Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.

Amplification of distinct α-synuclein fibril conformers through protein misfolding cyclic amplification

Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease. Using a technique known as protein misfolding cyclic amplification, originally developed for amplifying prions, we established a procedure through which the amplification of α-synuclein fibrils is possible. With a trace amount of seeds, we succeeded in amplifying α-synuclein fibrils. The replication of the seeds was faithful in terms of conformation even after multiple rounds of cyclic amplification. Moreover, two transgenic mouse strains each representing a distinct synucleinopathy were used to investigate different conformers by using this technique. The amplified α-synuclein fibrils derived from the tissue extracts of these two strains led to the production of two different fibril conformers with distinct proteinase K digestion profiles. Together, our results demonstrated that a trace amount of α-synuclein fibrils in tissue extracts could be amplified with their conformations conserved. This procedure should be useful in amplifying α-synuclein fibrils from the brains and body fluids of patients afflicted with synucleinopathies and may serve as a potential diagnostic tool for Parkinson disease and other synucleinopathies.

Changes in the Clinical Manifestations of Ocular Injuries Induced by Power Lawn Mowers

PURPOSE: To investigate changes in the clinical manifestations of ocular injuries induced by power lawn mowers. METHODS: In a retrospective study of 172 patients with ocular injuries induced by power lawn mowers in 2006, 2010, and 2014. Best corrected visual acuity (BCVA) at the time of presentation and 6 months after trauma, age, sex and seasonal distribution were analyzed. We assessed the degree of injury using slit lamp biomicroscopy, fundus examination, and computed tomography and analyzed the prognoses according to open/closed injury and, anterior/posterior segment injury. All patients underwent medical or surgical treatment, and the factors affecting final BCVA were analyzed. RESULTS: The ratio of closed injuries increased significantly (p = 0.027), as did the ratio of corneal erosion (p = 0.020), and, the ratio of corneal laceration decreased significantly (p = 0.014) over time. In the multivariate analysis, initial BCVA was the only risk factor of poor visual outcome in both open and closed injuries. CONCLUSIONS: The proportion of open globe injury has decreased over time. In contrast, the proportion of simple injuries such as corneal erosion has increased in ocular injuries induced by power lawn mowers. Lower initial visual acuity was the only risk factor of poor visual outcome in both open and closed injuries.

Mechanism of Anti-α-Synuclein Immunotherapy

Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson's disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy.

Deep Vein Thrombosis in Patients with Pulmonary Embolism: Prevalance, Clinical Significance and Outcome

PURPOSE: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are considered as similar disease entities representing different clinical manifestations. The objectives of this study were: 1) to determine the prevalence and outcome of DVT in patients with PE; 2) to identify additional risk factors for PE-related unfavorable outcome and 30-day all-cause mortality; and 3) to establish the clinical importance of screening for concomitant DVT. MATERIALS AND METHODS: From January 2013 to December 2015, a total of 141 patients with confirmed PE were evaluated. The prevalence and outcome of DVT in patients with PE was determined. Furthermore, the potential risk factors for PE-related unfavorable outcome and 30-day all-cause mortality were also analyzed. RESULTS: The prevalence of concomitant DVT was 45.4%. PE-related unfavorable outcome was observed in 21.9% of all concomitant DVT, with all-cause mortality of 21.9%. There was no significant relationship between the presence of concomitant DVT and the development of PE-related unfavorable outcome or all-cause mortality. Our results indicated that heart rate >100/min and peripheral oxygen saturation <90% were independent predictors for PE-related unfavorable outcome. Regarding all-cause mortality, active malignancy and hypotension or shock were significant risk factors. CONCLUSION: Our findings demonstrate that approximately half of patients with PE possess DVT. However, this study failed to establish any clinical significance of concomitant DVT for PE-related unfavorable outcome and all-cause mortality. Tachycardia and hypoxemia were identified as significant predictors for PE-related unfavorable outcome along with active malignancy and hypotension or shock as significant risk factors of all-cause mortality.

