• 한국임상약학회지
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• 제32권2호
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• pp.67-73
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• 2022

Objectives: Hyponatremia is prevalent electrolyte disorder and can be fatal in older adults. Evaluative studies on hyponatremia among older adults are scarce, especially targeting for those who visited emergency department (ED). We aimed to estimate the prevalence and to identify risk factors of hyponatremia among elderly patients visiting the ED. Methods: A retrospective chart review was completed including 65 or older patients who visited ED at Seoul National University Bundang Hospital from September to December 2019. Patients with the serum sodium concentration of less than 130mEq/L was defined as a hyponatremia group. Logistic regression analysis was conducted to assess predictive factors for hyponatremia. Results: Of the total 2,445 patients, 155 (6.3%) were confirmed to have hyponatremia at the time of ED visits. Risk factors for hyponatremia identified in logistic regression analysis were thiazides (aOR=2.64, 95% CI 1.66-4.21), opioids (exclude tramadol) (aOR=3.45, 95% CI 1.72-6.94), and desmopressin (aOR=6.98, 95% CI 2.45-19.84). Compared to the use of thiazides alone, it was confirmed that the possibility of hyponatremia was more than quadrupled when proton pump inhibitor (PPI) was used together (aOR=4.08, 95% CI 1.74-9.55). Conclusions: About 6.3% of older adults visiting the ED had hyponatremia. Age, number of medications taken, previous history of hyponatremia, heart failure, cirrhosis, pneumonia, sepsis, prescribed drugs including thiazides, opioids (exclude tramadol), or desmopressin or taking PPI together with thiazides was confirmed to correlate with the risk of hyponatremia.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제26권4호
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• pp.173-180
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• 2023

Purpose: Gastro esophageal reflux disease (GERD) is a burdensome disease affecting many children. A clinical examination is reported to be unreliable to diagnose GERD in children. This study aimed to investigate the relationship between the Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) and endoscopic and histopathological findings in children with symptoms suggesting GERD. Changes in the PGSQ score in children with esophagitis as response to one month therapy were recorded as secondary outcome. Methods: This is a prospective cohort study in the pediatric outpatient clinic in an Indonesian tertiary hospital. Children aged 2-17 years old with clinical symptoms suspected of GERD are included in the study. Blinded endoscopic and histopathological examination was performed in all patients before one month proton pump inhibitors (PPI) therapy. The PGSQ information was collected at inclusion and after one month PPI treatment. Results: Fifty-eight subjects were included. Esophagitis was found in 60.9% of subjects according to endoscopy and 58.6% according to histology. There was no significant relationship between the PGSQ score and endoscopic (p=0.781) nor biopsy (p=0.740) examinations. The PGSQ showed a low diagnostic value compared to endoscopy and biopsy (area under the curve [AUC] 0.477, p=0.477, 95% confidence interval [CI] 0.326-0.629 and AUC 0.474, p=0.740 (95% CI 0.321-0.627 respectively). The PGSQ improved significantly post one month of PPI treatment. Conclusion: The PGSQ cannot be used to diagnose esophagitis in children with clinical symptoms suggesting GERD. However, the PGSQ can be used to monitor the treatment response in children with esophagitis.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.1-5
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• 2018

Eosinophilic gastrointestinal disease (EGID), a chronic allergic condition characterized by dense infiltration of eosinophils in the digestive tract, is classified into two types, eosinophilic esophagitis (EoE), which features dense infiltration of eosinophils in the esophageal epithelial layer, and eosinophilic gastroenteritis (EGE), in which the entire digestive tract including the esophagus may be involved. Patients with EoE only have esophageal symptoms, since the other parts of the digestive tract are not involved. On the other hand, 80% of EGE patients have lesions in the small intestine. The esophageal epithelial layer in healthy individuals has no or negligible infiltration by eosinophils, while the small intestinal mucosal layer, especially the distal small intestinal mucosa, can show dense eosinophil infiltration even in the absence of disease. Therefore, histological changes observed in cases of EGE are not qualitative but rather quantitative, as compared to EoE, which has qualitative histopathological changes, indicating important pathogenetic differences between the types. Comparisons of clinical, laboratory, and morphological characteristics between EoE and EGE have revealed several interesting differences. Both EoE and EGE patients are frequently affected by atopic diseases, such as bronchial asthma and allergic rhinitis, and elevated plasma levels of Th2 type cytokines and chemokines are also similarly seen in both. On the other hand, age at diagnosis differs, as the former is generally found in individuals from 30 to 50 years old, while the latter appears in all age groups. Additionally, 80% of patients with EoE are male as compared to only 50% of those with EGE. Furthermore, approximately 60% of patients with EoE respond favorably to proton pump inhibitor (PPI) administration, whereas EGE patients rarely show a response to PPIs. Nevertheless, both diseases show a similarly favorable response to a six foods elimination diet and glucocorticoid administration. These similarities and differences of EoE and EGE provide important clues for understanding the pathogenesis of these EGID types.

