Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery

The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

A Survey of Patients' Thoughts on Anesthesia and Anesthesiologists following Experience with Anesthesia / 대한마취과학회지

BACKGROUND: The image and status of anesthesiology as a medical specialty in the eyes of the general public has been a problem. This study assessed the patients' thoughts on anesthesiologists and their preoperative concerns and examined the influence of any previous anesthetic experience on their apprehension. METHODS: One hundred thirty-nine patients undergoing elective surgical procedures were surveyed with a questionnaire regarding their thoughts on anesthesiologists and their preoperative concerns at preoperative visits. The results were analyzed in terms of a previous experience with anesthesia. RESULTS: Sixty-five patients had previous experience with anesthesia (Group 1), and 74 patients had none (Group 2). Seventy-one percent of patients in Group 1 and 80% in Group 2 reported that a physician-anesthesiologist was in charge of their anesthesia. Regarding the responsibility for the patients' safety during the surgical procedures, 83% of patients in Group 1 and 82% in Group 2 reported that the anesthesiologists were responsible for the patients' well-being. Fifty-seven percent of patients in Group 1 and 58% in Group 2 reported that the anesthesiologists were responsible for their safe recovery from the anesthesia. The most frequent preoperative apprehensions were postoperative pain (57% in Group 1 and 62% in Group 2) and the risk of not waking up from the anesthesia (60% in Group 1 and 57% in Group 2). There were no significant differences between the two groups. CONCLUSIONS: Passive learning from previous anesthetic experience does not affect the patients' thoughts on the anesthesiologists and their preoperative concerns.

The Effect of the Initiating Time of Patient Controlled Analgesia on the Onset of Postoperative Analgesic Effect / 대한마취과학회지

BACKGROUND: Patient controlled analgesia (PCA) is now a widely accepted method of postoperative pain control. It usually begins at postanesthetic care unit, but it takes time to achieve satisfactory level. We have studied the differences in the onset of analgesic effects between starting PCA preoperatively and starting PCA postoperatively. METHODS: Forty patients for subtotal gastrectomy were randomized to two groups. In group I, we started PCA at postanesthetic care unit, in group II, PCA was begun immediately after the induction of anesthesia. We visited each patient and measured 10 cm-visual analgue scale (VAS) score at 3, 6, 9, 12 and 15 hours after the end of operation. We also measured the time taken from the end of operation to extubation. RESULTS: There were no differences in VAS score between two groups on 3 hour. But at 6, 9, and 12 hour, VAS score was significantly lower in group II (P < 0.05). On 15 hour there was no difference between two groups again. There was no significant difference in extubation time between two groups. Preemptive analgesia was not observed in group II. CONCLUSIONS: We concluded that starting PCA immediately after induction of anesthesia can achieve effective analgesia more rapidly than starting PCA at postanesthetic care unit. VAS score was lower than 3 after 12 hours after the end of operation in group II and we speculated that starting PCA 15 hours prior to operation would maximize the analgesic effect of PCA because there was approximately three hours time difference between the two groups.

Tests to Differentiate Cerebrospinal Fluid from Local Anesthetics during Epidural Anesthesia / 대한마취과학회지

