Outcomes of vaginal hysterectomy combined with anterior and posterior colporrhaphy for pelvic organ prolapse: a single center retrospective study

Objective@#To evaluate the efficacy of vaginal hysterectomy combined with anterior and posterior colporrhaphy (VH APR) for the management of pelvic organ prolapse (POP). @*Methods@#A total of 610 patients with POP who underwent VH APR from January 2010 to June 2019 at Asan Medical Center were included in this study. We analyzed the patient characteristics and surgical outcomes. In addition, we compared the POP quantification system (POP-Q) pre- and postoperatively at 2 weeks, 3 months, and 1 year, and analyzed the risk factors for recurrence. @*Results@#The mean age of the patients was 65.5±7.6 years. The most common preoperative POP-Q stage was stage 2 (60.8%), followed by stage 3 (35.9%). Complications were identified during surgery in 1.6% of the patients. The most common postoperative complication (6.4%) was voiding difficulty. All POP-Q scores significantly decreased at 1 year after surgery (P<0.0001). The recurrence rate was 9.6%, and most recurrences (77.5%) occurred in the anterior compartment. An advanced stage of preoperative POP was a risk factor for recurrence (stage 3 or 4 vs. stage 1 or 2; odds ratio [OR], 5.337, 95% confidence interval [CI], 2.58-11.036, P<0.0001). Only two patients underwent surgical correction for POP recurrence, and most of the remaining patients did not undergo further treatment for prolapse. @*Conclusion@#VH APR is a safe and effective surgical procedure for POP, with a low recurrence rate. In addition, advanced preoperative stage was the only risk factor for recurrent POP.

Mitogen Activated Protein Kinase Family Proteins and c-jun Signaling in Injury-induced Schwann Cell Plasticity

Schwann cells (SCs) in the peripheral nerves myelinate axons during postnatal development to allow saltatory conduction of nerve impulses. Well-organized structures of myelin sheathes are maintained throughout life unless nerves are insulted. After peripheral nerve injury, unidentified signals from injured nerves drive SC dedifferentiation into an immature state. Dedifferentiated SCs participate in axonal regeneration by producing neurotrophic factors and removing degenerating nerve debris. In this review, we focus on the role of mitogen activated protein kinase family proteins (MAP kinases) in SC dedifferentiation. In addition, we will highlight neuregulin 1 and the transcription factor c-jun as upstream and downstream signals for MAP kinases in SC responses to nerve injury.

Expression Profile of Fas-Fas Ligand in Spiral Ganglion Cells During Apoptosis

OBJECTIVES: To examine the expression profile of Fas-Fas ligand (FasL) during glutamate (Glu)-induced spiral ganglion cell (SGC) apoptosis. METHODS: Cultured SGCs were treated with 10-mM, 25-mM, and 50-mM concentrations of Glu and incubated for 24 or 48 hours. The expression intensity of FasL, Fas, caspase 3, and morphology of single SGC were evaluated using immunofluorescence staining. RESULTS: In semiquantitative analysis of the Glu-treated SGC, FasL, and caspase 3 expression intensity were increased with concentration- and time-dependent manner. Fas expression intensity did not change with different concentration at 48 hours. In morphologic analysis of the Glu-treated SGC, number of apoptotic cells were increased with concentration- and time-dependent manner. CONCLUSION: FasL was expressed in apoptotic SGCs, suggesting that the Fas-FasL signaling pathway may be involved in the Glu-induced apoptosis of dissociated SGCs.

