Pediatric patients with coronavirus disease 2019 (COVID-19) are increasing, and severe cases such as multisystem inflammatory syndrome are being reported. Nafamostat, a repurposing drug, is currently being explored for the treatment of COVID-19 in adults. However, the data supporting its exposure in pediatrics remains scarce. Physiologically-based pharmacokinetic (PBPK) modeling enables the prediction of drug exposure in pediatrics based on ontogeny of metabolic enzymes and age dependent anatomical and physiological changes. The study aimed to establish a PBPK model of nafamostat in adults, then scale the adult PBPK model to children for predicting pediatric exposures of nafamostat and an optimal weight-based nafamostat dose in pediatric population. The developed model adequately described adult exposure data in healthy volunteers following i.v. administration with three doses (10, 20, and 40 mg). Scaling adult PBPK models to five pediatric groups predicted that as age advances from neonate to adult, the exposure of nafamostat slightly increased from neonate to infant, steadily decreased from infant to child, and then increased from child to adult after the administration of 0.2 mg/kg/h for 14 days, a dosing regimen being conducted in a clinical trial for COVID-19. Based on the fold change of predicted area under the curve for the respective pediatric group over those of adults, weight-based dosages for each pediatric group may be suggested. The novel PBPK model described in this study may be useful to investigate nafamostat pharmacokinetics in a pediatric subgroup further.

BACKGROUND AND OBJECTIVES: he patients with atrial septal defect generally have no symptoms in the childhood, and have nonspecific symptoms such as dyspnea on exertion, fatigue, and palpitation even in the late period of adult. Thus delayed diagnosis for whom surgical correction was undoubtedly needed remains to be resolved. Accordingly, the simple and noninvasive method such as electrocardiography in patients with atrial septal defect having the nonspecific symptoms or having no symptoms warrants to be developed. This study was performed to see whether the crochetage pattern on R wave in inferior limb leads is effective for the electrocardiographic diagnosis of atrial septal defect and relates to the magnitude of left to right shunt. METHODS: Our subjects were 129 patients diagnosed as the atrial septal defect by the echocardiography and cardiac catheterization from January 1992 to June 1998. We selected 57 persons, as control group, who showed the normal findings under the echocardiography and also showed the incomplete right bundle branch block on the electrocardiography. We compared the frequency of the crochetage pattern in inferior limb leads between the two groups. Also we compared the frequency of the crochetage pattern before operation and after operation according to the quantity of the left to right shunt in the operated 40 patients with atrial septal defect. RESULTS: ) The crochetage pattern was observed in 61.2% in patients with atrial septal defect and its frequency was greater than that of the control group (38.6%, p=0.005). 2) The crochetage pattern was disappeared by the operation in 16/29 patients (55.2%, p=0.001). 3) The frequency of disappearance of the crochetage pattern after operation differed significantly according to shunt severity: 72.2% for a Qp/Qs> or =3.0 group, 18.2% for a Qp/Qs<3.0 group (p=0.015). CONCLUSION: The crochetage pattern on R wave in inferior limb leads was helpful to the electrocardiographic diagnosis of the atrial septal defect. The disappearance of the crochetage pattern after operation was correlated with shunt severity.
Adult ; Bundle-Branch Block ; Cardiac Catheterization ; Cardiac Catheters ; Delayed Diagnosis ; Diagnosis ; Dyspnea ; Echocardiography ; Electrocardiography* ; Extremities* ; Fatigue ; Heart Septal Defects, Atrial* ; Humans