BACKGROUND: One of the most serious risks of epidural anesthesia is total spinal blockade from unintentional dural puncture. We evaluated the glucose test and the thiopental precipitation test to differentiate cerebrospinal fluid (CSF) from local anesthetics (LA). METHODS: (1) Experiment 1: CSF from twenty patients was serially diluted with 2% lidocaine or 0.5% bupivacaine. The ratio of CSF to LA-CSF mixture (CSF/(LA+CSF)) was from 0 to 1.0 at an interval of 0.1. We measured the glucose level of each sample with blood sugar meter. (2) Experiment 2: CSF from a hydrocephalus patient was serially diluted and its glucose level of each sample was measured in the same way as Experiment 1. We performed a urine stick test with each sample. Ten anesthetists blinded to the nature of the sample were asked to identify the results of the tests. (3) Experiment 3: Two milimeters of 2.5% thiopental was respectively mixed with local anesthetics, the amount of which was from 0.1 to 1.0 ml at an interval of 0.1 ml. Sixteen anesthetists blinded to the nature of sample were asked to identify the results of the tests. RESULTS: (1) Experiment 1: We can measure glucose level at CSF/(LA +CSF) of 0.5 in 2% lidocaine group and 0.6 in 0.5% bupivacaine group. (2) Experiment 2: We can detect glucose at lower level of CSF/(LA +CSF) by glucose meter than urine stick test (p<0.05). (3) At least 0.35 ml of 2% lidocaine and 0.29 ml of 0.5% bupivacaine was needed respectively to detect precipitation. CONCLUSION: We suggest that blood glucose meter be used instead of glucose test strip. For thiopental precipitation test, we have to adjust the amount of thiopental depending on the amount of test fluid.

Tests to Differentiate Cerebrospinal Fluid from Local Anesthetics during Epidural Anesthesia / 대한마취과학회지

BACKGROUND: One of the most serious risks of epidural anesthesia is total spinal blockade from unintentional dural puncture. We evaluated the glucose test and the thiopental precipitation test to differentiate cerebrospinal fluid (CSF) from local anesthetics (LA). METHODS: (1) Experiment 1: CSF from twenty patients was serially diluted with 2% lidocaine or 0.5% bupivacaine. The ratio of CSF to LA-CSF mixture (CSF/(LA+CSF)) was from 0 to 1.0 at an interval of 0.1. We measured the glucose level of each sample with blood sugar meter. (2) Experiment 2: CSF from a hydrocephalus patient was serially diluted and its glucose level of each sample was measured in the same way as Experiment 1. We performed a urine stick test with each sample. Ten anesthetists blinded to the nature of the sample were asked to identify the results of the tests. (3) Experiment 3: Two milimeters of 2.5% thiopental was respectively mixed with local anesthetics, the amount of which was from 0.1 to 1.0 ml at an interval of 0.1 ml. Sixteen anesthetists blinded to the nature of sample were asked to identify the results of the tests. RESULTS: (1) Experiment 1: We can measure glucose level at CSF/(LA +CSF) of 0.5 in 2% lidocaine group and 0.6 in 0.5% bupivacaine group. (2) Experiment 2: We can detect glucose at lower level of CSF/(LA +CSF) by glucose meter than urine stick test (p<0.05). (3) At least 0.35 ml of 2% lidocaine and 0.29 ml of 0.5% bupivacaine was needed respectively to detect precipitation. CONCLUSION: We suggest that blood glucose meter be used instead of glucose test strip. For thiopental precipitation test, we have to adjust the amount of thiopental depending on the amount of test fluid.

Fiberoptic Bronchoscopy via the Laryngeal Mask Airway: A case report / 대한마취과학회지

The laryngeal mask airway (LMA) has been used with increasing frequency for many purposes. It is one of its advantages that there is no need of muscle relaxants to insert the LMA. So it can be used to look into the movement of glottis during spontaneous respiration. We report a case using a fiberoptic bronchoscope via the laryngeal mask under the impression of cricopharyngeal incoordination. The patient was a 17-days-old and 3.36-kg infant. After injecting glycopyrrolate 0.05mg and propofol 10mg intravenously, a size-1 LMA was inserted. Fiberoptic bronchoscope was inserted through the LMA. We could see the movement of vocal cords normal. Also, no structural abnormality was seen in the larynx and trachea. After removal of the LMA, conventional suspension laryngoscopy was performed to examine the epiglottis and hypopharynx. We could successfully assess the movement and/or structure of vocal cord and trachea. Fiberoptic bronchoscopy via the laryngeal mask airway may be a safe and convinient method in infants.