A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is developed and validated for quantification of venlafaxine in human plasma with simple liquid-liquid extraction step consisted of extraction with ether and dichloromethane for 10 min and mixing with 1 M sodium acetate in human plasma using fluoxetine as an internal standard (IS). The analyte are separated using an isocratic mobile phase consisted of acetonitrile and 5 mM ammonium formate (4/3, v/v) on a isocratic YMC hydrosphere C18 (2.0x50.0 mm, 3.0 microm) column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective [M+H](+) ions, m/z 278.2-->260.3 and m/z 310.1-->148.1 for quantification of venlafaxine and IS, respectively. The standard calibration curves showed good linearity within the range of 1.0-200.0 ng/mL (r2=0.9986, 1/chi2 weighting). The lower limit of quantification (LLOQ) was 1.0 ng/mL. The retention times of venlafaxine and IS were 0.6 min and 0.7 min that means the potential for the high-throughput potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied to bioequivalence study after 75-mg of venlafaxine sustained-release (SR) capsule in 24 healthy Korean subjects.
Ammonium Compounds ; Calibration ; Chromatography, Liquid ; Ether ; Fluoxetine ; Humans ; Ions ; Liquid-Liquid Extraction ; Methylene Chloride ; Pharmacokinetics ; Plasma* ; Sodium Acetate ; Tandem Mass Spectrometry ; Therapeutic Equivalency* ; Venlafaxine Hydrochloride

Glucocorticoids are usually given according to a standard dosing protocol regardless of individual difference. We evaluated the pharmacokinetic characteristics of methylprednisolone and the degree of interpatient variation in stable Korean renal transplant recipients during the period of 15-21 days after transplantation. This study included 23 renal transplant recipients, 13 males and 10 females, who received kidneys from living donors with stable graft function and without episode of acute rejection. On the study day at 8 A.M., 16.3mg of ethylprednisolone sodium succinate (i.v.) was administered to each patient instead of usual dose (20mg) of prednisolone (p.o.) after sampling of 7cc of baseline blood and additional blood samples were drawn after starting infusion. Plasma was separated and analyzed for methylprednisolone level using high performance liquid chromatography (HPLC) assay, and parameters for pharmacokinetics were calculated. There was significant interpatient variation in the pharmacokinetics of methylprednisolone in our patients group. There was no significant difference in the pharmacokinetic parameters between patients with and without side effects of steroid. Korean renal transplant recipients had higher volume of distribution than black renal transplant recipients; lower clearance than white renal transplant recipients; longer t1/2 than both black and white renal transplant recipients. Even if the number of patients included in this study was too small to reach conclusion, the differences in the pharmacokinetics of glucocorticoids do not seem to be a significant risk factor for side effects of steroid after transplantation. It may be necessary to individualize the dose of a glucocorticoid to achieve an optimal effect and also we need to establish a new steroid regimen protocol for Korean renal transplant recipients.
Chromatography, Liquid ; Female ; Glucocorticoids ; Humans ; Individuality ; Kidney ; Kidney Transplantation ; Living Donors ; Male ; Methylprednisolone* ; Pharmacokinetics ; Plasma ; Prednisolone ; Risk Factors ; Sodium ; Succinic Acid ; Transplantation* ; Transplants

By means of retrospective quantitative neuroanatomic imaging, the authors assessed the corpus callosum and the lateral venticle in the boys with attention deficit hyperactivity disorder (ADHD). The midsagittal cross-sectional area of the corpus callosum, divided into seven regions, and the axial ventricle-brain ratio were measured from magnetic resonance images of 18 boys with ADHD and 15 comparison boys. Two anterior regions, the menu and the rostral body, were found to have significantly smaller areas in the ADHD boys. There was no significantly difference in ventricle-brain ratio between ADHD and comparison boys. This finding supports the theory of abnormal frontal lobe development in ADHD.
Attention Deficit Disorder with Hyperactivity* ; Corpus Callosum* ; Frontal Lobe ; Humans ; Lateral Ventricles* ; Magnetic Resonance Imaging* ; Male ; Retrospective Studies

Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. It is unnecessary to employ TDM for the majority of medications, and it is used mainly for monitoring drugs with narrow therapeutic ranges, drugs with marked pharmacokinetic variability, medications for which target concentrations are difficult to monitor, and drugs known to cause therapeutic and adverse effects. The process of TDM is predicated on the assumption that there is a definable relationship between dose and plasma or blood drug concentration, and between concentration and therapeutic effects. TDM begins when the drug is first prescribed, and involves determining an initial dosage regimen appropriate for the clinical condition and such patient characteristics as age, weight, organ function, and concomitant drug therapy. When interpreting concentration measurements, factors that need to be considered include the sampling time in relation to drug dose, dosage history, patient response, and the desired medicinal targets. The goal of TDM is to use appropriate concentrations of difficult-to-manage medications to optimize clinical outcomes in patients in various clinical situations.
Algorithms ; Dose-Response Relationship, Drug ; Drug Monitoring/*methods/trends ; Forecasting ; Humans ; Patient Compliance ; Pharmacokinetics