Cell motility is essential for a wide range of cellular activities including anigogenesis as well as metastasis of tumor cells. Ras has been implicated in cell migration and invasion, and functions at upstream of mitogen-activated protein kinase (MAPK) families, which include extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK. In the present study, we examined the role of JNK in endothelial cell motility using stable transfectant (DAR-ECV) of ECV304 endothelial cells expressing previously established oncogenic H-Ras (leu 61). DAR-ECV cells showed an enhanced angiogenic potential and motility (approximately 2-fold) compared to ECV304 cells. Western blot analysis revealed constitutive activation of JNK in DAR-ECV cells. Pretreatment of JNK specific inhibitors, curcumin and all trans-retinoic acid, decreased the basal motility of DAR-ECV cells in a dose-dependent manner. These inhibitors also suppressed the motility stimulated by known JNK agonists such as TNFalpha and anisomycin. To further confirm the role of JNK, ECV304 cells expressing dominant active SEK1 (DAS-ECV) were generated. Basal non-stimulated levels of the cellular migration were greater in DAS-ECV clones than those in control ECV304 cells. These results suggest that Ras-SEK1-JNK pathway regulates motility of endothelial cells during angiogenesis.
Anisomycin/pharmacology ; Cell Line ; *Cell Movement ; Curcumin/pharmacology ; Endothelium, Vascular/cytology/*physiology ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Extracellular Matrix/metabolism ; Genes, ras/genetics ; Human ; Matrix Metalloproteinases/physiology ; Mitogen-Activated Protein Kinases/*metabolism ; Neovascularization, Physiologic ; Support, Non-U.S. Gov't ; Tretinoin/pharmacology ; Tumor Necrosis Factor/pharmacology ; Umbilical Veins/cytology ; Urinary Plasminogen Activator/physiology

Cell motility is essential for a wide range of cellular activities including anigogenesis as well as metastasis of tumor cells. Ras has been implicated in cell migration and invasion, and functions at upstream of mitogen-activated protein kinase (MAPK) families, which include extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK. In the present study, we examined the role of JNK in endothelial cell motility using stable transfectant (DAR-ECV) of ECV304 endothelial cells expressing previously established oncogenic H-Ras (leu 61). DAR-ECV cells showed an enhanced angiogenic potential and motility (approximately 2-fold) compared to ECV304 cells. Western blot analysis revealed constitutive activation of JNK in DAR-ECV cells. Pretreatment of JNK specific inhibitors, curcumin and all trans-retinoic acid, decreased the basal motility of DAR-ECV cells in a dose-dependent manner. These inhibitors also suppressed the motility stimulated by known JNK agonists such as TNFalpha and anisomycin. To further confirm the role of JNK, ECV304 cells expressing dominant active SEK1 (DAS-ECV) were generated. Basal non-stimulated levels of the cellular migration were greater in DAS-ECV clones than those in control ECV304 cells. These results suggest that Ras-SEK1-JNK pathway regulates motility of endothelial cells during angiogenesis.
Anisomycin/pharmacology ; Cell Line ; *Cell Movement ; Curcumin/pharmacology ; Endothelium, Vascular/cytology/*physiology ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Extracellular Matrix/metabolism ; Genes, ras/genetics ; Human ; Matrix Metalloproteinases/physiology ; Mitogen-Activated Protein Kinases/*metabolism ; Neovascularization, Physiologic ; Support, Non-U.S. Gov't ; Tretinoin/pharmacology ; Tumor Necrosis Factor/pharmacology ; Umbilical Veins/cytology ; Urinary Plasminogen Activator/physiology

We report here on a case of peripheral T-cell lymphoma of the ovary as the initial manifestation of extranodal disease. A 45-year-old woman presented with an incidentally detected, ovarian mass. Contrast-enhanced CT scans showed a 6x5.3 cm diameter, heterogeneously enhancing mass in the right adnexa that invaded the adjacent uterus. An exploratory laparotomy revealed a solid mass in the right adnexa, which invaded the uterine cornus. Histological diagnosis was made as a peripheral T-cell lymphoma of the ovary.
Cornus ; Diagnosis ; Female ; Humans ; Laparotomy ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral* ; Middle Aged ; Ovary ; Tomography, X-Ray Computed ; Uterus

