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Rationale: Osteochondral lesions on the lateral process of the talus involving the subtalar joint are rare; the optimal surgical treatment remains to be clarified as there are few reports. Additionally, bilateral cases are extremely rare. Therefore, the clinical outcomes of the surgical treatment for bilateral osteochondral lesions on the lateral process of the talus involving the subtalar joint have not been fully elucidated., Patient Concerns: A 16-year-old boy who played soccer presented to our hospital with bilateral hindfoot pain. The symptoms persisted even after 3 months of conservative treatment. The patient and family requested surgical treatment to relieve the symptoms., Diagnoses: The patient was diagnosed with bilateral osteochondral lesions on the lateral process of the talus, involving the subtalar joint based on computed tomography and magnetic resonance imaging findings., Interventions: Arthroscopic debridement and microfracture were performed bilaterally., Outcomes: Postoperative computed tomography and magnetic resonance imaging of both feet revealed remodeling of the subchondral bone. The patient returned to play at the pre-injury level with no pain., Lessons: This report describes a case of bilateral osteochondral lesions on the lateral process of the talus, involving the subtalar joint. Arthroscopic debridement and microfracture were effective in relieving symptoms and the subchondral bone remodeling. To the best of our knowledge, this is the first report of arthroscopic treatment of osteochondral lesions of the lateral process of the talus involving the subtalar joint., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Prevalence of impaired foot function among baseball players with and without a disabled throwing shoulder/elbow was investigated. The study included 138 male players. Players who had previously complained of shoulder/elbow pain during throwing motion were defined as the players with a history, and those who experienced shoulder/elbow pain during the examination were defined as having the injury. Foot function was evaluated by foot "rock paper scissors" movements and floating toes. Their prevalence was assessed and the relationships between players with and without the injuries were statistically analyzed. The prevalence of players with a history and injury was 27% and 7%, respectively. The prevalence of impaired foot function on the non-throwing side among players with injury was significantly higher than those without (60% vs. 28%, P < 0.001) and higher tendency on the throwing side than those without (60% vs. 32%). Regarding floating toes, players with a relevant history showed a significantly higher prevalence on the throwing side than those without (49% vs 28%, P < 0.001) and higher tendency on the non-throwing side than those without (49% vs 32%). Players with disabled throwing shoulder/elbow have a significantly higher prevalence of impaired foot function and floating toes than players without it., (© 2024. The Author(s).)

Introduction: Patients with total knee arthroplasty occasionally develop postoperative abnormalities such as posttraumatic knee stiffness and arthrofibrosis, which may affect activities of daily living. However, there are no clear assessment methods or interventions for knee stiffness. Musculoskeletal ultrasound imaging enables real-time evaluation of mobility and flexibility of tissues. The purpose of this case report was to describe the use of musculoskeletal ultrasound imaging for evaluating the optimal location and methods of passive manipulation., Case Description: The patient was an 82-year-old woman who had undergone total knee arthroplasty. She was unable to climb stairs due to limited knee flexion. Based on the results of musculoskeletal ultrasound imaging assessment, we hypothesized that the knee flexion limitation was caused by decreased sliding movement of the suprapatellar pouch. Hence, we performed passive manipulation on the tissue with decreased sliding under musculoskeletal ultrasound guidance., Outcomes: The patient's knee flexion angle increased from 90° to 110° within 1 week of intervention, and her gait speed improved from 16.48 to 13.2 s per 10 m. Furthermore, after the intervention, she was able to climb 10 steps using a handrail., Discussion: Ultrasound imaging is important because it allows the examination of tissues with mobility changes such as in arthrofibrosis. Our work highlights the use of musculoskeletal ultrasound imaging for identifying the target region for therapy and for providing guidance during passive manipulation.

Background: Floating toes are a condition and deformity in which some of the toes are afloat. Many functional impairments in floating toes have been previously studied lately and several factors related to floating toes have also been reported. However, no reports have considered the relationship between lifestyle and floating toes among children. The purpose of this study was to reveal the prevalence of floating toes among school children and reveal its relationship with lifestyle., Methods: In total, 138 young male baseball players were recruited. Lifestyle was evaluated by using a questionnaire and chosen whether the main lifestyle was Japanese or Western, if the bedding was futons or beds, and if the toilet was Japanese style (a squat toilet) or Western style. Floating toes were defined as toes that were not in contact with the mat. Ankle dorsiflexion in the knee-flexed and knee-extended positions was measured in a weight-bearing position. The relationship between the floating toes and lifestyles, and the comparison of ankle dorsiflexion range of motion between the lifestyles were statistically analyzed., Results: Players living in a Western style showed a significantly higher prevalence of floating toes on both feet compared with the players living in a Japanese style (throwing side; 39% vs. 19%, p = 0.04, and non-throwing side; 43% vs. 19%, p = 0.01). Players living in a Western style with beds showed a significantly smaller range of motion on both sides of ankle dorsiflexion in the knee-flexed position compared with those who were not (throwing side; 37.2 ± 5.7° vs. 39.0 ± 6.6°, p = 0.04, and non-throwing side; 36.8 ± 5.8° vs. 38.6 ± 6.1°, p = 0.04)., Conclusion: Children mainly living in a Western lifestyle showed a significantly higher prevalence of floating toes on both feet compared to those mainly living in a Japanese lifestyle. The prevalence of floating toes may be related to lifestyles among children., Trial Registration: The study was approved by the institutional review board of the Waseda University Graduate School of Sport Sciences (IRB number 2021-185)., (© 2023. The Author(s).)

