• IMMUNE NETWORK
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• v.20 no.1
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• pp.8.1-8.15
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• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• Archives of Obesity and Metabolism
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• v.3 no.1
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• pp.27-34
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• 2024

The prevalence of obesity in children and adolescents is increasing worldwide. Obesity in children and adolescents not only increases the risk of transitioning to obesity in adulthood but also increases the risk of cardiometabolic diseases such as high blood glucose, high blood pressure, dyslipidemia, fatty liver, and hyperinsulinemia during childhood. The goal of treating obesity in children and adolescents is not to focus on weight loss but to help children reach a healthy weight while maintaining normal growth appropriate for their age and sex. To achieve this goal, regular physical activity and exercise, dietary modification, improvement of obesity-prone environmental factors, and behavioral changes are required for a healthy lifestyle. If appropriate weight control is not achieved through lifestyle modifications, pharmacotherapy may be considered for adolescents with severe obesity aged 12 and above. Recent clinical trials have reported the efficacy and safety of pharmacotherapy in severely obese adolescents. Currently, two medications can be prescribed in Korea for patients with obesity aged 12 and above: Orlistat and Liraglutide. However, despite effective weight control through drug treatment, body weight may increase again after treatment discontinuation. Therefore, it is crucial to evaluate adherence to health behaviors during visits and continue to educate on lifestyle modifications, even during pharmacotherapy, to minimize weight regain.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• The Journal of Internal Korean Medicine
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• v.44 no.4
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• pp.751-756
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• 2023

Objective: This study attempts to increase awareness of hepatotoxicity caused by antipsychotic drugs and to provide updated information on drug-induced liver injury (DILI) to physicians in Korean medicine (KM) clinics. Methods: This study presents a detailed case of a female patient diagnosed with DILI attributed to antipsychotic drugs, highlighting the improvement observed through laboratory findings. Results: A 56-year-old female patient with underlying disorders, including mixed connective tissue disease and depression, was under medical care. One day, she reported experiencing intense fatigue and distressing sensations, prompting the author to order blood tests. The levels of AST and ALT were significantly elevated by more than 2.5-fold, indicating hepatocellular DILI. The RUCAM score for antipsychotic drugs was 9, as no other medications, including herbal medicine, were being taken. Upon discontinuation of the antipsychotic drugs, the patient's laboratory findings returned to normal levels within 2 weeks, accompanied by a recovery of subjective symptoms. Conclusion: This study presents a noteworthy case of hepatotoxicity caused by antipsychotic drugs, serving as an illustrative example that highlights the crucial need for awareness among doctors of KM in clinical settings.

• Tuberculosis and Respiratory Diseases
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• v.78 no.4
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• pp.321-325
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• 2015

Background: The adverse effects of the phosphodiesterase-4 inhibitor roflumilast, appear to be more frequent in clinical practice than what was observed in chronic obstructive pulmonary disease (COPD) clinical trials. Thus, we designed this study to determine whether adverse effects could be reduced by starting roflumilast at half the dose, and then increasing a few weeks later to $500{\mu}g$ daily. Methods: We retrospectively investigated 85 patients with COPD who had taken either $500{\mu}g$ roflumilast, or a starting dose of $250{\mu}g$ and then increased to $500{\mu}g$. We analyzed all adverse events and assessed differences between patients who continued taking the drug after dose escalation and those who had stopped. Results: Adverse events were reported by 22 of the 85 patients (25.9%). The most common adverse event was diarrhea (10.6%). Of the 52 patients who had increased from a starting dose of $250{\mu}g$ roflumilast to $500{\mu}g$, 43 (82.7%) successfully maintained the $500{\mu}g$ roflumilast dose. No difference in factors likely to affect the risk of adverse effects, was detected between the dose-escalated and the discontinued groups. Of the 26 patients who started with the $500{\mu}g$ roflumilast regimen, seven (26.9%) discontinued because of adverse effects. There was no statistically significant difference in discontinuation rate between the dose-escalated and the control groups (p=0.22). Conclusion: Escalating the roflumilast dose may reduce treatment-related adverse effects and improve tolerance to the full dose. This study suggests that the dose-escalated regimen reduced the rate of discontinuation. However, longer-term and larger-scale studies are needed to support the full benefit of a dose escalation strategy.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

• The Korean Journal of Nuclear Medicine
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• v.20 no.2
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• pp.85-100
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• 1986