Janus Kinase 2 Inhibitor AG490 Inhibits the STAT3 Signaling Pathway by Suppressing Protein Translation of gp130

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STAT3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2alpha. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

Excessive Daytime Sleepiness

Excessive daytime sleepiness (EDS) is a prevalent complaint among patients in psychiatric and medical care. Patients with EDS have often been misdiagnosed with depression due to their complaints of lack of energy and poor concentration. Also, they have even been diagnosed erroneously with a psychotic disorder in case of coexistence with hypnagogic hallucination. EDS can seriously affect the person's quality of life by causing decreased academic achievement or work performance, low self esteem, and social withdrawal. EDS is also frequently associated with various medical and psychiatric conditions, and often fatal traffic or on-the-job accidents. The causes of EDS range from insufficient sleep to central nervous system-originated hypersomnia. The conditions that can lead to EDS include circadian rhythm disorders, primary disorders of alertness such as narcolepsy, sleep-related breathing disorders such as obstructive sleep apnea syndrome, sleep-related movement disorders such as periodic limb movement disorder and restless legs syndrome, chronic medical conditions such as cancer, and medications causing sleepiness. Treatment options should be tailored according to the underlying condition and include sufficient sleep time, light therapy, sleep scheduling, wakefulness-promoting medications, or mechanical airway managements such as nasal continuous positive airway pressure (CPAP).

A Case of a Patient with Both Chorea and Restless Legs Syndrome

The patient was a 44-yr-old man with end-stage renal disease who had developed chorea as a result of hypoglycemic injury to the basal ganglia and thalamus and who was subsequently diagnosed with depression and restless legs syndrome (RLS). For proper management, the presence of a complex medical condition including two contrasting diseases, chorea and RLS, had to be considered. Tramadol improved the pain and dysesthetic restlessness in his feet and legs, and this was gradually followed by improvements in his depressed mood, insomnia, lethargy, and feelings of hopelessness. This case suggests that the dopaminergic system participates intricately with the opioid, serotoninergic, and noradrenergic systems in the pathophysiology of RLS and pain and indirectly of depression and insomnia.

Netrin-1 Specifically Enhances Cell Spreading on Fibronectin in Human Glioblastoma Cells

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against alpha v integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin alpha v beta 3. Since the alpha v subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

The Effect of Total Sleep Deprivation on the Physiological and Cognitive Function / 신경정신의학

OBJECTIVES: Purpose of this study was to investigate physiological and neurocognitive effects of total sleep deprivation by using laboratory blood tests and the computerized neurocognitive function test in healthy subjects. METHODS: Sixteen healthy volunteers participated in this study. Subjects were recommended to remain awake for 48 hours under continuous surveillance. Lab tests of cortisol, prolactin, thyroid hormone, growth hormone, and immunoglobulin (IgG, IgA, IgM, IgD, IgE), CBC, BC and the Vienna test were performed before and after 48 hours of total sleep deprivation. RESULTS: Concentration of T3 and T4 significantly increased after deprivation. In the reaction test, distribution reaction time significantly increased, and correct reaction significantly decreased. In the vigilance test, amount of correct reaction significantly decreased, and the mean value of correct reaction time was significantly delayed. Level of fasting blood sugar, total protein, albumin, alkaline phosphatase and potassium significantly increased, respectively, except for the level of total bilirubin which was decreased. After total sleep deprivation, WBC counts significantly increased. Regarding immunoglobulin level, IgG, IgA and Ag M concentrations appeared to decrease, but the results were not statistically significant. CONCLUSION: The effect of total sleep deprivation on physiological function was significant in the level of thyroid hormone. Although statistically not significant, the results of growth hormone and the immune system showed a trend in relations to the effect of total sleep deprivation. Results of blood chemistry suggest that sleep deprivation may influence metabolism of hepatobiliary system. Cognitive impairment was also seen in reactive and vigilant functions after total sleep deprivation.