The prevalence of impaired foot function and floating toes of 91 baseball players with disabled throwing shoulder or elbow were retrospectively investigated. Foot function was evaluated by foot "rock paper scissors" and floating toes were confirmed if none of the toes made contact with the mat in standing posture. The prevalence of impaired foot function and floating toes and the relationship between between them were determined. Abnormal foot function was observed in 83 players (91%); of those, 73 players (88%) also had floating toes, and the prevalence was statistically significant compared to those without it (12%) ( P < 0.001). Floating toes were observed in 74 players (81%); of those, 73 players (99%) had impaired foot function, and the prevalence was also statistically significant compared to those without them (59%) ( P < 0.001). Baseball players with disabled throwing shoulder or elbow have high rates of impaired foot function and floating toes.

Background: Changes in soft-tissue structures such as anterior laxity and posterior tightness are thought to contribute to the development of pathologic internal impingement in baseball players. Although side-to-side differences in shoulder rotational range of motion (ROM) is commonly used in clinical practice to quantify the soft-tissue changes, the ROM does not accurately reflect the soft-tissue changes because the ROM is affected not only by the soft tissues, but also by the bone. Increased retroversion of the humeral head is often observed in the dominant shoulder of throwing athletes. The purpose of this study was to determine the relationship between the soft-tissue-related (STR) ROM and pathologic internal impingement in baseball players., Methods: Bilateral humeral retroversion and ranges of glenohumeral external rotation (ER) and internal rotation (IR) were investigated in 81 high-school baseball players. The players were divided into two groups: the internal impingement group (19 players) and the control group (62 players). Humeral retroversion was measured using the ultrasound-assisted technique to assess the bone-related ER and IR. The STR ER and IR were defined as subtracting the amount of humeral retroversion from the measured ER and IR., Results: The side-to-side difference (throwing shoulder - nonthrowing shoulder) in humeral retroversion showed no significant difference between the internal impingement group (6° ± 10°) and control group (11° ± 11°) (P = .064). The side-to-side difference in STR ER was significantly greater in the internal impingement group (12° ± 12°) than that in the control group (1° ± 14°) (P = .002). No significant difference was observed in the side-to-side difference in STR IR between the internal impingement group (-7° ± 16°) and control group (-5° ± 15°) (P = .696). Pathologic internal impingement was significantly associated with the side-to-side difference of STR ER (odds ratio, 1.06 for increase of 1°; 95% confidence interval, 1.02-1.11; P = .008)., Conclusion: In high-school baseball players, the increased STR ER in the throwing shoulder may be associated with pathologic internal impingement. An increase of 10° in side-to-side difference in STR ER would increase the risk of pathologic internal impingement by 1.8 times., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Aim: Although the football goalkeepers are overhead athletes, no studies have reported the prevalence of disabled throwing shoulder (DTS) and the shoulder function. Thus, this study aimed to investigate the prevalence of DTS among youth football goalkeepers and to determine the relationship among their shoulder functions., Methods: Youth football goalkeepers, who participated in a pre-participation medical examination were included in the study. The questionnaire was handed out before the examination to determine the players' age, dominant hand, and shoulder pain history. If the player had a history of shoulder pain during ball throwing motion in the past, they were defined as goalkeepers with DTS. Physical examination of scapular positioning, scapular retraction and rotator cuff muscle strength, and ultrasonographic evaluation were performed., Results: Six goalkeepers (16%) had a history of DTS among the 38 male youth football goalkeepers. The presence of scapular malpositioning, limitation of scapular retraction, and decrease in rotator cuff strength was significantly higher in goalkeepers with DTS than in those without DTS ( p  = 0.03, p  < 0.001, p  < 0.001, respectively). Three goalkeepers with DTS revealed ultrasonographic findings., Conclusion: The prevalence of DTS among youth football goalkeepers was 16%. All these players had scapular malpositioning and limitation of scapular retraction. Scapular malpositioning and limitation of scapular retraction may be related to the DTS in youth football goalkeepers., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest. The authors, their immediate families, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this title., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Adolescent DanceSport athletes who regularly dance in high heels have a higher possibility of developing hallux valgus deformity and foot pain. We believe that the occurrence of foot disorders may change the loading on their feet, which thus affects the athletic performance of those adolescents., Methods: A total of 63 adolescent DanceSport athletes (16 boys, 47 girls) were included. The plantar pain in the first metatarsophalangeal (1st MTP) joint was evaluated using a questionnaire, and the hallux valgus angle was evaluated using digital photographs (HVAp). The loading values of the plantar pressure while performing relève on demi-pointe were measured using sensor sheets. The participating boys and girls were analyzed separately., Results: The results showed that female adolescent DanceSport athletes with the 1st MTP joint plantar pain showed a decrease in the loading distribution and plantar pressure percentage on the hallux and an increased loading distribution and pressure distribution of the metatarsal head as the HVAp increased., Conclusion: Among adolescent DanceSport athletes with plantar pain in the 1st MTP joint and a large HVAp, the loading manner of the foot may have changed, which may be associated with a decrease in the toe function and performance.