The Efficacy of the Upright Position on Gastro-Esophageal Reflux and Reflux-Related Respiratory Symptoms in Infants With Chronic Respiratory Symptoms

PURPOSE: Gastro-esophageal reflux (GER), particularly non-acid reflux, is common in infants and is a known cause of chronic respiratory symptoms in infancy. Recent guidelines recommended empirical acid suppression therapy and the head-up position in patients with suspected GER. However, the efficacy of the upright position in relieving GER and reflux-related respiratory symptoms in infants is unclear. We conducted this study to investigate the efficacy of the upright position on GER and reflux-related respiratory symptoms in infants with chronic respiratory symptoms. METHODS: Thirty-two infants (21 male; median age, 5 months; range, 0 to 19 months) with unexplained chronic respiratory symptoms underwent multi-channel intraluminal esophageal impedance and pH monitoring. We retrospectively compared the frequencies of GER and reflux-related symptoms according to body position. RESULTS: A mean of 3.30 episodes of reflux per hour was detected. Overall, refluxes were more frequent during the postprandial period than the emptying period (3.77 vs. 2.79 episodes/hour, respectively; P=0.01). Although there was no significant difference in the total refluxes per hour between the upright and recumbent positions (6.12 vs. 3.77 episodes, P=0.10), reflux-related respiratory symptoms per reflux were significantly fewer in infants kept in an upright position than in a recumbent position during the postprandial period (3.07% vs. 14.75%, P=0.016). Non-acid reflux was the predominant type of reflux in infants, regardless of body position or meal time. CONCLUSIONS: The upright position may reduce reflux-related respiratory symptoms, rather than reflux frequency. Thus, it may be a useful non-pharmacological treatment for infantile GER disease resistant to acid suppressants.

Prevalence and Clinical Aspects of Sjogren Syndrome in Dry Eye Patients

PURPOSE: To investigate the prevalence and clinical aspects of Sjogren syndrome in patients who were diagnosed with dry eye syndrome in Korea. METHODS: The medical records of patients who were diagnosed with dry eye syndrome in a dry eye clinic during a 2-year period (March 2008 to March 2010) and were followed up for more than 3 months were reviewed retrospectively. RESULTS: A total of 206 patients were included in the present study. Fifty-eight patients (28%) had Sjogren syndrome and 39 patients (19%) showed primary Sjogren syndrome. Sjogren syndrome patients showed poorer results than non-Sjogren syndrome patients in ocular surface disease index score (OSDI), tear break up time, Schirmer test score, and ocular surface staining score using the Oxford scheme (p < 0.05). Among the patients with primary Sjogren syndrome, 27 patients were SSA (anti-Ro antibodies) or SSB (anti-La antibodies) positive and 12 patients were sero-negative. There were no statistically significant differences in objective or subjective parameters between the sero-positive and sero-negative groups. CONCLUSIONS: Sjogren syndrome was observed in 28% of all dry eye patients, in two-thirds of severe dry eye patients. Sjogren syndrome patients showed more severe clinical aspects than dry eye patients with non-Sjogren syndrome. Diagnosing Sjogren syndrome through systemic evaluation is necessary in the patients with severe dry eye.

Erratum: Continuous infusion of two doses of remifentanil immediately after laparoscopic-assisted vaginal hysterectomy (Korean J Anesthesiol 2010; 58(6): 537-541) / 대한마취과학회지

No abstract available.

Continuous infusion of two doses of remifentanil immediately after laparoscopic-assisted vaginal hysterectomy / 대한마취과학회지