PURPOSE: To compare virtual gastroscopy using spiral CT with conventional endoscopy for the detection andevaluation of gastric lesions. MATERIALS AND METHODS: During a previous six-month period, 30 patients withpathologically-proven gastric lesions underwent conventional endoscopy and virtual gastroscopy using spiral CT.There were 18 cases of advanced gastric carcinoma, eight benign ulcers, and four submucosal tumors(two leiomyomas,two lymphomas). Source images of virtual gastroscopy were three-dimensionally reconstructed within an AdvantageWindows Workstation and virtual gastroscopy images were obtained using Navigator Software. On analysis, imageswere graded according to their quality (excellent, good, poor). Virtual gastroscopy images were interpreted by tworadiologists blinded to conventional endoscopic findings, and were subsequently compared with endoscopic findingsin terms of detectability and findings. In the cases of advanced gastric carcinoma, lesions were classifiedaccording to Borrmann's system. RESULTS: For virtual gastroscopy, overall image quality was excellent in 21cases(70%), good in five(17%), and poor in four(13%). Lesions were detected in 25 cases(83%). Among the 18advanced gastric carcinomas, virtual gastroscopy image quality was excellent in 14 cases(78%), good in two(11%),and poor in two(11%). Lesions were detected in 16 cases(89%). Two Borrmann type IV cases were not detected. Amongthe eight benign ulcers, virtual gastroscopy image quality was excellent in three cases(38%), good in three(38%),and poor in two(25%). The detection of lesion was possible in five cases(63%). In all submucosal tumors, virtualgastroscopy image quality was excellent. Lesions were detected in all cases. CONCLUSION: Virtual gastroscopyusing spiral CT is safe and noninvasive, and for the evaluation of gastric lesions may be complementary to axialCT. It successfully detects gastric lesions, and in depicting the pattern of gastric folds its image quality isexcellent.
Endoscopy ; Gastroscopy* ; Humans ; Tomography, Spiral Computed* ; Ulcer

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of computerized dynamic posturography (CDP) in patients with acute vestibular neuritis (AVN) by identifying the recovery period of Sensory Organization Test (SOT) and comparing the result of SOT with those of the vestibulo-ocular reflex (VOR) tests and subjective symptoms. SUBJECTS AND METHOD: A prospective study was conducted on 41 patients who were diagnosed with AVN. The SOT was measured daily until the equilibrium composite score recovered the normal value. A survey, composing of questionnaires on Visual Analogue Scale (VAS), Dizziness Handicap Inventory (DHI), motion sensitive quotient (MSQ) and Activities-Specific Balance Confidence Scale (ABC), was conducted on the patient's initial visit and on the day the normal value of SOT was recovered. Videonystagmography and the caloric test were also performed, and the results were compared with those of the SOT. RESULTS: The mean duration from the onset of vertigo to the recovery of SOT scores was 3.7±2.9 days (median 3.0 days) and that from the onset of vertigo to the disappearance of spontaneous nystagmus was 17.1±27.2 days (median 6.0 days). The scores of 4 questionnaires (VAS, DHI, MSQ, and ABC) were significantly different between the initial day and the day of recovery to the normal value of SOT (p<0.001). However, the velocity of spontaneous nystagmus on the initial visit and the degree of canal paresis from the caloric test showed no significant correlations to recovery duration from the onset of vertigo to the normalization of SOT score. CONCLUSION: The recovery duration of vestibulospinal reflex (VSR) is much shorter than that of VOR in patients with AVN. The recovery of subjective symptoms showed close correlation with the recovery of VSR, but the results of VSR was not correlated with that of VOR. Therefore, CDP could be a very useful test for monitoring the resolution of subjective symptoms in patients with AVN.
Caloric Tests ; Compensation and Redress* ; Cytidine Diphosphate ; Dizziness ; Humans ; Methods ; Paresis ; Prospective Studies ; Reference Values ; Reflex ; Reflex, Vestibulo-Ocular ; Vertigo ; Vestibular Neuronitis*