Comparison of Narcolepsy with Cataplexy and without Cataplexy: Clinical Variables, HLA-DQB1*0602, and Hypocretin / 신경정신의학

OBJECTIVES: Narcolepsy is a sleep disorder, characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination. Among these symptoms, cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the clinical features, frequency of DQB1*0602 and CSF hypocretin levels in Korean narcoleptics with cataplexy to compare with those who have not cataplexy. METHODS: From August 2003 to July 2005, we selected 72 patients who have narcolepsy confirmed by nocturnal polysomnography and multiple sleep latency test (MSLT) as well as their history and clinical symptoms at Sleep Disorders Clinic of St. Vincent's Hospital, Catholic University of Korea. Patients were divided into 56 cataplexy-positive group (narcolepsy with cataplexy group) and 12 cataplexy-negative group (narcolepsy without cataplexy group). HLA typing was done in all patients for the presence of DQB1*0602, and patients received spinal tapping to measure the level of CSF hypocretin. Clinical variables were examined by semi-structured interview for narcolepsy patients. RESULTS: 1) In cataplexy-positive group, compared with cataplexy-negative group, the frequency of HLA-DQB1*0602 was found to be significantly increased (50 subjects, 89.3% vs. 8 subjects, 50.0%)(p=0.000). 2) In 48 out of 56 cataplexy-positive patients (85.7%), hypocretin levels were decreased (< or =110 pg/ml) or were below the detection limit of assay (<40 pg/ml). However, only 6 out of 16 cataplexy-negative patients (37.5%) exhibited decreased hyopcretin level. The difference between two groups were statistically significant (p=0.000). 3) Cataplexy-positive group, compared to cataplexy-negative group, reported more frequent hypnagogic hallucinations (36 subjects, 64.3% vs. 4 subjects, 25.0%)(p=0.005). However, there were no significant differences in frequency or severity of daytime sleepiness, sleep paralysis and demographic data. 4. In nocturnal polysomnography and MSLT findings, there were no significant differences in all sleep parameters between two groups. CONCLUSION: Higher frequency of HLA-DQB1*0602, and lower hypocretin levels in cataplexy-positive groups than catapelxy-negatives suggest that narcoleptics with cataplexy might be a etiologically different disease entity from narcoleptics without cataplexy. Additionally, Current criteria prevail for the diagnosis of narcolepsy need to be reclassified according to the presence of cataplexy or not.

HLA-DQB1 Allele and Hypocretin in Korean Narcoleptics with Cataplexy

Cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the frequency of the HLA-DQB1 allele and cerebrospinal fluid (CSF) hypocretin levels in Korean narcoleptics with cataplexy as compared with those who do not have cataplexy. Seventy-two narcoleptics were selected based on polysomnography and multiple sleep latency test as well as their history and clinical symptoms at Sleep Disorders Clinic. The patients were divided into a narcolepsy with cataplexy group (n=56) and a narcolepsy without cataplexy group (n=16). All patients were subjected to HLA typing to determine the frequency of DQB1 allele and to spinal tapping to measure the level of CSF hypocretin. In cataplexy-positive patients, as compared with cataplexy-negative patients, the frequency of HLA-DQB1*0602 was found to be significantly high (89.3% vs. 50.0%) (p=0.003). On the other hand, the frequency of HLA-DQB1*0601 was found to be significantly low (0% vs. 43.8%) (p<0.001). In 48 of 56 cataplexy-positive patients (85.7 %), hypocretin levels were decreased (< or =110 pg/mL). However, only 6 of 16 cataplexy-negative patients (37.5%) exhibited a decreased hyopcretin level (p<0.001). The high frequency of HLA-DQB1*0602, low frequency of HLA-DQB1*0601 and low hypocretin levels in cataplexy-positive groups suggest that cataplexy-positive narcolepsy might be an etiologically different disease entity from the cataplexy-negative.

Clinical Manifestation, Diagnosis, and Treatment of Obstructive Sleep Apnea Syndrome

No Abstract available.

