneration) 은 난치성 망막 변성 질환으로서 발병 후 수 년 내에 시력을 완전히 상실하게 한다. 이러한 망막 변성 질환을 치료하기 위해 전기 자극으로 시각 신경 신호를 발생시키는 인공망막 장치가 개발되어 왔다. 최근에는 세계 각지의 연구 그룹에서 자극 해상도를 1,000 픽셀 이상으로 높여 보다 뚜렷한 시각 정보를 전달하려는 시도를 하고 있다. 그러나 기존의 one-to-one interconnection 방식으로 전극과 자극기 회로를 연결할 경우, 배선이 복잡해져 유연한 인공망막 장치를 개발하기 어렵다. 이에 따라 본 연구진에서는 32 × 32 픽셀의 나노와이어 field-effect transistor (FET) 스위치 array 를 이용하여 배선의 복잡성을 줄인 고해상도 인공망막 장치를 개발하고 있다. 본 논문에서는 나노와이어 FET 스위치 기반의 인공망막 자극기 구동을 위한 자극기 회로에 대해 다루고 있다. 본 자극기 회로는 12 V 의 자극 전압을 사용하여, 0 ~ 100 μA 의 자극 전류를 주입할 수 있도록 설계하였다. 또한 나노와이어 FET 스위치 기반의 인공망막 자극 시스템 구동을 위한 디지털 인터페이스 회로를 포함하고 있다. 본 자극기 회로는 12 V 의 고전압 자극을 인가하기 위해 0.35 μm bipolar-CMOS (Complementary Metal-Oxide-Semiconductor)-DMOS (Double Diffused Metal-Oxide-Semiconductor) 공정을 이용하여 제작하였다. 자극기 회로의 기능 검증을 위해 전류 주입 실험 및 in vitro 실험을 진행하였다. 전류 주입 실험 결과 입력 신호에 따라 자극 전류의 세기가 적절히 변화하였으며, 시뮬레이션과 5% 내외의 오차를 보였다. 또한 in vitro 실험을 통해 전류 자극 세기에 따라 신경 반응이 조절되는 유효한 신경 자극을 인가할 수 있음을 확인하였다.Retina pigmentosa (RP) and Age-related macular degeneration (ARMD) are incurable retinal degenerative diseases that cause vision loss in several years after disease onset. Retinal prosthetic devices using electrical stimulations have been developed to restore vision of people blinded from the RP and ARMD. Recently, many research efforts have been tried to achieve a high-spatial resolution with more than 1,000 pixels. However, it is difficult to achieve the high-spatial resolution with the conventional one-to-one interconnection method that requires excessive wiring complexities. In our research group, a high-resolution retinal prosthetic system using a nanowire field-effect transistor (FET) switch integrated 32 × 32 microelectrode array (MEA) has been developed to resolve the wiring problem. In this paper, a current stimulator integrated circuit (IC) to operate the nanowire FET switch integrated MEA is presented. The stimulator circuit generates a biphasic stimulation current in a range of 0 to 100 μA using a high stimulation voltage of 12 V. The digital interface circuits are also integrated in the stimulator IC to operate the MEA. For the high voltage stimulation of 12 V, the stimulator IC is fabricated using a 0.35 μm bipolar-CMOS (Complementary Metal-Oxid-Semiconductor)-DMOS (Double Diffused Metal-Oxide-Semiconductor) process. Experimental results show that the amplitude of the stimulation current is properly modulated according to the level of the input signal. Errors between the measured current amplitudes and the simulated levels are approximately 5%. An in vitro experiment is also conducted to evaluate the neural stimulating function of the fabricated stimulator IC. In the in vitro experiment, the neural responses are successfully evoked by the current stimulation from the stimulator IC.제 1 장 서 론 1 제 1 절 연구의 배경 1 제 1 항 망막 변성 질환 1 제 2 항 시각 보철의 종류 5 제 3 항 인공망막 장치의 분류 7 제 4 항 인공망막 장치 연구 동향 12 제 5 항 고해상도 인공망막 자극기 개발의 필요성 15 제 6 항 고해상도 자극을 위한 나노와이어 FET 스위치 array 기반 인공망막 자극 시스템 17 제 2 장 본 론 19 제 1 절 설계 개념 19 제 1 항 나노와이어 FET 스위치 array 기반 인공망막 자극 시스템의 동작 개념 19 제 2 항 나노와이어 FET 스위치 array 기반 인공망막 자극기 회로의 동작 조건 21 제 2 절 설계 및 시뮬레이션 25 제 1 항 자극기 회로 전체 구성 25 제 2 항 Analog block 설계 27 제 3 항 Digital block 설계 36 제 4 항 Layout 43 제 3 절 시스템 구현 45 제 1 항 자극 시스템 구현을 위한 PCB 제작 45 제 4 절 실험 및 검증 48 제 1 항 전기적 특성 평가 48 제 2 항 in vitro 동물 실험 56 제 3 장 결 론 65 제 1 절 자극기 회로의 기능성 평가 65 제 2 절 향후 계획 67 참고문헌 68 ABSTRACT 74Maste