It is challenging to achieve sufficient hearing gain in patients with mixed hearing loss. In chronic middle ear diseases, conventional passive reconstructive surgeries often result in suboptimal hearing gain and additional hearing aids may have limitations due to insufficient sound amplification, occlusion effect, acoustic feedback, and skin irritation. Middle ear implantation (MEI) using Vibrant Soundbridge (VSB) is another option for auditory rehabilitation in mixed hearing loss as well as sensorineural hearing loss. The floating mass transducer of VSB can be placed on various middle ear structures either directly or using different types of couplers in order to deliver vibratory mechanical energy to the cochlea. We report a patient who presented with bilateral mixed hearing loss due to chronic otitis media and had limitations using conventional hearing aids in the worse hearing ear. The patient was successfully treated with MEI using the Bell coupler together with middle ear surgery in a single step.
Acoustics ; Cochlea ; Ear ; Ear, Middle* ; Hearing ; Hearing Aids ; Hearing Loss, Mixed Conductive-Sensorineural* ; Hearing Loss, Sensorineural ; Humans ; Ossicular Prosthesis* ; Otitis Media ; Rehabilitation ; Skin ; Transducers

OBJECTIVE: The purpose of this study was to identify the diverse patterns of nystagmus and analyze their clinical significance in benign paroxysmal positional vertigo (BPPV) of the anterior semicircular canal. METHODS: Fifty-three patients diagnosed with anterior canal BPPV (AC-BPPV) were analyzed retrospectively. Patients were classified according to the presence or absence of the torsional component of the nystagmus and the direction of Dix-Hallpike test which induced the nystagmus. We compared the clinical characteristics and treatment outcomes among the different patient groups. RESULTS: There were 11 patients with unilateral down beat (DB) nystagmus, 11 patients with bilateral DB nystagmus, 14 patients with ipsilateral torsional down beat (TDB) nystagmus, 7 patients with contralateral TDB nystagmus, and 7 patients with bilateral TDB nystagmus. There were no differences between the unilateral and the bilateral DB groups in terms of the duration of nystagmus or vertigo and the number of treatment sessions. In addition, the ipsilateral TDB group showed no significant clinical difference compared to the contralateral or bilateral TDB group. CONCLUSION: Various nystagmus patterns can be seen in AC-BPPV. There was no statistically significant difference in the clinical characteristics according to the different nystagmus patterns. This information may be helpful for clinicians in counseling and managing the patients with AC-BPPV.
Benign Paroxysmal Positional Vertigo ; Counseling ; Humans ; Retrospective Studies ; Semicircular Canals ; Vertigo

OBJECTIVE: The purpose of this study was to identify the influence of sleep position on benign paroxysmal positional vertigo (BPPV). METHODS: Four hundred sixty patients diagnosed as posterior or horizontal canal BPPV were analyzed retrospectively. All patients were asked about their preferred sleep positions among the following four choices: supine, right or left lateral, or no predominant side via questionnaire at initial visit and after 1month. Patients were classified into two groups: affected side group meaning that the patient preferred to sleep ipsilateral to the affected ear and other position group including all positions other than lying lateral to the affected side after treatment. We analyzed the change in the sleep pattern after treatment and compared the recurrence rate between the two groups. RESULTS: Our study included 244 patients with posterior canal BPPV (PC-BPPV) and 216 patients with horizontal canal BPPV (HC-BPPV). Statistically significant correlation was demonstrated between sleep position side and the affected side by BPPV. The number of patients who slept on the affected side by BPPV decreased, while the number of patients who slept on the healthy side increased significantly after treatment. There was no statistically significant difference in the recurrence rate between the two groups. CONCLUSION: There was significant correlation between the sleep position side and the affected side in PC-BPPV and HC-BPPV. The patient had a tendency to avoid lying lateral to the affected side by BPPV during sleep after treatment, however the change in sleep position did not influence the recurrence rate of BPPV.
Benign Paroxysmal Positional Vertigo ; Deception ; Ear ; Humans ; Recurrence ; Retrospective Studies