• The Korean Journal of Pain
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• v.30 no.4
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• pp.272-280
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• 2017

Background: The high cost of intrathecal morphine pump (ITMP) implantation may be the main obstacle to its use. Since July 2014, the Korean national health insurance (NHI) program began paying 50% of the ITMP implantation cost in select refractory chronic pain patients. The aims of this study were to investigate the financial break-even point and patients' satisfaction in patients with ITMP treatment after the initiation of the NHI reimbursement. Methods: We collected data retrospectively or via direct phone calls to patients who underwent ITMP implantation at a single university-based tertiary hospital between July 2014 and May 2016. Pain severity, changes in the morphine equivalent daily dosage (MEDD), any adverse events, and patients' satisfaction were determined. We calculated the financial break-even point of ITMP implantation via investigating the patient's actual medical costs and insurance information. Results: During the studied period, 23 patients received ITMP implantation, and 20 patients were included in our study. Scores on an 11-point numeric rating scale (NRS) for pain were significantly reduced compared to the baseline value (P < 0.001). The MEDD before ITMP implantation was 0.59 [IQR: 0.55-0.82]. The total MEDD increased steadily to 0.77 [IQR: 0.53-1.08] at 1 year, which was 126% of the baseline (P < 0.001). More than a half (60%) responded that the ITMP therapy was somewhat satisfying. The financial break-even point was 28 months for ITMP treatment after the NHI reimbursement policy. Conclusions: ITMP provided effective chronic pain management with improved satisfaction and reasonable financial break-even point of 28 months with 50% financial coverage by NHI program.

• Communications for Statistical Applications and Methods
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• v.18 no.5
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• pp.581-594
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• 2011

The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.

• Journal of Korean Society for Atmospheric Environment
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• v.33 no.2
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• pp.124-138
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• 2017

Physico-chemical measurement of non-refractory submicron particles($NR-PM_1$) was conducted in Baengnyeong Island, Korea using Aerodyne High Resolution Time of Flight Aerosol Mass Spectrometer (HR-ToF-AMS) from 2012 to 2014. Organics and ammoniated sulfate were dominant species in $NR-PM_1$. The organics was found to have similar fractions(approximate 40%) of $NR-PM_1$ during the summer and winter, while the sulfate fractions of $NR-PM_1$ were calculated to be approximately 47% and 31% for the summer and winter, respectively, suggesting the possibility that particles provide non-acidic surfaces for condensation of nitric acid in the winter. The nitrate fractions of approximate 4% and 20% of $NR-PM_1$ were observed in August (summer) and November (winter), respectively, resulting that the relatively low concentration of sulfate in $NR-PM_1$ provided a non-acidic surface for nitric acid condensation and formation of particulate ammoniated nitrate is favored thermodynamically in winter. The new particle formation (NPF) event and particle growth rate were analyzed for each month in 2014 using Scanning Mobility Particle Sizer(SMPS). The Percent of NPF events was the highest in winter, but NPF event was not observed during summer due to relatively high temperature and frequent rainfall. The average particle growth rate was 3.5 nm/h and the highest particle growth rate was 5.5 nm/h in May. We observed the long-range transport of the anthropogenic sulfate from the East Asia during the intensive monitoring period of November between Qingdao and Baengnyeong Island in 2013. The relatively high concentrations of m/z 60 measured in HR-ToF-AMS was observed in May and June at Baengnyeong Island, suggesting the possibility of the influence of biomass burning from the East Asia to the Korean Peninsula.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.146-150
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• 1999

Myasthenia gravis (MG) is relatively rare ouuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150$\~$180 cGy consisting of 10 cGy per fraction, three times a week, for 5~e weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4$\~$6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.9-17
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• 2015

Glycogen storage disease (GSD) type Ia is rare inborn metabolic disorder, caused by glucose-6-phosphatase deficiency. It characterized by hepatomegaly, hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia and it is usually manifested in the infantile period. In addition, it is also associated with growth failure, pubertal delay, anemia, platelet dysfunction, osteopenia, and pulmonary hypertension. Hepatocellular adenoma and renal dysfunction are frequent late complications. Delayed diagnosis and inappropriate therapy lead to many complications such as growth failure, osteoporosis, refractory gout, renal failure, hepatocellular carcinoma (HCC), and pulmonary hypertension. Here, two Korean sisters diagnosed with GSD Ia, aged 33 and 36 respectively, were described and compared to recent articles about four adults with late diagnosis of GSD Ia. One sister had typical manifestations of GSD Ia including short stature (height, 145 cm), multiple hepatic adenoma, chronic kidney disease stage IV, and severe osteoporosis, whereas the older sister had normal stature (162 cm), one tiny hepatic nodule, and normal renal function. Direct sequencing of G6PC in two sisters identified a homozygous splicing mutation, c.645G>T, which is a prevalent mutation in Korea. Interestingly, our cases and four adults from recent reports had asymptomatic mild hypoglycemia and various manifestations including renal failure, HCC, fatty liver, or uncontrolled hyperlipidemia. These adult cases represent not only heterogenous phenotype to genotype within family members with GSD Ia but also long-term complications such as gouty arthritis, renal failure, and osteoporosis in untreated adult GSD Ia patients. In addition, lactic academia and hypertriglyceridemia are good markers of GSD Ia to distinguish from metabolic disease.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.168-172
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• 2003

Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

• International Journal of Oral Biology
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• v.31 no.4
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• pp.113-118
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• 2006

In the primary sensory neuron of the mesencephalic trigeminal nucleus (MTN), the peripheral axon supplies a large number of annulospiral endings surrounding intrafusal fibers encapsulated in single muscle spindles while the central axon sends only a few number of synapses onto single ${\alpha}-motoneurons({\alpha}-MNs)$. Therefore, the ${\alpha}-{\gamma}$ linkage is thought to be very crucial in the jaw-closing movement. Spike activity in a ${\gamma}-motoneuron\;({\gamma}-MN)$ would induce a large number of impulses in single peripheral axons by activating many intrafusal fibers simultaneously, subsequently causing an activation of ${\alpha}-MNs$ in spite of the small number of synapses. Thus, the activity of ${\gamma}-MNs$ may be vital for modulation of jaw-closing movements. Independently of such a spindle activity modulated by ${\gamma}-MNs$, somatic depolarization in MTN neurons is known to trigger the oscillatory spike activity. Nevertheless, the trafficking of these spikes arising from the two distinct sources of MTN neurons is not well understood. In this short review, switching among multiple functional modes of MTN neurons is discussed. Subsequently, it will be discussed which mode can support the ${\alpha}-{\gamma}$ linkage. In our most recent study, simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-back-propagation from the spike-initiation site in the stem axon to the soma in response to a somatic current pulse. The persistent $Na^+$ current was found to be responsible for the spike-initiation in the stem axon, the activation threshold of which was lower than those of soma spikes. Somatic inputs or impulses arising from the sensory ending, whichever trigger spikes in the stem axon first, would be forwarded through the central axon to the target synapse. We also demonstrated that at hyperpolarized membrane potentials, 4-AP-sensitive $K^+$ current ($IK_{4-AP}$) exerts two opposing effects on spikes depending on their origins; the suppression of spike initiation by increasing the apparent electrotonic distance between the soma and the spike-initiation site, and the facilitation of axonal spike invasion at higher frequencies by decreasing the spike duration and the refractory period. Through this mechanism, the spindle activity caused by ${\gamma}-MNs$ would be safely forwarded to ${\alpha}-MNs$. Thus, soma spikes shaped differentially by this $IK_{4-AP}$ depending on their origins would reflect which one of the two inputs was forwarded to the target synapses.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.753-759
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• 2005

Purpose : This study was performed to characterize clinical features of benign convulsions with gastroenteritis(CwG) in infants. Methods : We reviewed clinical features of 67 episodes in 64 patients with afebrile seizure accompanied gastroenteritis admitted to Dept. of Pediatrics Bundang CHA hospital from January 2001 to June 2004. Patients with meningitis, encephalitis/encephalopathy or apparent history of epilepsy were excluded. Results : There were 32 boys and 35 girls. The age of onset ranged from 1 to 42 months($18.5{\pm}6.1$ months). The number of children admitted to the hospital with acute gastroenteritis was 2,887 in the same period. The percentage of patients with CwG was 2.3. Seizure type was exclusively generalized tonic or tonic-clonic seizure. The average number of seizures during a single episode was 3.1 (range, 1-13). Two or more seizures occurred in 53(79.1%) of the 67 episodes. Antiepileptic drugs were administered for 42 episodes. Seizure did not cease after the administration of one kind of antiepileptic drug in 23 episodes(54.7%). The seizures were rather refractory to initial antiepileptic treatment. There were no abnormalities in serum biochemistry test including glucose and electrolytes. Cerebrospinal fluid was normal in all 54 episodes. Stool cultures were negative in 49 episodes. Rotavirus was positive in stools in 51(82.3%) of 62 episodes. Norovirus was positive in stools in 2 episodes and astrovirus in 1 of 18 episodes. CT and/or MRI were performed in 15 cases and demonstrated no neuroradiologic abnormalities. Of 73 Interictal EEG, initial 24 cases showed occasional spike or sharp wave discharges from the mid-line area during stage I-II sleep, which were apparently differentiated from vertex sharp transient or K-complexes. The mean follow-up period was 5.7 months(1-36 months). Three patients experienced a recurrence of CwG, but all patients exhibited normal psychomotor development at the last follow-up. Conclusion : Afebrile infantile convulsions with gastroenteritis are brief generalized seizure in cluster with normal laboratory findings and good prognosis. Therefore CwG is likely to be categorized as situation-related seizure of special syndrome. Recognition of this entity should lead to assurance of the parents and long-term anticonvulsant therapy is not usually warranted.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.611-618
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• 2004