BACKGROUND: We evaluated the effect and safety of the immediate postoperative continuous infusion of remifentanil at two doses in patients undergoing laparoscopic-assisted vaginal hysterectomy (LAVH) with alfentanil-based patient-controlled analgesia (PCA). METHODS: The study enrolled 50 ASA physical status 1 or 2 patients scheduled to undergo LAVH. Anesthesia was maintained with sevoflurane-remifentanil-air. At the last skin suture, the sevoflurane was discontinued, and patients were randomized to receive remifentanil 0.05 microgram/kg/min (group I) or 0.1 microgram/kg/min (group II). PCA was started at the time of eye opening and response to a verbal command. In the recovery room, we monitored the mean arterial blood pressure (MAP), heart rate (HR), respiratory rate (RR), SpO2, and bispectral index (BIS) at 5-minute intervals. Thirty minutes after starting PCA, the remifentanil was discontinued. Pain was assessed using a visual analog scale (0 = no pain; 100 = the worst possible pain) at 0, 5, 10, and 30 minutes after stopping the remifentanil infusion. RESULTS: The eye opening time, BIS, MAP, and HR did not differ significantly between the two groups, and pain scores were similar between the two groups. Respiratory depression (SpO2 < 90% or RR < 8/min) did not occur in group I but did occur in three patients in group II. CONCLUSIONS: Continuous remifentanil infusion (0.05 microgram/kg/min) immediately postoperatively with alfentanil-based PCA had a similar effect as a 0.1 microgram/kg/min infusion with respect to pain control without side effects. However, special attention must be given to respiratory depression.

Long-Term Results of Descemet's Stripping Automated Endothelial Keratoplasty in Korea

PURPOSE: To evaluate the long-term results of Descemet's stripping automated endothelial keratoplasty in Korea (DSAEK). METHODS: Seven patients with bullous keratopathy who underwent DSAEK and who were followed-up for more than 18 months were reviewed retrospectively. Best corrected visual acuity, refraction, corneal thickness, and endothelial cell count were examined before and after surgery. RESULTS: The mean follow-up period was 19.9 +/- 2.9 months (18 to 24 months), and the mean age was 61.42 +/- 10.13 years (46 to 76 years). Six patients (85.7%) showed successful results after surgery. Best corrected visual acuity (logMAR) was significantly improved from 1.62 (median) to 1.15 (median) (p = 0.027) at one month after surgery and was maintained until the final follow-up period. There were no statistical differences in spherical ametropia or astigmatism before or 18 months after the operation. Graft failure was observed in one case, in which penetrating keratoplasty was performed 12 months after DSAEK. CONCLUSIONS: Long term results of DSAEK showed fast visual recovery, low ametropia and astigmatism. DSAEK may be a good option for the surgical management of corneal endothelial disease.

Recurrent spinal myoclonus after two episodes of spinal anesthesia at a 1-year interval: A case report / 대한마취과학회지

Spinal myoclonus is an unusual, self-limiting, adverse event that may occur during spinal anesthesia. The exact cause and underlying biochemical mechanism of spinal myoclonus remain unclear. A few cases of spinal myoclonus have been reported after administration of intrathecal bupivacaine. We report a case in which spinal myoclonus recurred after two episodes of spinal anesthesia with bupivacaine at a 1-year interval in a 35-year-old woman. The myoclonus was acute and transient. The patient recovered completely, with no neurologic sequelae.

Comparison of Frequency Doubling Technology Perimeter and RNFL Photography for Early Diagnosis of Glaucoma

PURPOSE: To compare the frequency doubling technology perimeter (FDT) with retinal nerve fiber layer (RNFL) photography as a tool for the early detection of glaucoma. METHODS: Ninety-eight eyes of 98 patients were evaluated over a period of 3 months. According to the results of RNFL photography and FDT, Patients were divided into four groups based on the results of RNFL photography and optical coherence tomography (OCT). A comparison of the RNFL thickness of each group was performed using the OCT results. RESULTS: RNFL thickness in the group with abnormal FDT and normal RNFL were significantly decreased from those in the group with normal FDT and RNFL photography at the 6, 7 and, 10 o'clock area (p<0.05). CONCLUSIONS: There were statistically significant differences in the RNFL thickness between the group with abnormal FDT and normal RNFL photography, and the group with normal FDT and RNFL photography within the limited areas. These results imply that FDT is more useful for the early detection of glaucoma than RNFL photography.