• Journal of Digestive Cancer Research
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• 제4권1호
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• pp.1-9
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• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

• 대한한의학방제학회지
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• 제31권4호
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• pp.389-413
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• 2023

Objectives : This study aimed to review the current trends in experimental studies on the use of natural products for treatment of gastroesophageal reflux disease (GERD). Methods : Experimental studies assessing the efficacy of natural products against GERD were searched on PubMed. Articles were selected based on predefined inclusion and exclusion criteria and then analyzed for experimental methods, interventions, and result analysis techniques. Results : A total 37 studies were included in this review. Predominantly, in vivo experiments were conducted to induce GERD through surgery, involving the ligation of the pylorus and the transitional junction between the corpus and the forestomach using 7-week-old male Sprague-Dawley rats. The acute induction model, sacrificing animals after a single administration following GERD induction, was mainly used.The utilization of cell experiments was relatively infrequent, with a focus on assessing antioxidant and anti-inflammatory effects via the treatment of the RAW 264.7 cell line with lipopolysaccharides treatment. Glycyrrhizae Radix et Rhizoma, Pinelliae Tuber, Ginseng Radix and Zingiberis Rhizoma were used as single ingredients, and herbal formula, STW-5 (iberogast), Rikkunshito (六君子湯), Banhasasim-tang (半夏瀉心湯), and Hewei Jiangni granule (和胃降逆湯) were used. Outcome analysis methods encompassed Macroscopic evaluation, esophageal function assessment, blood biomarker analysis, histological examination, protein analysis, gene expression analysis, and gastric juice analysis. Proton pump inhibitors were predominantly employed as positive controls. Conclusions : This study revealed the current trends in non-clinical research evaluating natural products for GERD. Based on the results of this study, we expect that non-clinical research on clinically effective natural products will be revitalized.

• Journal of Gastric Cancer
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• 제8권3호
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• pp.160-165
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• 2008

목적: 소화성 궤양의 급만성 합병증으로 대표되는 천공, 출혈, 협착의 수술적 치료에서 Helicobacter pylori (H. pylori) 제균요법과 proton pump inhibitor의 도입, 중재적 내시경 치료와 같은 비수술적 치료의 발달로 천공, 출혈 등의 급성기 합병증의 수술은 점차 감소되고 있다. 그러나 내과적 소화성 궤양의 협착, 폐색에 대한 비수술적 치료의 결과는 만족스럽지 못한 상태로 수술의 역할이 중요하다. 이에 저자들은 만성 소화성 궤양으로 위출구 폐색을 동반한 환자들의 수술적 치료 후 임상결과를 분석하고자 하였다. 대상 및 방법: 1994년 1월부터 2007년 12월까지 국립의료원 외과에서 소화성 궤양 폐색으로 수술한 31명의 환자를 후향적으로 분석하였고, 이전의 궤양 수술로 인한 유착성 폐색 및 천공이나 출혈로 인한 응급수술시 발견된 폐색동반의 예는 제외하였다. 각 임상병리학적 결과를 수술방법에 따라 우회수술군과 절제수술군으로 분류하였고, 수술결과의 평가는 Visick score를 이용하였다. 수술 후 재발의 기준은 소화성 궤양의 임상증상이 나타나 내시경으로 확진된 경우만을 포함하였다. 결과: 우회수술군이 6명(19.4%), 절제수술군이 25명(80.6%)이었다. 평균 연령은 57.5세(25~81세)이었고, 남자 29명(93.5%), 여자 2명(6.5%)이었다. 평균 증상 지속기간 29.6개월이었고, 흡연자가 19명(61.3%), NSAID 복용자가 6명(19.4%), H. pylori 양성환자가 7명(22.6%) 있었다. 수술 전 내시경적 확장술은 2명에서 시도되었으며, 주병변의 위치는 위, 십이지장이 각각 9명, 20명, 양쪽이 2명이었다. 수술 후 합병증은 13명 (41.9%)에서, 궤양의 재발은 2명(6.5%)에서 있었고, 재수술이 4명(12.9%)에서 필요하였다. 평균 Visick score는 1.8 (1~4)이었다. 우회수술군과 절제수술군의 비교에서 두 군의 임상병리학적 차이는 없었으며, 두 군에서 각각 1명이 재발되었고 합병증은 각각 5명(83.3%), 8명(32%)으로 우회수술군에서 많았으나 통계적 유의성은 없었다(P=0.175). 평균 Visick score는 각각 3.0점, 1.6점으로 절제수술군에서 좋은 결과를 보였다(P=0.001). 결론: 만성 소화성 궤양으로 배출구 폐색을 동반한 환자의 치료에 있어서 내시경적 확장술 등의 비수술적 치료가 비교적 좋은 결과를 보고하고 있지만 여전히 수술은 중요한 치료 방법이다. 궤양 폐색의 수술적 치료시 악성 궤양과의 감별이 용이하지 않고 수술 후 환자의 만족도를 고려한다면 우회수술보다는 절제수술이 바람직한 술식으로 생각된다.