Gender Differences in Narcolepsy Symptomatology among Adolescents / 수면정신생리

OBJECTIVES: Narcolepsy is characterized by excessive sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination. As there have been few researches on narcolepsy symptomatology in adolescents, we examined gender differences and prevalence of narcolepsy tetrad among students attending high school. METHODS: Total 20, 407 subjects, ages 14-19 years filled out Ullanlinna Narcolepsy Scale (UNS). Subjects whose UNS scores were equal to or more than 14 were interviewed by telephone using semi-structured questionnaire. Variables included questions to evaluate tetrad of narcolepsy. RESULTS: UNS scores were higher in female than male (11.1+/-5.2 vs. 9.6+/-4.5, p or = 14 were significantly higher in female subjects than male ones. However, no significant gender difference was observed in the frequencies of severe sleep attack and cataplexy-like symptoms. Sleep paralysis was most frequently reported during sleep. There was significant correlation between sleep paralysis and hypnagogic hallucination (r=0.235, p< 0.01). CONCLUSIONS: Our findings were that female adolescents complained more frequently narcolepsy symptoms than male subjects. Female adolescents might be more sensitive than male ones to physical complaints such as sleepiness or muscle weakness.

Characteristics of Sleep Apnea Syndrome in the Elderly in a Clinical Setting / 수면정신생리

OBJECTIVES: Much attention has been paid to sleep apnea syndrome (SAS) in the elderly because of its high prevalence. It is expected that SAS in the elderly has both similarities and differences compared to SAS in the young or middle-aged populations. The aim of this study was to elucidate the characteristics and consequences of SAS in the elderly. METHODS: In this study we included 210 young or middle-aged adults between 23 and 59 years (20 women and 190 men) and 65 older adults between 60 and 83 years of age (16 women and 49 men). Respiratory disturbance indices (RDIs) of the study subjects were more than 5 in an overnight polysomnography. They completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Informations about body mass index (BMI), neck, waist, and hip measurements, and blood pressure were obtained. RESULTS: No difference was observed between older adults with SAS (older SAS) and adults aged under 60 with SAS (SAS aged under 60) in RDI, apnea index, % time of oxygen saturation less than 90%, and PSQI. Obstructive apnea index and oxygen desaturation index (ODI) were lower in older SAS. Compared to SAS aged under 60, lowest oxygen saturation and central apnea index were higher in older SAS, but they were statistically not significant. BMI and neck circumference were significantly lower in older SAS compared to SAS aged under 60. Diastolic blood pressure was lower in older SAS compared to SAS aged under 60 with no difference in systolic blood pressure. Older SAS showed lower scores in ESS than SAS aged under 60. Significant correlation was observed between RDI and BMI in SAS aged under 60, but not in the case of older SAS. The relationships between RDI and neck circumference, systolic and diastolic pressure, and ESS were similar. CONCLUSIONS: The elderly with SAS were not over-weight and there was no relationship between body weight and the severity of SAS. Also, the behavioral and cardiovascular effects of SAS were not marked in the elderly, which might be partly explained by decreased ODI and relatively higher lowest oxygen saturation in older SAS. The normal aging process, aside from increased body weight, might contribute to the development of SAS in the elderly with modest complications.

Comparison of Side Effect Profiles between Mirtazapine and Selective Serotonin Reuptake Inhibitors; A Naturalistic Setting / 대한정신약물학회지

OBJECTIVES: Since the efficacy is similar among different antidepressants, side effects, costs, and overdose toxicity are considered preferentially as factors to choose antidepressant. Recently, selective serotonin reuptake inhibitors (SSRIs) are more frequently prescribed than tricyclic antidepressants because of their less frequent side effects. Also the use of noradrenergic and specific serotonergic antidepressants (NaSSA) are increasing. These new antidepressants have characteristic side effect profiles in terms of gastrointestinal side effects, weight gain and sexual dysfunction which serve as direct cause of noncompliance. In the present study, we compared the drug side effects of patients with major depressive disorder who have taken either mirtazapine or SSRIs. METHODS: Among those patients who were treated at Department of Psychiatry, St. Mary's Hospital, The Catholic University of Korea, from Jun, 2002 to July, 2002, we included patients who met DSM-IV criteria for major depressive disorder. Patients who reveive either mirtazapine or SSRIs (fluoxetine, paroxetine) monotherapy as an antidepressant were enrolled. Patients with physical illnesses or poor drug compliance were excluded. A self-rating questionnaire was used to assess the drug side effects. RESULTS: Total 86 patients (mirtazapine;24, SSRIs;62 (fluoxetine 18, paroxetine 44)) were participated in this study. There was no difference at age (mirtazapine;48.0+/-14.0 years, SSRIs;43.3+/-15.6 years), sex ratio (mirtazapine;male 12: female 12, SSRIs;male 24: female 38), and mean duration of administration (mirtazapine;20.2+/-21.5 weeks, SSRIs;32.1+/-50.9 weeks) between two groups. Patients taking mirtazapine have significantly less side effects in terms of decreased appetite, yawn, decreased libido, and anorgasmia. Patients taking SSRIs have significantly less side effects in terms of peripheral edema than mirtazapine. CONCLUSION: Mirtazapine and SSRIs showed differences in some side effects. Mirtazapine showed more favorable side effect profiles in the gastrointestinal and sexual side effects than SSRIs. This data was thought to be useful guidelines in selecting antidepressants hereafter.