To evaluate the clinical and pathogenetic roles of TSH receptor antibodies in autoimmune thyroid diseases, TBII were measured by TSH-radioreceptor assay methods in 352 patients with Graves' disease, 108 patients with other thyroid diseases and 69 normal persons. The normal range of TBII activity was less than 15%. The frequencies of detectable TBII in 169 patients with untreated Graves' disease, 31 patients with hyperthyroidism under treatment and 70 patients with euthyrodism under treatment were 92.4%, 87.1% and 54.3% respectively. However 12 (21.8%) out of 55 patients who have been in remission more than one year after discontinuation of antithyroid drugs treatment had detectable TBII activities in their sera. In 196 patients with untreated Graves' disease, the frequency of TBII increased by increasing size of goiter and the frequency of proptosis was significantly high in patients whose TBII activities were more than 60%. TBII activities were roughly correlated with total $T_3,\;T_4$ and free $T_4$ index but low $\gamma^2$ value(less than 0.1). In 67 patients with Graves' disease who were positive TBII before antithyroid drugs treatment, TBII activities began to decrease from the third months and it was converted to negative in 35.8% of patients at 12 months after treatment. There were no significant differences of the declining and disappearing rates of TBII activities between high dose and conventional dose groups. TBII activities were significantly increased initially (2-4 months) and then began to decrease from 5-9 months after $^{131}I$ treatment. There were two groups, one whose TBII activities decreased gradually and the other did not change untill 12 months after subtotal thyroidectomy. Although preoperative clinical and laboratory findings of both groups were not different, TBII activities of non-decreasing group were significantly higher than those of decreasing group$(74.6{\pm}18.6%\;vs\;39.2{\pm}15.2%;\;P<0.01)$. Thirty three(55.9%) out of 59 patients with Graves' disease relapsed within 1 year after discontinuation of antithyroid drugs. The positive rate of TBII at the end of antithyroid drug treatment in relapse group(n=33) was significantly higher than those in remission group (n=26) (63.6% vs 23.1%; P < 0.05). The mean value of TBII activities at the end of antithyroid drug treatment in relapse group was significantly elevated $(29.7{\pm}21.4%\;vs\;14.7{\pm}11.1%,\;P<0.05)$. Positive predictive value of TBII for relapse was 77.8%, which was not different from those of TRH nonresponsiveness(78.6%). The frequencies of detectable TBII in 68 patients with Hashimoto's thyroiditis, 10 patients with painless thyroiditis and 5 patients subacute thyroiditis were 14.7%, 20% and 0%, respectively. However in 25 patients with primary nongoitrous myxedema, 11 patients(44%) showed TBII activities in their sera. 9 out of 11 patients who had TBII activities in their sera showed high TBII activities(more than 70% binding inhibition) and their IgG concentrations showing 50% binding inhibition of $^{125}I-bTSH$ to the TSH receptor were ranges of 0.1-2.6 mg/dl. One patient who had high titer of TBII in her serum delivered a hypothyroid baby due to transplacental transfer of maternal TBII. These findings suggested that 1) TSH receptor antibodies are closely related to a pathogenetic factor of Graves' hyperthyroidism and of some patients with primary non-goitrous myxedema, 2) measurement of TSH receptor antibodies is helpful in evaluating the clinical outcome of patients with Graves' disease during antithyroid drug treatment and in predicting the neonatal transient hypothyroidism of baby delivered from primary myxedema patients. 3) there are 2 or more different types of TSH receptor antibodies in autoimmune thyroid diseases including one which stimulates thyroid by binding to the TSH receptor and another which blocks adenylate cyclase stimulation by TSH.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.571-576
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• 2018

Background: Korean Red Ginseng (KRG) has been used in Asia for its various biological effects, but no studies have investigated the safety of its long-term intake. Therefore, the present study evaluated the safety of KRG intake for 24 weeks. Methods: We randomized 1,000 participants in a 1:1 ratio into two groups, which were treated daily with 2 g of KRG or a placebo for 24 weeks. The primary endpoint was all adverse events and adverse drug reactions (ADRs) that occurred after KRG or placebo administration, which were reported at week 4, 12, and 24 after the baseline visit. Results: In total, 192 and 211 participants experienced adverse events in the KRG and placebo groups (39.2% and 42.0%, respectively; p = 0.361), and 59 and 57 KRG- and placebo-treated individuals reported ADRs (12.0% and 11.4%, respectively; p = 0.737). The frequently occurring ADRs were pruritus (2.0%), headache (1.6%), diarrhea (1.4%), and dizziness (1.2%) in the KRG group and pruritus (2.0%), headache (1.8%), dizziness (1.6%), rash (1.4%), and diarrhea (1.2%) in the placebo group. Discontinuation of drug administration due to ADRs was reported in 13 participants, six (1.2%) and seven (1.4%) in the KRG and placebo groups, respectively (p = 0.814). No significant abnormal changes were revealed by anthropometric, laboratory, and vital sign measurements in the KRG group compared with those in the placebo group. Conclusion: The present study confirms the safety and tolerability of daily intake of 2 g of KRG for 24 weeks by healthy adults.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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• pp.141-146
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• 2003

Objective:To find out the optimal assessment that can relieve amenorrhea associated with risperidone. Methods:Sixteen female outpatients who have taken risperidone for more than 3 months reported voluntarily amenorrhea during Nov 2001 to May 2002. Since the reports of the amenorrhea, the resolution of amenorrhea has been prospectively followed during the next six months. The dosage of risperidone was reduced or discontinued in nine of sixteen patients, while risperidone was switched to olanzapine or quetiapine in other 7 patients according to the clinician's decision. Results:Fourteen of 16 patients showed higher levels of prolactin than normal level. Five patients of the risperidone-reduction group recovered from the amenorrhea while all subjects of the drug-switch group recovered. The resolved patients of the former group recovered from amenorrhea in the dosage below 3mg per day of risperidone. Two patients of the risperidone-reduction group were dropped out during the reduction. Conclusion:These findings suggest that risperidone-induced amenorrhea may be alleviated by reducing dosage to less 3mg per day(including discontinuation) or by switching to other antipsychotic drugs. Whether we would choose which method depends on patient's clinical status, diagnosis, and dose of medication and so on.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.126-128
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• 2012

We report on a case of severe hepatotoxicity in a 52-year-old male with multiple myeloma (MM) who had received bortezomib therapy. At patient presentation, liver enzymes were normal, but started to markedly increase 3 days after the patient's second dose of bortezomib was administered, when free kappa light chains were noticeably reduced in the serum. After discontinuation of bortezomib, liver enzymes recovered gradually to baseline. Then, the patient was started on a thalidomide-containing regimen, which he was able to tolerate well. The patient achieved complete remission prior to autologous stem cell transplantation (ASCT). The patient underwent ASCT without occurrence of further liver toxicity.