• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.3
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• pp.135-141
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• 2023

Objectives: This study aimed to develop and validate machine learning (ML) models using H₂O-AutoML, an automated ML program, for predicting medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis undergoing tooth extraction or implantation. Patients and Methods: We conducted a retrospective chart review of 340 patients who visited Dankook University Dental Hospital between January 2019 and June 2022 who met the following inclusion criteria: female, age ≥55 years, osteoporosis treated with antiresorptive therapy, and recent dental extraction or implantation. We considered medication administration and duration, demographics, and systemic factors (age and medical history). Local factors, such as surgical method, number of operated teeth, and operation area, were also included. Six algorithms were used to generate the MRONJ prediction model. Results: Gradient boosting demonstrated the best diagnostic accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.8283. Validation with the test dataset yielded a stable AUC of 0.7526. Variable importance analysis identified duration of medication as the most important variable, followed by age, number of teeth operated, and operation site. Conclusion: ML models can help predict MRONJ occurrence in patients with osteoporosis undergoing tooth extraction or implantation based on questionnaire data acquired at the first visit.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.16-26
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• 2023

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.474-482
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• 1993

Background: As a physiologic plasminogen activator, tissue-type plasminogen activator (t-PA) could induce effective thrombolysis in massive pulmonary embolism, without the risk of systemic hemorrhage. However, therapeutic doses of t-PA has been associated with systemic lytic state, and fibrin selectivity may be influenced by the dosing regimen of t-PA. To investigate the effects of duration of t-PA infusion on blood coagulation system, we performed this study. Method: In a canine model of pulmonary embolism, which was induced by injection of autologous blood clots, we administered equal doses of t-PA (1 mg/kg) over 15 minutes in $t-PA_{15}$ group, over 180 minutes in $t-PA_{180}$ group, and only saline in control group. Then serial blood samplings were made to check complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin, plasminogen, ${\alpha}_2$-antiplasmin, coagulation factor V and VIII, and fibrin(ogen) degradation products. Results: 1) In all 3 groups, complete blood count showed same changes. Hemoglobin, hematocrit and platelet count decreased, but WBC count increased. 2) Prothrombin time, activated partial thromboplastin time, and thrombin time were prolonged during 15-60 minutes after t-PA administration in $t-PA_{15}$ group, and from 30 minutes through 180 minutes after administration in $t-PA_{180}$ gorup. 3) Fibrin, ${\alpha}_2$-antiplasmin, and cogulation factor V and VIII decreased in both $t-PA_{15}$ and $t-PA_{180}$ group, but returned to basal levels earlier in $t-PA_{15}$ group. 4) Fibrin(ogen) degradation products increased after pulmonary embolism in all groups, and further increased in both $t-PA_{15}$ and $t-PA_{180}$ groups after t-PA infusion. But more pronounced increment was noted in $t-PA_{180}$ gorup. Conclusion: In pulmonary embolism, the shorter (15 minutes) infusion of t-PA would have less risk of systemic hemorrhage than the longer (180 minutes) infusion when the doses is equal. And, this suggests that manipulating the duration of t-PA infusion can reduce the risk of major bleeding.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.51-57
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• 2006

Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.613-620
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• 1999

Background: Recently, regional or isolated organ perfusion is being studied again as a drug administration modality which is able to reduce systemic toxicity while delivering high-dose chemotherapeutic agents. This research was planned to evaluate the pharmacokinetics and long-term pathologic changes of the lung in isolated lung perfusion (ILP) with cisplatin. Material and Method: Twenty-five New Zealand white rabbits were divided into 2 groups (Group I: 10, Group II: 15). The groups were then subdivided into 2 and 3 subgroups of 5 rabbits. In group I, tissue samples of the lung and kidney, and systemic blood for platinum concentration measurement were taken 30 minutes after systemic intravenous infusion of cisplatin (5 mg/kg) and isolated lung perfusion in each 5 rabbits. In 2 subgroups of group II, lung tissues for pathologic exams were taken 30 minutes and 1 week after ILP in each 5 rabbits, which received 10% pentastarch solution only and cisplatin, respectively. In the other subgroups, lung biopsy was undertaken 4 weeks after ILP with cisplatin. Result: When cisplatin was infused via systemic vein, the platinum concentration in the lung, kidney and plasma were 1.50${\pm}$0.43 $\mu\textrm{g}$/g, 7.65${\pm}$2.49 $\mu\textrm{g}$/g, 1.19${\pm}$0.03 $\mu\textrm{g}$/ml, respectively. However, the platinum concentration in the lung was about 50 times higher (75.43${\pm}$11.47 $\mu\textrm{g}$/g) than that of intravenous infusion group, and those in the kidney and plasma were decreased (1.30${\pm}$ 0.35 $\mu\textrm{g}$/g, 0.13${\pm}$0.02 $\mu\textrm{g}$/ml) when cisplatin was introduced through ILP. Pathologic change in the treated lung with ILP was characterized by the medial hypertrophy of the pulmonary arterioles and interstitial eosinophilic infiltration, which was not dependent on cisplatin

• Journal of Chest Surgery
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• v.29 no.2
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• pp.191-198
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• 1996