When operations in the field of plastic surgery are performed under local anesthesia, the degree of pain suffering the patients becomes different depending on the kind, dosage effective duration of anesthetic agent and the technique of the operator. Patients suffer from pain physically and psychologically when skin infiltration is carried out. Recently, out-patient surgery has increased in number, so the necessity of more complete analgesia for the patient undergoing surgery is required. Patients were operated under the local infiltrative anesthesia, and the supplemental intravenous anesthesia to kill pain. Patients were randomly divided into four groups differing in combinations of intravenous anesthetic agents, such as ketamine, midazolam, fentanyl that have potent analgesic sedative and amnesic effects. By random allocation patients received ketamine and midazolam(Group I), ketamine and fentanyl(Group II), midazolam and fentany l (Group III), ketamine, fentanyl arts midazolam(Group IV). The purpose of this study is to focus on the results obtained in four groups for finding out a more safe and less complicated combination of intravenous anesthetic agents and for standardization of dosage. In conclusion the group I (ketamine and midazolam) showed better results than other groups for the following reasons; no significant change in vital signs, no hypoxia no complication such as nausea, headache unpleasant dream, and hallucination, potent analgesia effects, amnesia. We have found this combination to be a highly satisfactory anesthesia and analgesia technique for outpatient plastic surgery from the standpoints of the surgeon and the patient.
Amnesia ; Analgesia ; Anesthesia ; Anesthesia and Analgesia ; Anesthesia, Intravenous* ; Anesthesia, Local* ; Anesthetics ; Anesthetics, Intravenous ; Anoxia ; Dreams ; Fentanyl ; Hallucinations ; Headache ; Humans ; Ketamine ; Midazolam ; Nausea ; Outpatients ; Random Allocation ; Skin ; Surgery, Plastic* ; Vital Signs

When operations in the field of plastic surgery are performed under local anesthesia, the degree of pain suffering the patients becomes different depending on the kind, dosage effective duration of anesthetic agent and the technique of the operator. Patients suffer from pain physically and psychologically when skin infiltration is carried out. Recently, out-patient surgery has increased in number, so the necessity of more complete analgesia for the patient undergoing surgery is required. Patients were operated under the local infiltrative anesthesia, and the supplemental intravenous anesthesia to kill pain. Patients were randomly divided into four groups differing in combinations of intravenous anesthetic agents, such as ketamine, midazolam, fentanyl that have potent analgesic sedative and amnesic effects. By random allocation patients received ketamine and midazolam(Group I), ketamine and fentanyl(Group II), midazolam and fentany l (Group III), ketamine, fentanyl arts midazolam(Group IV). The purpose of this study is to focus on the results obtained in four groups for finding out a more safe and less complicated combination of intravenous anesthetic agents and for standardization of dosage. In conclusion the group I (ketamine and midazolam) showed better results than other groups for the following reasons; no significant change in vital signs, no hypoxia no complication such as nausea, headache unpleasant dream, and hallucination, potent analgesia effects, amnesia. We have found this combination to be a highly satisfactory anesthesia and analgesia technique for outpatient plastic surgery from the standpoints of the surgeon and the patient.
Amnesia ; Analgesia ; Anesthesia ; Anesthesia and Analgesia ; Anesthesia, Intravenous* ; Anesthesia, Local* ; Anesthetics ; Anesthetics, Intravenous ; Anoxia ; Dreams ; Fentanyl ; Hallucinations ; Headache ; Humans ; Ketamine ; Midazolam ; Nausea ; Outpatients ; Random Allocation ; Skin ; Surgery, Plastic* ; Vital Signs

No abstract available.
Hepatitis*

We studied retrospectively on clinical assessment of treatment in myasthenic patients who visited on our department regularly since 1985. They were divided as a group based on therapeutic modalities such as a thymectomy, steroid therapy. Combined therapy(steroid and thymectomy), plasma exchange. And whole body irradiation. We evluated clinical effectiveness of these therapeutic modalities and come up with following conclusions. Alltherapeutic modalities showed effectiveness. In steroid therapy, thymectomy and the combined therapy. W needed at least 6-24 months for clinical improvement. In thymectomy, rognosis was depend on the number of germinal centers. In whole body irradiation. Effectiveness was shown at 5h week and continued to 6th to 12th months. We also noted that symptomatic improvement was correlated with decreased lymphocyte counts. The effect of plasma exchange was rapid but only short duration.
Germinal Center ; Humans ; Lymphocyte Count ; Myasthenia Gravis* ; Plasma Exchange ; Retrospective Studies ; Thymectomy ; Whole-Body Irradiation

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.
Body Fluids ; Cardiovascular Diseases ; Diagnosis ; Drug Delivery Systems ; Exocytosis ; Exosomes* ; MicroRNAs ; Molecular Imaging ; Neurodegenerative Diseases ; Nucleic Acids ; Pathologic Processes ; Stem Cells ; Therapeutic Uses

Background: Early-onset dementia (EOD) is still insufficiently considered for healthcare policies. We investigated the effect of socio-environmental factors on the long-term survival of patients with EOD. Methods: This retrospective cohort study utilized the Korean National Health Insurance Database from 2007 to 2018. We enrolled 3,825 patients aged 40 to 65 years old with all types of dementia newly diagnosed in 2009 as EOD cases. We defined socioeconomic status using the national health insurance premium (NHIP) levels. Residential areas were classified into capital, metropolitan, city, and county levels. All-cause mortality was the primary outcome. Kaplan-Meier curves and log-rank tests were employed. Further, Cox-proportional hazards models were established. Results: The mean survival of the fourth NHIP level group was 96.31 ± 1.20 months, whereas that of the medical-aid group was 85.53 ± 1.30 months (P < 0.001). The patients living in the capital had a mean survival of 95.73 ± 1.34 months, whereas those living in the county had 89.66 ± 1.75 months (P = 0.035). In the Cox-proportional hazards model, the medical-aid (adjusted hazard ratio [aHR], 1.67; P < 0.001), first NHIP level (aHR, 1.26; P = 0.012), and second NHIP level (aHR, 1.26; P = 0.008) groups were significantly associated with a higher long-term mortality risk. The capital residents exhibited a significantly lower long-term mortality risk than did the county residents (aHR, 0.82; P = 0.041). Conclusion Socioeconomic status and residential area are associated with long-term survival in patients with EOD. This study provides a rational basis for establishing a healthcare policy for patients with EOD.