Background : Idiopathic pulmonary fibrosis(IPF), a subtype of IIP(idiopathic interstitial pneumonia), is a fatal disease with a 3-5 year median survival. Many attempts at treating this condition have failed to demonstrate a survival benefit in IPF. Recently Ziesche et $al^{12}$ reported the efficacy of IFN-${\gamma}$ for treating IPF but there is still some controversy. The aim of this study was to determine the efficacy of IFN-${\gamma}$ in patients with advanced IPF who had not been responsive to steroid and cytotoxic agents. Method : Nine patients with advanced IPF(age: $55.4{\pm}15.3$ years, Male: Female=8:1) were enrolled. One year treatment regime with 2 million IU of IFN-${\gamma}$ administered subcutaneously three times a week, and low dose prednisolone(10-30 mg/d) was also used. In the case of a definite aggravation and serious side effects, the IFN-${\gamma}$ was discontinued. During the IFN-${\gamma}$ trial, a pulmonary function test and chest radiography were checked every three month throughout the study. Result : 1) Among 9 patients, only 4 patients were able to complete the 12 month treatment with IFN-${\gamma}$, and 5 patients died during the treatment period. 2) No improvement either in the respiratory symptoms or pulmonary functions were observed any of the patients, even in those who completed the 12 months trial of IFN-${\gamma}$, 3) At the time of IFN-${\gamma}$ trial, the survivors who finished the IFN-${\gamma}$ treatment for 12 months had a higher oxygen level($81.3{\pm}2.8$ vs. $67.4{\pm}8.4$, P=0.024) and a better pulmonary function(FVC: $61.3{\pm}5.1$ % predicted vs. $45.7{\pm}12.3%$, P=0.048, and $D_Lco$: $45.0{\pm}5.0%$ predicted vs. $30.8{\pm}11.2%$, P=0.048) than the non-survivors. Conclusion : Our data suggested that IFN-${\gamma}$ therapy was not effective in the patients with advanced IPF refractory compared with other therapeutic agents. Furthermore, these results suggest that severe impairment of the pulmonary function and hypoxemia during the IFN-${\gamma}$ therapy requires special attention.

• The Korean Journal of Gastroenterology
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• v.72 no.6
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• pp.286-294
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• 2018

Background/Aims: The predictive factors of functional dyspepsia (FD) remain controversial. Therefore, we sought to investigate symptom responses in FD patients after Helicobacter pylori (H. pylori) eradication and used predictive factor analysis to identify significant factors of FD resolution at one-year after commencing eradication therapy. Methods: This prospective, multi-center clinical trial was performed on 65 FD patients that met Rome III criteria and had H. pylori infection. Symptom responses and factors that predicted poor response were determined by analysis one year after commencing H. pylori eradication therapy. Results: A total of 63 patients completed the one-year follow-up. When an eradication success group (n=60) and an eradication failure group (n=3) were compared with respect to FD response rate at one year, results were as follows; complete response 73.3% and 0.0%, satisfactory response 1.7% and 0.0%, partial response 10.0% and 33.3%, and refractory response 15.0% and 66.7%, respectively (p=0.013). Univariate analysis showed persistent H. pylori infection (p=0.021), female gender (p=0.025), and medication for FD during the study period (p=0.013) were associated with poor FD response at one year. However, age, smoking, alcohol consumption, and underlying disease were not found to affect response. Finally, multivariate analysis showed that female gender (OR, 4.70; 95% CI, 1.17-18.88) was the sole independent risk factor of poor FD response at one year after commencing H. pylori eradication therapy. Conclusions: Female gender was found to predict poor response in FD patients despite H. pylori eradication. Furthermore, successful H. pylori eradication appears to be associated with FD improvement, but the number of non-eradicated patients was too small to conclude.