• 한국임상약학회지
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• 제21권2호
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• 대한한방내과학회지
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• 제37권1호
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• pp.90-108
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• 2016

Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

• 대한의생명과학회지
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• 제13권3호
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• pp.197-206
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• 2007

P2X receptors are membrane-bound ion channels that conduct $Na^+,\;K^+$, and $Ca^{2+}$ in response to ATP and its analogs. There are seven subunits identified so far ($P2X_1-P2X_7$). $P2X_2$ receptors are known to be expressed in a wide range of organs including brains and adrenal grands. PC12 cells are originated from adrenal grand and differentiated by nerve growth factor or pituitary adenylate cyclase activating poly peptide (PACAP). Previous studies indicate that $P2X_2$ receptor activation in PC12 cells couples to $Ca^{2+}-dependent$ release of catecholamine and ATP. It is known that acidic pH potentiates ATP currents at $P2X_2$ receptors. This leads to a hypothesis that $P2X_2$ receptors may play an important role in PC12 cell differentiation, one of the characteristics of which is neurite outgrowth, induced by the hormones under lower pH. In the present study, we isolated several clones which potentiate neurite outgrowth by PACAP in acidic pH (6.8), but not in alkaline pH (7.6). RT-PCR and electrophysiology data indicate that these clones express only functional $P2X_2$ receptors in the absence or presence of PACAP for 3 days. Potentiation of neurite outgrowth resulted from PACAP (100 nM) in acidic pH is inhibited by the two P2X receptor antagonists, suramin and PPADS ($100\;{\mu}M)$ each), and exogenous exprerssion of ATP-binding mutant $P2X_2$ receptor subunit ($P2X_2[K69A]$). However, acid sensing ion channels (ASICs) are not involved in PACAP-induced neurite outgrowth potentiation in lower pH since treatments of an inhibitor of ASICs, amyloride ($10\;{\mu}M$), did not give any effects to neurite extension. The vesicular proton pump ($H^+-ATPase$) inhibitor, bafilomycin (100 nM), reduced neurite extension indicating that ATP release resulted from $P2X_2$ receptor activation in PC12 cells is needed for neurite outgrowth. These were confirmed by activation of mitogen activated protein kinases, such as ERKs and p38. These results suggest roles of ATP and $P2X_2$ receptors in hormone-induced cell differentiation or neuronal synaptogenesis in local acidic environments.

• 대한후두음성언어의학회지
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• 제23권1호
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• pp.43-47
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• 2012

Background and Objectives : Laryngopharyngeal reflux disease (LPRD) originates from regurgitation of gastric contents to the laryngopharynx, and it is relatively common disease in otolaryngology. Proton-pump inhibitor (PPI) medication is frequently using treatment method in present time, but controversies exist regarding treatment for it. High-resolution manometry (HRM) system is a newly developed device that using 36 channels and pressure topography plotting program, checking the function and status of esophagus. The aim of this study was to evaluate clinical usefulness of HRM in LPRD patients who do not response to PPI medication. Materials and Method : From July 2009 to July 2010, a total of 99 patients who were suspected LPRD according to symptoms (Reflux Symptom Index >13) and laryngoscopic findings (Reflux Finding Score >7) were retrospectively enrolled in this study. Patients were consisted of 31 men and 68 women, the mean age was 51.8 years, the mean BMI was 22.46. Patients have taken PPI medication for 2 months, after medication, they performed HRM. Comparative analysis was performed with results of the difference in symptoms. Results : In 99 patients, 37 patients (37.4%) show not improvement of LPRD symptoms after PPI medication. Among them, 18 patients (48.6%) showed abnormal findings that were classified as Peristaltic dysfunction (38.9%), Diffuse esophageal spasm (11.1%), Relaxation impairment of LES (11.1%), Achalasia (5.6%), Hypotensive LES (11.1%), Relaxation impairment of UES (11.1%), Nutcracker esophagus (5.6%), Decreased resting pressure (5.6%). Other 62 patients (62.6%) show improvement of LPRD symptoms, 23 patients (37.1%) showed abnormal findings. Most common finding was Peristaltic dysfunction (43.4%) More prevalent abnormal findings of HRM were found in patients who revealed no response to PPI medication (48.6% vs. 37.1%), but it does not reach the statistical significance. Conclusion : Although statistical significances is not showed, the difference observed in the frequency of HRM abnormal finding between response and no response for PPI medication. It has been estimated that HRM may be used to determine differential diagnosis in patients with LPRD. Further studies in lager population containing normal controls will be needed to prove clinical usefulness.