A case of congenital syphilis mistaken for possible child abuse / 소아과

We describe the case of a 4-month-old male infant diagnosed with early congenital syphilis during evaluation of a left distal humerus fracture. This report emphasizes the importance of screening for syphilis among pregnant women and newborns, and is a reminder of the continued existence of congenital syphilis.

A Case of Rectus Muscle Transposition With Silicone Band in Strabismus Fixus With High Myopia

PURPOSE: To present a surgical result of rectus muscle transposition with silicone band without suture on the sclera in strabismus fixus with high myopia. CASE SUMMARY: A 73-year-old female patient with a 20-year history of bilateral esotropia and hypotropia visited our clinic. The patient`s right eye was aphakic because crystalline lens removal was performed 17 years earlier and the left eye was phthisical after retinal detachment, due to high myopia. Ocular movements in both eyes were severely restricted in all directions with the cornea barely visible. Ultrasound examination revealed posterior staphyloma of the retina. The axial length measurement was 32 mm in the right eye, and could not be measured in the left eye. Posterior tenon fixation of the medial rectus and inferior rectus muscle tendon was performed, in addition, fixation of the lateral half of the superior rectus and superior half of the lateral rectus muscle on the silicone band 10 mm posterior to each muscle's scleral insertion as a transposition procedure was performed. At 6 months postoperatively, there was no residual esotropia or hypotropia. The right eye maintained a gaze limitation but improved abduction and supraduction. CONCLUSIONS: In strabismus fixus with high myopia, posterior tenon fixation and muscle transposition with silicone band is an effective method without complication.

Clinical Aspects of Functional Articulation Disorder

PURPOSE: Speech and language development is an useful indicator of the overall development of children. Since speech and language delay can lead to emotional, social, and learning problems, the early intervention is very important. We examined 137 children with speech or language problems including 22 children of functional articulation disorders of their clinical features. METHODS: 137 children with speech or language problems in the Department of Pediatrics, Uijeongbu St. Mary's Hospital from January 2004 to December 2007 were reviewed for sex, age, developmental and language test findings retrospectively. Especially, in 22 children diagnosed with functional articulation disorders, articulation test findings were analyzed. RESULTS: 1) The mean age of 137 children was 46.8 months, the ratio of male to female was 2.5:1, and the most frequent age group was 24-35 months. The chief complaints included language delay(67.2%), mispronouncing speech sound(27%), stuttering(3.6%), learning disability(2.2%). The diagnoses of them were developmental language disorder(70.8%), functional articulation disorders(16.1%), mental retardation(5.8%), stuttering(2.9%), tongue tie(0.7%), normal language pattern(3.6%). 2) The mean age of 22 patients with functional articulation disorders was 63 months, the ratio of male to female was 1.4:1, and the most frequent age group was 60-71 months. The mean percentage of consonant correct of Picture Consonant Articulation Test was higher in older age group. In the types of phonetic errors substitutions were most common. Distortions, omissions, and additions were followed in the order of frequency. Substitutions and distortions were common in word initial and medial but omissions in word final. It is appeared that the patients had the difficulties in pronouncing alveolar fricative, palatal affricate, liquid, and velar plosive which mature lately in older children. Mainly palatal affricate, alveolar fricative, and velar plosive were substituted for alveolar plosive and the liquid and alveolar fricative were distorted as gliding. CONCLUSION: Categorizing the cause of language and speech delay is essential to make an adequate treatment plans and decrease the late complications. The future studies for the early screening, more suitable tests in Korean, treatment guidelines or prognosis are needed.

Vascular Thoracic Outlet Syndrome with Arterial Occlusion: A case report

The diagnosis of thoracic outlet syndrome (TOS) is sometimes confused by its nonspecific symptoms and various etiologies. Moreover, the paths of involving nerves and arteries are highly diverse. We report a 35 year-old man who had numbness and coldness in his left upper extremity with no improvement to medical therapy. The electrophysiologic studies were normal. Radial artery pulse was absent and the thermography revealed markedly reduced temperature below the left mid-forearm. The arteriography showed compression of the left subclavian artery between the clavicle and the 1st rib with aneurysmal change proximal to the compression. Occlusion of the left brachial artery and collateral arteries were also observed. Under the diagnosis of vascular TOS, 1st rib resection was performed and his symptoms were relieved. Vascular TOS may be considered in cases of upper limb paresthesia.