Relationship between sports and spondylolysis fracture angle (SFA), and hip internal rotation range of motion (IR ROM) between the sports groups among athletes with spondylolysis were investigated. Sports requiring repeated rotation of the trunk and hips during most aspects of the activity was defined as rotation-related sports (RRS). The SFA was defined as rotation-type or horizontal-type by using the axial view of the CT scan. Percentage of rotation type and SFA of the non-dominant side for RRS group was significantly greater than those of non-RRS group. Hip IR ROM of RRS group was significantly smaller than that of non-RRS group., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest. The authors, their immediate families, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this title., (© 2021 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: The relationship between the results of the Star Excursion Balance Test (SEBT) and lateral ankle sprain (LAS) among youth football players was investigated., Methods: The dominant leg and history of LASs were asked from 33 male youth football players. The SEBT in the anterior, posterolateral, and posteromedial directions were measured for both limbs. The relationship between the history of LAS and reach difference over 4 cm between the dominant and nondominant legs in each direction was statistically analyzed., Results: The number of players with the history of LAS, whose dominant/nondominant reach difference was over 4 cm in the anterior direction, was significantly higher to that in players without a history of LAS in both the dominant (94% vs. 63%, p = 0.02) and nondominant (100% vs. 25%, p = 0.02) legs., Conclusion: Youth football players with a history of LAS showed reach deficit in the anterior direction in the SEBT., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Background: Loop diuretics are used to manage fluid retention in patients with end-stage kidney disease undergoing hemodialysis (HD). This randomized, double-blind, placebo-controlled, Phase 2 trial evaluated the efficacy and safety of tolvaptan, a vasopressin V2 receptor antagonist, in Japanese HD patients., Methods: A total of 124 patients (24-h urine volume ≥500 mL) on thrice-weekly HD were randomized to receive oral tolvaptan 15 mg/day (n = 40), tolvaptan 30 mg/day (n = 40) or placebo (n = 44) for 24 weeks. Efficacy endpoints were change from baseline in 24-h urine volume, total fluid removal by HD per week and interdialytic weight gain (IDWG). Safety was assessed via the incidence of treatment-emergent adverse events (TEAEs)., Results: At treatment end, the difference (95% confidence interval) from the placebo group in the mean change from baseline in 24-h urine volume was significant in the tolvaptan 15 mg {429.1 mL [95% confidence interval (CI) 231.0, 627.2]; P < 0.0001} and 30 mg [371.6 mL (95% CI 144.1, 599.2); P = 0.0017] groups. The mean changes from baseline in total fluid removal by HD and IDWG were not significantly different in the tolvaptan groups versus the placebo group. Although the proportion of patients with TEAEs was lower in the placebo group (77.3%) than in the tolvaptan groups (92.3%), tolvaptan was safe and well-tolerated during the study period., Conclusions: Tolvaptan significantly sustained diuretic action for 24 weeks in HD patients but did not reduce total fluid removal by HD per week and IDWG to the same extent., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Medial open wedge high tibial osteotomy (OWHTO) is usually performed with proximal tuberosity osteotomy or setting the osteotomy line proximal to the tuberosity. However, OWHTO can result in patellofemoral complications due to postoperative patella infera. A new OWHTO technique, biplanar osteotomy with a distal tuberosity osteotomy, was reported in 2004 to prevent postoperative patella infera. To ensure that the 2 osteotomy lines maintain perpendicular, we describe the OWHTO procedure with a distal tuberosity osteotomy technique using a TriS Medial HTO Plate System (Olympus Terumo Biomaterials Corp., Tokyo, Japan) and a right angle guide we developed. In this Technical Note, we describe the procedure and advantages, risks, and limitations, as well as the pearls and pitfalls based on our experience., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier.)

Background: Pitch velocity is associated with elbow injuries among skillful baseball players. However, the relationship between pitch velocity and throwing elbow injuries among youth players has not yet been clarified., Purpose: To investigate the influence of pitch velocity on medial elbow pain and medial epicondyle abnormality among youth baseball players., Study Design: Cohort study; Level of evidence, 3., Methods: The participants consisted of 256 elementary school players (mean age, 11 ± 1 years; range, 9-12 years). The medial aspect of the elbow was evaluated using ultrasound imaging. A questionnaire was used to investigate past or present pain in the elbow, background of the players (age, height, body mass index, and years of baseball experience), and playing environment (number of days of practice in a week, experience as a pitcher, and cryotherapy of the shoulder and elbow after practice). Positioning of the scapula, range of motion in shoulder internal/external rotations and hip internal rotation, angle of the straight-leg raise, and heel-to-buttock distance were measured. The pitch velocity was recorded using a pitch velocity radar gun. The relationship between these variables and the presence of medial epicondyle abnormality, as well as past or present elbow pain, were statistically analyzed., Results: A medial epicondyle abnormality was observed in 130 players (51%), elbow pain in the past in 65 players (25%), and elbow pain during the examination in 14 players (5%). Sixty-nine players (27%) experienced elbow pain either in the past or during examination. Abnormality of the medial epicondyle had a relationship with the pitch velocity (odds ratio [OR], 1.1 for increase of 1 km/h; 95% CI, 1.1-1.2; P < .0001) and the number of practice days in a week (OR, 1.8 for increase of the practice days; 95% CI, 1.4-2.5; P < .0001). Pitch velocity was also significantly related with past pain, present pain, and past and/or present pain of the elbow (OR [km/h], 1.1, 1.1, 1.1; 95% CI, 1.0-1.1, 1.0-1.2, 1.1-1.2; P < .0001, P = .002, P < .0001, respectively)., Conclusion: Pitch velocity was significantly associated with abnormality of the medial epicondyle and elbow pain. A 10-km/h increase in pitch velocity would increase the risk of medial epicondyle abnormality and medial elbow pain by 3 times.