Neutropenic Enterocolitis in Acute Myelogenous Leukemia

Neutropenic enterocolitis is an acute life-threatening, necrotizing inflammation of cecum and terminal ileum often seen in leukemia and lymphoma during periods of prolonged or severe neutropenia. It has been also referred to as necrotizing enterocolitis, ileocecal syndrome, or typhlitis (from the Greek word typhlon meaning cecum). The pathophysiology of the neutropenic enterocolitis is unknown but is believed to be multifactorial. The clinical symptoms of neutropenic enterocolitis are nonspecific including fever, abdominal pain (often right lower quadrant), abdominal distension, diarrhea, bloody stools, nausea, and vomiting. So acute appendicitis is should be included in the differential diagnosis. The early signs and symptoms are nonspecific and it may rapidly lead to intestinal perforation. The definite management of neutropenic enterocolitis is contrversial. but the prognosis is likely to be good with early diagnosis and proper management. We report one case of neutropenic enterocolitis in acute myelogenous leukemia with literature review.ope

국소적 진행성 상부위암에서 비장보존 림프절 절제술이 수술결과에 미치는 영향

Dept. of Medicine/석사Background: The aim of this study was to investigate the effects of D2 lymphadenectomy with spleen preservation on surgical outcomes in locally advanced proximal gastric cancer. Methods: Between January 2000 and December 2004, a total of 366 patients who underwent curative total gastrectomy were studied retrospectively from a prospectively-designed database. Results: The spleen-preservation group experienced shorter operation times, a lower incidence of perioperative transfusion, and shorter postoperative hospital stays. Perioperative transfusion and splenectomy were independent risk factors for morbidity. There was no significant difference between the two groups in recurrence or cumulative survival rate when adjusted according to cancer stage. Multivariate analysis showed that tumor size, serosal invasion, and nodal metastasis were independent prognostic factors, while splenectomy was not. The cumulative survival rate in pN0-status patients was significantly higher in the spleen-preservation group, while there was no significant difference in the survival of pN1- or pN2-status patients between the two groups. Conclusions: Splenectomy for lymph node dissection in proximal gastric cancer patients obviously showed poor short surgical outcomes, but it did not affect long-term outcomes in terms of recurrence and overall survival rate. Therefore, spleen-preserving lymphadenectomy is a feasible method for radical surgery in locally advanced proximal gastric cancer.ope

On Stability of minimal surface

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Macroscopic Borrmann type as a simple prognostic indicator in patients with advanced gastric cancer

BACKGROUND: The purpose of this study was to clarify the clinical significance of macroscopic Borrmann type in advanced gastric cancer. METHODS: From 1987 to 2001, we retrospectively studied the clinicopathological features and prognoses of 3,966 patients with advanced gastric cancer according to the macroscopic classification of Borrmann type. RESULTS: Multivariate analysis showed that gender, Borrmann type and depth of invasion were all associated with the status of nodal involvement. There were statistically significant differences in overall survival among patients with Borrmann type I and II tumors, Borrmann type III tumors, and Borrmann type IV tumors according to depth of invasion (pT) and nodal involvement (pN), except in pN3 tumors. Borrmann type was an independent prognostic factor in patients with advanced gastric cancer. Furthermore, the 5-year survival rates of patients with Borrmann type III and type IV tumors after curative resection were 62.0 and 51.2%, respectively; this was significantly higher than after noncurative resection (17.8 and 18.0%, respectively). CONCLUSION: Macroscopic Borrmann type is a simple and valuable predictor for lymph node metastasis and survival in advanced gastric cancer patients.ope