A Case of Atypical Fundic Gland Hyperplasia Confirmed by Endoscopic Mucosal Resection / 대한소화기내시경학회지

Fundic gland hyperplasia is a hyperplasia of glandular portion on epithelium of gastric fundus or body. The incidence of fundic gland hyperplasia is 1.4% in the general population. Fundic gland hyperplasia is the most common cause of multiple polyposis. Probably the most cause of fundic gland hyperplasia is a hamartomatous origin but some hyperplastic origin because of spontaneous remission. We have experienced and reported a case of atypical fundic gland hyperplasia confirmed by endoscopic mucosal resection.

Coverage of Donor Site Defect of Radial Forearm Free Flap by using Terudermis(R)

Split-thickness skin grafting is commonly used to cover donor site defect of radial forearm free flap. One of disadvantages in this method is contour reflection of underlying structures (tendons and muscles) with irregularity which was caused by incomplete soft tissue replacement, and we called it 'silhouette phenomenon'. To promote soft tissue replacement, we have used Terudermis(R) (atelocollagen). In 10 cases of radial forearm free flap surgery of 10 patients, Terudermis(R) was applied on flap donor site just after flap surgery, followed by split-thickness skin grafting for resurfacing after 2 weeks. In all cases, Terudermis(R) and skin graft were taken well with no complications such as skin necrosis and loss. We successfully overcame silhouette phenomenon in all cases in the follow-up period of mean 8 months. Terudermis(R) , as a tissue-restoring biomaterial, is expected to be easily used for coverage of donor site defect of radial forearm free flap.

Modification of Le Fort III Osteotomy and Fronto-orbital Advancement for the Correction of Crouzon's Disease

In 1912, Crouzon reported one of craniofacial dysostosis, which was inherited as an autosomal dominant trait and characterized by craniosynostosis, midface hypoplasia, and exorbitism. In 1950, the first midface advancement was performed by means of a total facial osteotomy by Sir Harold Gillies. In 1967, Tessier accomplished complete craniofacial dysjunction by performing Le Fort III-Tessier I osteotomy on the basis of Le Fort III fracture and laid the foundation for modern craniofacial surgery. Variable combinations of the surgeries and osteotomies are performed considering functional disabilities as well as patient's age, general condition, and aesthetic problems. The nineteen-year-old female patient complained of frog-like face and showed severe exorbitism and midface hypoplasia, while the occlusion, being relatively normal. We applied modified Le Fort III osteotomy and fronto- orbital advancement. Over the follow-up period of six months, her previous normal occlusion was preserved and the exorbitism and midface deformity largely improved aesthetically.

A comparisin of the Operative Results and Costs Between Interosseous Wiring and Miniplate Fixation in Open Reduction of Mandible Fracture

Mandible fractures have recently been managed by rigid internal fixation with miniplate and screws more often than by traditional interosseous wiring methods. The purpose of this paper was to compare traditional interosseous wiring with miniplate fixation in open reduction of mandible fracture, especKweonially in operative results and costs. From June of 1989 to June of 1998, there were 142 patients, admitted to the department of Plastic and Reconstructive Surgery, Chun-Cheon Sacred Heart Hospital, Hallym University. Of those, 101 patients were managed by open reduction, and among them, 83 patients were treated with miniplate fixation, but 18 patients had recently been treated with interosseous wiring methods. No significant difference was noted between the two groups in terms of complications, but the overall cost of miniplate and screws was higher than interosseous wiring, while the mean operative time was longer in the group treated with miniplate fiation. The authors recommend interosseous wiring technique for patients with mandible fractures requiring open reduction and fixation, except for absolute indications of rigid internal fixation.