Background: In the treatment of head and neck cancer, severity of chemoradiotherapy-induced oral mucositis has been recognized as one of the key factors affecting the outcomes of the anticancer therapies. Therefore, the development of treatments mitigating oral mucositis would be of clinical significance, although the adequate assessment procedure for efficacy evaluation remains to be established. We conducted this post hoc study to assess the effect of objective evaluation of the severity grade on the outcomes of the clinical trial., Methods: In the original trial with rebamipide liquids (0, 2, and 4%) for chemoradiotherapy-induced oral mucositis, the investigators in local sites and independent central review separately determined the severity grades in accordance with Common Terminology Criteria of Adverse Events version 3.0 based on the Assessment Sheet scored by the investigators. The discordance in severity grades between the investigators and central review was analyzed on cross table., Results: The analysis revealed the discordance rate over the trial was 34%. While the incidences of severe oral mucositis in the placebo, rebamipide 2%, and 4% groups evaluated by the central review were 39%, 29%, and 25%, respectively, the respective values in the investigator's evaluation were 32%, 39%, and 44%., Conclusion: In the clinical trial for the treatment of oral mucositis, it was strongly suggested that objective evaluation with a consistent scale would be required.

Pullout tests to determine the effect of anchor threads on the pullout strength was conducted by using universal testing machine, synthetic cancellous bone and thread-less metallic anchor. Anchors were inserted at 45°, 90° or 135° from the surface and they were pulled at 45° from the surface. The maximum load to failure was compared among the 3 insertion angles. Pullout strength of the anchors inserted at 45° was significantly greater than those inserted at 90° or 135°. Pullout strength of the thread-less anchor was the greatest when it was inserted at 45° to the bone surface., Level of Evidence: level II.

Purpose: To investigate the minimum distance between the anchors without decreasing the pullout strength using the polyurethane foams and the porcine bones., Methods: Metal screw-type anchors and PEEK (polyether ether ketone) coil-type anchors were used. Two same-type suture anchors were placed into the polyurethane foams and porcine bones. The polyurethane foams were 3 different densities simulating severe osteoporosis, osteoporosis, and normal bone. The distances between the centers of anchors were set at 4, 6, 8, and 10 mm. The pair of anchors were loaded to failure if they had not been pulled out after cyclic loading from 50 to 200 N, 10 cycles per each 50-N increment. Mode of failure, ultimate load to failure, displacement of the anchor, and number of cycles completed were recorded., Results: In all polyurethane foams of 3 different densities with use of metal screw-type anchors, the 4-mm group demonstrated a significantly lower ultimate load to failure compared with the 6-, 8-, and 10-mm groups (P < .01). There were no significant differences in the load to failure among the 6-, 8-, and 10-mm groups. Porcine bone or PEEK coil-type anchor showed results similar to those of the metal screw-type anchors., Conclusion: For the 2 tested anchors, the minimum distance between the anchors without decreasing the pullout strength was 6 mm (center to center) regardless of bone density in a biomechanical study., Clinical Relevance: Although it has been thought that the minimum distance between the anchors without decreasing the pullout strength was 1 cm (center to center), our data showed that it was 6 mm., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Backgrounds: There have been many reports describing that the capsular fibrosis of the shoulder joint is the main cause of frozen shoulder, whereas others reported the significance of subacromial impingement as an etiological factor. The purpose of this study was to investigate the contact pressure between the coracoacromial arch and the rotator cuff tendons to clarify the contact phenomenon in shoulders with joint contracture., Methods: Fourteen fresh-frozen cadaveric shoulders were used. Specimens were divided into two groups: normal group (8 shoulders, definition: more than 61° of flexion and abduction and more than 21° of external rotation) and joint contracture group (6 shoulders, definition: less than 60° of flexion and abduction and less than 20° of external rotation). Contact pressure and area beneath the coracoacromial arch were measured by a flexible force sensor during flexion, abduction, internal and external rotation in adduction and abduction, extension and horizontal extension motions., Results: The peak contact pressure under the acromion was observed at 90° in flexion and abduction in the normal group, whereas that in the contracture group was observed at 30° in flexion (P = 0.037) and at 30° in abduction (P = 0.041). Contact pressure in the contracture group was significantly higher than that in the normal group at 20° and 30° of abduction (P = 0.043, P = 0.041, respectively). There were no significant differences of contact pressure during other motions. Although no significant differences of contact pressure beneath the coracoacromial ligament were observed, contact area significantly increased in extension and horizontal extension motion., Conclusion: The contact between the acromion and the rotator cuff was observed in lower angles of flexion and abduction in shoulders with contracture than in those without. When treating patients with shoulder contracture, we need to perform rehabilitation taking such an abnormal movement into consideration., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

American Indian and Alaska Native (AI/AN) veterans living in rural areas have unique health care needs and face numerous barriers to accessing health care services. Among these needs is a disproportionate prevalence of posttraumatic stress disorder and other mental illnesses. Since 2001, 14 rural communities have partnered with the U.S. Department of Veterans Affairs and the Centers for American Indian and Alaska Native Health at the University of Colorado Anschutz Medical Campus to extend telemental health clinics to American Indian veterans. Administrative and, to some extent, clinical considerations of these clinics have been reviewed previously. This paper describes a model of care, evolved over a 14-year period, that weaves together evidence-based Western treatment, traditional Native healing, and rural Native communities into 4 main components: mental health care, technology, care coordination, and cultural facilitation. We delineate improvements to care made by addressing barriers such as system transference, provider-patient trust, and videoconferencing. Similarly, the discussion notes ways that the care model leverages strengths within Native communities, such as social cohesion and spirituality. Future steps include selection of appropriate performance indicators for systematic evaluation. The identification of key constructs of this care model will facilitate comparisons with other models of care in underserved populations with chronic and complex health conditions, and eventually advance the state of care for our warriors. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: How the use of the transosseous-equivalent (TOE) technique effects the stress concentration in repaired rotator cuff tendon is unknown. This study was conducted to determine the strain between the intact rotator cuff tendon and the tendon repaired using the TOE technique with and without medial row suture tying., Materials and Methods: Strain of the infraspinatus tendon from 10 fresh-frozen cadavers was measured at the (A) tendon insertion, (B) tendon footprint, (C) tendon of the medial suture level, and (D) musculotendinous junction of the tendon. The strain was measured during 2 cycles of internal and external rotations while applying 4 different loads to the infraspinatus. After the intact tendon was evaluated, an artificially created tear of the infraspinatus was repaired using the TOE technique. Medial row sutures were tied in 5 shoulders (T group) and untied in the rest (UT group). The strains at 4 sites were compared between the intact and the TOE-repaired tendon and between the T and UT groups., Results: The strain was significantly reduced at site B in the repaired tendon in the T and UT groups compared with the intact tendon for all loads ( P  < .05). At site C, the strain increased for all loads in the T group compared with the intact tendon ( P  < .05)., Conclusion: The strain of the tendon over the footprint area was significantly smaller than the intact tendon when repaired with the TOE technique. The strain at the medial suture level was significantly greater when the medial sutures were tied compared with those untied.