Comparison of Side Effect Profiles between Mirtazapine and Selective Serotonin Reuptake Inhibitors; A Naturalistic Setting / 대한정신약물학회지

OBJECTIVES: Since the efficacy is similar among different antidepressants, side effects, costs, and overdose toxicity are considered preferentially as factors to choose antidepressant. Recently, selective serotonin reuptake inhibitors (SSRIs) are more frequently prescribed than tricyclic antidepressants because of their less frequent side effects. Also the use of noradrenergic and specific serotonergic antidepressants (NaSSA) are increasing. These new antidepressants have characteristic side effect profiles in terms of gastrointestinal side effects, weight gain and sexual dysfunction which serve as direct cause of noncompliance. In the present study, we compared the drug side effects of patients with major depressive disorder who have taken either mirtazapine or SSRIs. METHODS: Among those patients who were treated at Department of Psychiatry, St. Mary's Hospital, The Catholic University of Korea, from Jun, 2002 to July, 2002, we included patients who met DSM-IV criteria for major depressive disorder. Patients who reveive either mirtazapine or SSRIs (fluoxetine, paroxetine) monotherapy as an antidepressant were enrolled. Patients with physical illnesses or poor drug compliance were excluded. A self-rating questionnaire was used to assess the drug side effects. RESULTS: Total 86 patients (mirtazapine;24, SSRIs;62 (fluoxetine 18, paroxetine 44)) were participated in this study. There was no difference at age (mirtazapine;48.0+/-14.0 years, SSRIs;43.3+/-15.6 years), sex ratio (mirtazapine;male 12: female 12, SSRIs;male 24: female 38), and mean duration of administration (mirtazapine;20.2+/-21.5 weeks, SSRIs;32.1+/-50.9 weeks) between two groups. Patients taking mirtazapine have significantly less side effects in terms of decreased appetite, yawn, decreased libido, and anorgasmia. Patients taking SSRIs have significantly less side effects in terms of peripheral edema than mirtazapine. CONCLUSION: Mirtazapine and SSRIs showed differences in some side effects. Mirtazapine showed more favorable side effect profiles in the gastrointestinal and sexual side effects than SSRIs. This data was thought to be useful guidelines in selecting antidepressants hereafter.

Monocyte Chemoattractant Protein-1(MCP1)-2518 Polymorphism and Major Depressive Disorder / 신경정신의학

OBJECT: This study was designed to examine the association between monocyte chemoattractant protein-1 (MCP1) -2518 polymorphism and major depressive disorder (MDD). METHODS: Ninety patients with MDD and 114 healthy controls participated in this study. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Genotype and allele distributions in patients with MDD were significantly different from those of the controls. In particular, subjects with the allele A were found to have an increased risk of MDD. CONCLUSION: The present study suggests that the MCP1 -2518 polymorphism may have a potential role for susceptibility to MDD in the Korean population and thus calls for consecutive studies in order to pile up the data with larger different ethnic background.