Amrinone is a non-glycosidic, non-adrenergic positive inotropic agent with peripheral and coronary vasodilator effect. It inhibits phosphodiesterase F-III, the cardiac cyclic-AMP specific phosphodiesterase, selectively and potently. In this study, the effects of IV administered amrinone and dopamine were compared in 40 patients who had open heart surgery. Amrinone was administered as a bolus of 1 5~2mglkg for several minutes, followed by continuous infusion at 5~1 Oug/kg/min. The hemodynamic measurements including heart rate, systolic and diastolic pressure, cardiac index, pulmonary wedge pressure, and systemic vascular resistance were recorded immediately for 12~24 hours awl 7th day following operation. In amrinone group, cardiac index increased from 3.73$\pm$1.39 L/min/m2 to 5.44$\pm$2.65 L/min/m2 at the time of posterative 48 hours (n=20, p< 0.05). The decrease in systemic vascular resistance from 1237.5 $\pm$ 637.7 dyne/sec/cm2 to 1000.8 $\pm$ 608.5 dyne/sec/cm2(p<0.05). In Dopamine group, the heart rate increased from 92.1 $\pm$ 13.0/min to 101.0 $\pm$ 13.1/min and the cardiac index decreased from 3.40 $\pm$ 0.50 L/min/m2 to 2.53 $\pm$ 1.15 L/min/m2 at the time of postoperative 12 hours(p<0.05). Systemic vascular resistance increased from 1058.5 $\pm$ 234.6 dyne/sec/cm2 to 1979.7 $\pm$ 759.2 dynelsec/cm2 The comparison of the hemodynamic effects of amrinone and dopamine, both drugs improved cardiac performance. But the administration of amrinone results in a higher cardiac index, diastolic blood pressure and lower systemic vascular resistance than those achieved with dopamine (p<0.05). The uniqueness of the action of amrinone on the heart and its sustained hemodynamic effect suggest it has clinical promise, pos operative care of cardiac surgery

• Journal of Oral Medicine and Pain
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• v.37 no.3
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• pp.161-167
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• 2012

Burning mouth syndrome(BMS) is defined as chronic, painful burning sensation in the oral mucosa. Treatments for BMS include medication and psychiatric interventions. Capsaicin, alpha-lipoic acid, and topical and systemic clonazepam showed more effective in reducing the symptoms of BMS in the previous studies. The purpose of this study is to evaluate of the therapeutic efficacy of systemic clonazepam in BMS and to elucidate the relationships between such a efficacy and various clinical features, including age, pain intensity, pain duration, previous dental history and condition of oral mucosa. A retrospective clinical records audit was performed of patients diagnosed with BMS between January 2011 and August 2012. Patients were prescribed 0.5 mg clonazepam two times daily. Pain was assessed by patients on an 11-point numeric rating scale (NRS; 0 to 10) before and 1-2 weeks after systemic administration of clonazepam. The efficacy of clonazepam was evaluated in terms of patient's age, initial pain intensity, pain duration, presence or absence of precipitating event, condition of the tongue, presence or absence of denture. A total of 50 patients (46 women, 4 men) were included in this study. The patients were divided into two or three groups according to above clinical features. The amount of mean NRS reduction in patients with severe initial pain was $3.33{\pm}2.74$, whereas that in patients with mild initial pain was $1.64{\pm}1.54$. The amount of mean NRS reduction in oldest patients was $3.53{\pm}1.94$ (${\geq}$70yrs), and those in another younger patients were $2.88{\pm}1.80$(< 60yrs) and $1.54{\pm}2.86$(60yrs ${\leq}$ age < 70yrs), respectively. It was concluded that the older patients and the patients with higher intensity of initial pain tend to show better efficacy of clonazepam. However, There were no statistically significant differences according to pain duration, presence or absence of precipitating events, tongue fissuring, and wearing dentures.

• Clinical and Experimental Pediatrics
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• v.63 no.7
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• pp.265-271
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• 2020

Background: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates. Purpose: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants. Methods: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group. Results: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 ㎍/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 ㎍/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). Conclusion: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.231-243
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• 1988

This study was performed to investigate the mechanism of changes in arterial blood pressure, as a typical example of somatosympathetic reflex, induced by activation of muscular afferent nerves. Cats were anesthetized with ${\alpha}-chloraloae$ (60 mg/kg, i.p.). Afferent fibers in muscle nerve were activated by various method muscle contraction, electrical stimulation of muscle nerves, intraarterial injection of some algesic substances and noxious mechanical stimulation etc-and the evoked changes in arterial blood pressure were monitored. The effects of intravenous or direct spinal administration of morphine on the changes in arterial blood pressure induced by activation of the muscle afferent fibers were observed and also the effects of spinal lesions made in the $L1{\sim}L3$ spinal cord on them were studied to identify the ascending spinal pathways of the somatosympathetic reflexes. Followings are the results obtained. 1) The stimulation of medial gastrocnemius nerve under non-paralyzed condition with C-strength, low frequency (lower than 20 Hz) stimuli elicited a depressor response and a pressor response was elicited with C-strength, high frequency stimuli, of which the maximal response was observed at 100 Hz stimulation. 2) When the animal was paralyzed, depressor response to stimulation of the medial gastrocnemius nerve was observed with C-strength, $0.5{\sim}5Hz$ stimuli although the amplitude of the depressor response was decreased. The maximal pressor response was observed during stimulation with C-strength, $20{\sim}100Hz$ stimuli. 3) Intraarterial injection of some algesic substances induced marked pressor responses while noxious mechanical stimulation of the medial gastrocnemius muscle was not enough to elicit any significant changes (larger than 10 mmHg) in arterial blood pressure. 4) Systemically administered morphine (2 mg/kg) lowered the arterial blood pressure immediately and persistently and it was reversed by administration of naloxone. Direct spinally administered morphine did not elicit any changes. 5) The pressor response elicited by the activation of muscle afferent nerves was strengthened by systemic morphine administration while the depressor response tended to decrease. 6) Morphine administered on the spinal cord directly, decreased pressor response but did not change depressor response. From the above results it is concluded that there are separate groups of afferent nerves in the medial gastrocnemius nerve, which elicit pressor and depressor responses and the spinal ascending pathways of them are also separated from each other.