Background: The relationship between the disabled throwing shoulder and humeral retroversion has recently attracted a great deal of attention. However, none of the previous studies clarified when the side-to-side difference of humeral retroversion in young baseball players would start. This study aimed to clarify when the difference of humeral retroversion in the dominant and nondominant sides appeared in baseball players., Methods: The bicipital-forearm angle in bilateral shoulders of 172 elementary school baseball players was measured by ultrasound. The bicipital-forearm angle was defined as an angle between the perpendicular line to the bicipital groove and the ulnar long axis with the elbow flexed at 90°. The correlation between the bicipital-forearm angle and the grade and the difference of the bicipital-forearm angle between the dominant and nondominant sides were analyzed., Results: In the nondominant shoulders, the bicipital-forearm angle increased with the grade in school (r = 0.32, P < .0001), but this was not observed in the dominant shoulders. In the fourth to sixth graders, the bicipital-forearm angles were significantly smaller in the dominant shoulders than in the nondominant shoulders., Conclusion: Our findings indicated that humeral retroversion decreased with age in the nonthrowing side but not in the throwing side and that the side-to-side difference of humeral retroversion in the baseball players became obvious from the fourth grade. We assume that the repetitive throwing motion restricts the physiologic humeral derotation process and the difference became apparent from the fourth grade when the growth spurt begins in boys., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to compare the pullout strength of anchors inserted at 90° and 45° to the bone surface using synthetic bones and porcine humeri., Subjects and Methods: Pullout tests were performed by universal testing machine. Synthetic cancellous bones of 0.08, 0.16, and 0.24 g/cm 3 (defining as low, medium and high density, respectively) with 2-mm-thick cortical bone model attached on one side and the greater tuberosity of porcine humeri (average bone density, 270 mg/cm 3 ) were chosen for pullout tests. Metallic anchors were inserted at 90° or 45° to the surface and pulled at 90° or 45° from the surface. The maximum load to failure for each condition was recorded. Differences in pullout failure loads between insertion angle, pulling angle, and bone density were analyzed., Results: When the sutures were pulled at 90° in low, medium, high density bones, and porcine humeri, 90°-inserted-anchors showed higher pullout strength than the 45°-inserted-anchors (534.6 ± 28.9 N vs. 488.1 ± 25.3 N (p < 0.05), 636.8 ± 25.3 N vs. 517.5 ± 27.4 N (p < 0.01), 735.6 ± 45.1 N vs. 557.0 ± 42.5 N (p < 0.01), and 285.6 ± 47.2 N vs. 181.4 ± 31.3 N (p < 0.01), respectively). When the sutures were pulled at 45° in low, medium density bones and porcine humeri, 90°-inserted-anchors showed higher pullout strength than the 45°-inserted-anchors (651.1 ± 38.3 N vs. 529.4 ± 37.6 N (p < 0.01), 711.4 ± 25.3 N vs. 599.2 ± 29.8 N (p < 0.01), and 265.3 ± 49.0 N vs. 181.5 ± 29.4 N (p < 0.01), respectively)., Conclusion: Pullout strength of the anchors inserted at 90° to the bone surface was greater than the anchors inserted at 45° regardless of the bone density., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to investigate the association between acromioclavicular (AC) joint pain and superior capsular bulging assessed by ultrasound in adolescent baseball players., Methods: One hundred and fifty players (1st-8th graders) were examined. All subjects underwent physical examinations, including assessment of tenderness on the AC joint and provocative tests (the Buchberger's test and the cross-body adduction stress test). Bilateral AC joints with the arm in both the resting and the cross-body positions were examined by ultrasound., Results: Twelve of 150 players (8 %) had AC symptoms with both positive tenderness and positive provocative tests. Interestingly, their prevalence increased with age-one of the 70 (1.4 %) 1st-3rd graders, six of 46 (13 %) 4th-6th graders and five of 34 (15 %) 7th-8th graders. Ultrasonography of AC joints in the cross-body position showed that the difference in superior capsular bulging between the throwing and non-throwing sides was significantly greater in symptomatic players (1.6 ± 1.2 mm) than in asymptomatic players (0.2 ± 0.8 mm) (p = 0.002)., Conclusion: The prevalence of superior capsular bulging was significantly higher in adolescent baseball players with AC joint pain than in those without it. In adolescent baseball players with shoulder pain, AC joint symptoms should be considered amongst potential causes. Careful observation of these patients is suggested in cases of superior capsular bulging of the AC joint as determined by ultrasonography., Level of Evidence: III.