Risk factors of survival and surgical treatment for advanced gastric cancer with large tumor size

BACKGROUND: The purpose of this study was to clarify the clinical significance of tumor size in advanced gastric cancer and to evaluate the risk factors of survival in advanced gastric cancer with large tumor size. METHODS: The cut-off point for tumor size, 90th percentile value of tumor size in advanced gastric cancer, was determined to be 10 cm. We retrospectively studied the clinicopathological features and prognosis of 406 patients with advanced gastric tumors measuring 10 cm or more. RESULTS: Large tumors had a propensity for the following: Borrmann type IV, adjacent organ invasion, lymph node and distant metastasis, and stage IV classification. Tumor size was an independent risk factor for lymph node metastasis and survival in advanced gastric cancer. In patients with large advanced gastric cancer, Borrmann type IV, adjacent organ invasion, and N2-3 nodal involvement were independent factors associated with a poorer prognosis. The 5-year survival rate in large gastric cancer patients without any risk factors (65.5%) was similar with those in small gastric cancer patients (59.3%, P = 0.123). CONCLUSION: Tumor size was a simple predictor for lymph node metastasis and survival in advanced gastric cancer. Radical surgery should be recommended for large advanced gastric cancer patients without risk factors, while large gastric cancer with risk factors may not be a surgically treatable disease.ope

Efficacy of Intravenous Iron Sucrose for Treating Anemia after Gastrectomy

Purpose: Many patients suffer with anemia after gastrectomy. Iron deficiency due to a decreased oral intake and malabsoption is the most common cause of anemia in gastrectomized patients. This study evaluated the efficacy of administering intravenous iron sucrose for treating patients with anemia. Materials and Methods: From May 2007 to October 2007 at Yonsei University Severance Hospital, we reviewed 47 outpatients whose hemoglobin levels were below 11 g/dl after gastrectomy. Iron sucrose was used for iron supplementation. To determine the difference between before and after the treatment (at 1 week, 2 weeks, 3 weeks, 3 months and 6 months after treatment), we prospectively examined such anemia parameters as the hemoglobin level (Hgb), the hematocrit (Hct), serum iron, TIBC, ferritin and transferin. Results: Out of the 47 patients, only 36 completed their treatment. Eleven were male and 25 were female. The Hgb levels, which indicate anemia, were elevated 0.6, 0.8, 1.3, 2.1 and 2.2 g/dl after 1 week, 2 weeks, 3 weeks, 3 months and 6 months after administration, respectively (P<0.001). The changes from 1 week to 3 months were statistically significant, but those from 3 to 6 months were not. The Hgb levels of 26 patients, which accounted for 72% of all the patients, elevated up to 12 g/dl or more. No side effects or complications were found, but there was one case of temporary nausea. Conclusion: Anemia after gastrectomy is safely treated in a relatively short time with administering iron sucrose. The patients' Hgb levels are expected to increase in a week and keep increasing up to 3 monthsope

Risk factors for lymph node metastasis in undifferentiated early gastric cancer.

BACKGROUND: Endoscopic surgery has not been accepted as a curative treatment for intramucosal undifferentiated early gastric cancer (EGC). The purpose of this study was to evaluate the predictive factors of lymph node metastasis and explore the possibility of using endoscopic surgery for undifferentiated EGC. METHODS: We retrospectively analyzed 646 patients with undifferentiated EGC who had undergone gastrectomy with D2 lymphadenectomy from January 2000 to March 2005. We used univariate and multivariate analysis to identify clinicopathological features that were predictive factors for lymph node metastasis. RESULTS: The incidence of lymph node metastasis was 4.2% in intramucosal and 15.9% in submucosal undifferentiated EGC. Multivariate analysis revealed that submucosal invasion, larger tumor size (greater than 2 cm), and presence of lymphovascular invasion (LVI), were significantly associated with lymph node metastasis in patients with undifferentiated EGC. Tumor size and LVI were independent risk factors for lymph node metastasis in cases of intramucosal EGC. Lymph node metastasis was found in only one patient (0.5%) who had neither of the two risk factors for intramucosal EGC. CONCLUSION: Complete endoscopic resection may be acceptable as a curative treatment for intramucosal undifferentiated EGC when the tumor size is less than or equal to 2 cm, and when LVI is absent in the postoperative histological examination. Radical gastrectomy should be recommended if LVI or unexpected submucosal invasion is presentope