The deadman theory is composed of two angles: θ1 and θ2, and it is recommended that both be less than or equal to 45°. Based on this theory, surgeons insert the anchor at 45°. However, the biomechanical studies show controversial data. We reviewed the original article and the biomechanical studies in the literature. We further performed three additional studies: 1) a finite element analysis to calculate the pullout strength of thread-less anchors inserted at 45°, 90°, and 135° to the polyurethane foam; 2) the same pullout test using thread-less anchors and the polyurethane foam; and 3) the same pullout test using metal threaded suture anchors and the simulated cortical bone. From the review and the additional studies, we came to the following explanations for the controversy: #1, the trigonometric calculation is not always applicable because of bone deformation; #2, insertion angle of 45° is the best for a thread-less anchor, but not for a threaded anchor; #3, θ1⩽45° is true, but it is not equivalent to inserting an anchor at 45°. In conclusion, insertion angle of 45° is the strongest for a thread-less anchor, but 90° is the strongest for a threaded anchor. The pullout strength depends on the inclination of the anchor, friction of the anchor-bone interface, and quality of the bone.

Background: The purpose of this brief report is to make clinical and research recommendations to advance current knowledge and practices related to the assessment of antipsychotic drug-induced movement disorders (DIMDs) via live interactive videoconferencing., Materials and Methods: The authors provide an overview of the frequent neurological side effects of antipsychotic drugs and review relevant telemedicine research. DIMD prevention is critical, but these disorders remain underdetected and under-reported. Although there are not yet formal recommendations for specific screening tools or screening frequency, baseline and annual assessments are generally agreed-upon minimums. As DIMD awareness increases and more specific guidelines are developed to steer assessments, telemental health may aid practitioners in efficiently and regularly monitoring onset and severity. Research shows that videoconferencing can be used for effective psychiatric treatments and assessment, with at least one study validating the use of videoconference assessment for a subset of movement disorders., Results and Conclusions: Clinical recommendations include developing practice-level protocols and procedures that include regular DIMD assessment (either in-person or via telemedicine) for the full spectrum of possible movement disorders for all patients taking antipsychotic medications. Research and evaluation recommendations include replicating and expanding upon the existing study using videoconferencing to assess movement disorder symptoms, using asynchronous telemental health assessments of DIMDs, and pilot-testing facial and movement recognition software to allow for clinical comparison of patients' movement patterns over time.

Objective: To examine the relationship between executive dysfunction, as a multidimensional construct (ie, decision-making, impulsivity, aggression, concept formation), and suicide attempt (SA) history in a high-risk sample of veterans with moderate to severe traumatic brain injury (TBI)., Design: Observational, 2×2 factorial design. To estimate group differences, linear regression was used to model the primary and secondary outcomes of interest as a function of history of SA, TBI, and the interaction between the 2 variables. Additionally, to determine the pattern of performance over the course of the Iowa Gambling Test (IGT), scores were modeled across the 5 IGT blocks by using a varying-coefficient model., Setting: Veterans Health Administration., Participants: Veterans (N=133; no SA/no TBI, n=48; no SA/yes TBI, n=51; yes SA/no TBI, n=12; yes SA/yes TBI, n=22) completed the study measures., Interventions: Not applicable., Main Outcome Measures: IGT, Immediate and Delayed Memory Test, State-Trait Anger Expression Inventory-2, Wisconsin Card Sorting Test., Results: All groups demonstrated learning over the course of the IGT, except for veterans with a history of both SA and TBI. No group differences were identified on other measures of executive functioning., Conclusions: These findings highlight the potential, unique decision-making challenges faced by veterans with a history of TBI and SA. Specialized interventions focused on overall distress reduction and means restriction may be required to prevent future self-directed violence., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Thickening of the medial ulnar collateral ligament in the throwing arm of adult baseball players is a well-known phenomenon. However, onset of the thickening is unclear among young baseball players. The purpose of this study was to evaluate the thickness of the medial ulnar collateral ligament in junior high and high school baseball players., Subjects and Methods: Seventy-one uninjured and asymptomatic junior high and high school baseball players were included in the study. Participants underwent physical examination after completing a questionnaire, followed by ultrasonographic evaluation. The thickness of the medial ulnar collateral ligament was measured bilaterally. The thickness of the throwing and non-throwing sides in high school and junior high school baseball players, and within each group, was compared and statistically analyzed., Results: The medial ulnar collateral ligament in the throwing arm of high school baseball players was thicker than that in the non-throwing arm (5.5 vs. 4.4 mm), although no significant difference was seen in junior high school baseball players. High school baseball players showed a significantly thicker medial ulnar collateral ligament in the throwing arm than junior high school baseball players., Conclusion: Thickening of the medial ulnar collateral ligament in the throwing arm of asymptomatic and uninjured baseball players may begin by the time the players reach high school.

Background: The muscle activity pattern during shoulder external rotation has not been fully clarified. This study aimed to determine the activities involved in external rotation in the adducted and abducted positions using positron emission tomography (PET)., Methods: Seven healthy volunteers underwent PET examinations after performing external rotation using an elastic band at both 0° and 90° of shoulder abduction in the frontal plane. External rotation exercise was performed before and after injection of fluorine 18 fluorodeoxyglucose, which was followed by PET examination. The protocols for external rotation exercise were identical between the 2 shoulder positions. To obtain control data, PET examination was also performed under resting conditions. The order of these 3 PET examinations was randomized, and they were performed at intervals of 1 week or greater. Each PET image was fused to the corresponding magnetic resonance image to identify each shoulder muscle. After this, the standardized uptake value was calculated in each muscle and was compared between the 2 shoulder positions., Results: The infraspinatus showed the greatest muscle activity during external rotation at 0° of abduction, whereas the teres minor showed the greatest activity at 90° of abduction. The teres minor-infraspinatus ratio at 90° of abduction (mean ± SD, 1.21 ± 0.23) was significantly higher than that at 0° of abduction (0.84 ± 0.15) (P < .01)., Conclusion: The infraspinatus and teres minor are the main shoulder external rotators. The teres minor is more important as an external rotator in abduction than in adduction., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: The purpose of this study was to investigate the incidence of venous thromboembolism (VTE) after elective arthroscopic shoulder surgery., Materials and Methods: One hundred seventy-five consecutive patients who underwent arthroscopic shoulder surgery were enrolled (mean age, 61 years). Patients who had VTE preoperatively and underwent trauma surgery or arthroplasty were excluded. All the patients used foot pumps or elastic stockings after surgery for deep venous thrombosis (DVT) prophylaxis. DVT in the 4 limbs was assessed by ultrasound before and after surgery. Pulmonary embolism was diagnosed by computed tomography pulmonary angiography. Risk factors related to DVT were assessed., Results: The overall incidence of DVT was 10 of 175 patients (5.7%). Most of the DVT cases were detected at 1 to 2 days after surgery. All patients were asymptomatic. There were no patients who had symptomatic pulmonary embolism. However, an asymptomatic pulmonary embolus developed in 1 patient during the 3-month follow-up period. There were no significant differences between the DVT and non-DVT groups regarding the risk factors., Discussion and Conclusion: Our data have shown that symptomatic VTE is rare after elective arthroscopic shoulder surgery. However, asymptomatic VTE may occur even with DVT preventive measures. Because most of the DVTs were found in the calf veins, we recommend that surgeons pay attention to the possibility of DVT in the lower extremities even after arthroscopic shoulder surgery. The incidence of asymptomatic VTE after elective arthroscopic shoulder surgery was 5.7%. All patients were asymptomatic, and most of the DVTs occurred 1 or 2 days after surgery., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: A large Hill-Sachs lesion has been considered a risk factor for postoperative recurrence of shoulder instability. However, there are few reports describing the prevalence of Hill-Sachs lesions that engage with the glenoid. The purpose of this study was to clarify the prevalence of engaging Hill-Sachs lesions using the concept of the glenoid track., Materials and Methods: The computed tomography images of 100 consecutive patients with unilateral recurrent anterior shoulder dislocations were assessed. An image in the plane perpendicular to the rotator cuff attachment was reconstructed from the DICOM (Digital Imaging and Communications in Medicine) data, and the maximum distance from the medial margin of the Hill-Sachs lesion to the medial margin of the rotator cuff footprint was measured. The location of the Hill-Sachs lesion in the glenoid track was assessed, and when the Hill-Sachs lesion extended medially over the glenoid track, it was defined as an "engaging Hill-Sachs lesion.", Results: Engaging Hill-Sachs lesions were observed in 7 of 100 cases (7%). There were 2 types of Hill-Sachs lesions: a large and wide type (3 cases) and a narrow but medially located type (4 cases). All cases with an engaging Hill-Sachs lesion had a large bony defect of the glenoid at the same time., Conclusions: In our series of consecutive 100 cases, the prevalence of engaging Hill-Sachs lesions was 7%. There were 2 types of Hill-Sachs lesions: a wide and large type and a narrow but medially located type., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Objective: The aim of this pilot study was to explore the relationship between executive dysfunction and suicidal behavior in two groups of participants: (Group 1, n = 18) veterans with traumatic brain injury (TBI) and a history of at least one suicide attempt (SA), and (Group 2, n = 29) veterans with TBI and no history of SA. Controlling for the severity of TBI, it was hypothesized that participants in Group 1 would perform more poorly than those in Group 2 on measures of executive functioning., Design: The primary outcome variable was decision making as assessed by performance on the Iowa Gambling Task (IGT). Secondary outcome variables included laboratory-measured impulsivity as measured by the Immediate and Delayed Memory Test (IMT/DMT), abstract reasoning as measured by the Wisconsin Card Sorting Test (WCST), and aggression as measured by the Lifetime History of Aggression (LHA) scale., Results: Among those in Group 1, time between TBI and first suicide attempt postinjury varied widely (months to nearly 30 years). Only the WCST perseverative errors score differed significantly between individuals with and without histories of one or more suicide attempts (SAs)., Conclusion: Suggestions for future study of SA among those with TBI are provided. When working with individuals with TBI, clinicians are encouraged to incorporate suicide risk assessment into their practice. Augmenting this process with a measure of perseveration may be beneficial., (PsycINFO Database Record (c) 2012 APA, all rights reserved.)

Rural American Indian veterans have unique healthcare needs and face numerous barriers to accessing healthcare services. Over the past decade, the Department of Veterans Affairs in conjunction with the University of Colorado Denver has turned to the promising field of telemental health to develop a series of videoconferencing-based clinics to reach this vulnerable population and improve mental healthcare services. The ongoing development, implementation, and expansion of these clinics have been assessed as part of a program improvement. The outcomes of these assessments have been documented in a series of published articles, controlled studies, program and case reports, and model descriptions. This article summarizes a decade of experience with the American Indian Telemental Health Clinics, the clinic model, and the literature arising from these clinics and presents lessons learned while establishing, maintaining, and evaluating these clinics. The ability to tailor the clinics to individual sites and cultures and to provide various services has been critical to the operation of the clinics. Culturally specific care through culturally knowledgeable providers, onsite tribal outreach workers, and collaboration with community services has proven essential in operating the clinics, as well as building rapport, trust, and engagement with the target patient population. It is hoped that the lessons learned and practices presented here can not only assist others working to improve the care for rural Native veterans but also serve as a model in the use of telemental health services for improving care and access to rural veteran and non-veteran populations.

Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

Background: Tetomilast (OPC-6535) was originally developed as a compound inhibiting superoxide production in neutrophils. Although its mechanism of action is not completely understood, phosphodiesterase type 4 inhibitory function has been postulated. The therapeutic effect of PDE4 inhibitors has been reported for chronic inflammatory disorders such as chronic obstructive pulmonary diseases. In this study we aimed to examine whether tetomilast could be a novel drug for inflammatory bowel diseases by further clarifying its antiinflammatory effects., Methods: Cytokines from human peripheral blood mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and Cytokine Beads Array. The transcripts were quantified by reverse-transcriptase polymerase chain reaction (RT-PCR). Phosphorylation of transcription factors was examined by phosflow. To examine its in vivo effect, a once-daily oral dose of tetomilast was tested in murine IL-10(-/-) chronic colitis., Results: Tetomilast suppressed TNF-alpha and IL-12 but not IL-10 production from lipopolysaccharide (LPS)-stimulated human monocytes. It suppressed TNF-alpha, IFN-gamma, and IL-10 from CD4 lymphocytes. Tetomilast suppressed cytokine production at the transcriptional level but did not alter phosphorylation of p65, ERK, p38, and STAT3. HT-89, a protein kinase A inhibitor, did not abolish the effect of tetomilast, suggesting that it was independent from the classical cAMP/PKA pathway. IL-10 was not essential to the inhibitory effect of tetomilast on TNF-alpha and IL-12. Tetomilast ameliorated IL-10(-/-) chronic colitis with reduced clinical symptoms, serum amyloid A, and histological scores with decreased TNF-alpha mRNA expression., Conclusions: Tetomilast exerts its antiinflammatory effects on human monocytes and CD4 cells. Combined with in vivo data these findings support the feasibility of tetomilast as a novel drug for inflammatory bowel diseases.

We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).

Background: The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat., Methods: P. acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments. In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL. The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide. Release of cytokines into the perfusate was examined. In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L., Results: In perfusion experiments, P. acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages. Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver. OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase., Conclusion: Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P. acnes- and lipopolysaccharide-treated rats.

Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms. Although often moderate to mild in severity, these symptoms are, nevertheless, associated with poorer over-all outcome. Recent studies suggest diminished nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit found in schizophrenia, failure of auditory sensory inhibition. Diminished inhibitory sensory gating also occurs in cocaine addicts, probably because of their increased catecholaminergic neurotransmission, which blocks the inhibition. In the present study, 11 cocaine addicts in the first week of detoxification were recorded electrophysiologically, after which the effects of 6 mg of nicotine gum, were assessed in a double-blind placebo-controlled crossover design. The test was repeated 10 days later. Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days. Although nicotine itself may not be a desirable therapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited therapeutic target for new drug development for the neuropsychiatric sequelae of cocaine addiction.

Many investigators have proposed that biological endophenotypes might facilitate the genetic analysis of schizophrenia. A deficit in the inhibition of the P50 evoked response to repeated auditory stimuli has been characterized as a neurobiological deficit in schizophrenia. This deficit is linked to a candidate gene locus, the locus of the alpha7-nicotinic cholinergic receptor subunit gene on chromosome 15q14. Supportive evidence has been found by other investigators, including: 1) linkage of schizophrenia to the same locus; 2) linkage of bipolar disorder to the locus; and 3) replication of the existence of this neurobiological deficit and its relation to broader neuropsychological deficits in schizophrenia. It is certain that there are many genetic factors in schizophrenia and bipolar disorder; what is needed is a complete and precise description of the contribution of each individual factor to the pathophysiology of these illnesses., (Copyright 2000 Wiley-Liss, Inc.)

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 +/- 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.

Previous studies have suggested that intracerebroventricular kainic acid injections alter brain anatomy and neurochemistry in a manner similar to what is observed in schizophrenic patients. Disturbances in sensory information processing are one of the major symptoms of schizophrenia. Thus, the present experiments were designed to evaluate the hypothesis that hippocampal damage, induced by administration of kainic acid, would alter the processing of auditory stimuli in a paired-click paradigm. Adult male Sprague-Dawley rats were implanted for surface recording of auditory evoked potentials. At the time of electrode implantation, the rats also received bilateral injections of either kainic acid or the vehicle solution. In vehicle-treated rats, the midlatency N40 component of the auditory evoked potential was diminished in amplitude by approximately 60% in response to the second of a pair of clicks delivered 0.5 s apart. By contrast, no reduction of the N40 wave evoked by the second click was observed in kainate-treated rats. Further, administration of haloperidol, a prototypical neuroleptic agent, did not improve this auditory processing dysfunction in kainate-treated animals. Loss of auditory filtering in the paired-click paradigm and a lack of response to haloperidol in this test are typically observed in schizophrenic humans. Thus, the present results demonstrate that kainate-lesioned rats possess a functional schizophrenia-like abnormality, further reinforcing the utility of this model system for studying the basic neurobiology of schizophrenia-induced sensory processing deficits.

A large body of evidence has demonstrated that inhibition of the neutrophil's oxidant burst attenuates sepsis-induced acute lung injury. The present study sought to evaluate the ability of OPC-6535, a superoxide anion production inhibitor, to attenuate sepsis-induced acute lung injury. Four groups of swine were anesthetized, ventilated, and studied for 5 hr. Following surgical preparation, control (n = 10) and OPC-control (n = 2) animals received a 1-hr infusion of sterile saline. Sepsis was induced with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. Untreated septic animals (n = 10) received no treatment. Animals treated with OPC-6535 (n = 6) received a 1 mg/kg bolus of OPC-6535 15 min prior to initiation of the bacterial infusion. Changes in systemic and pulmonary hemodynamics, arterial oxygen tension, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin expression, neutrophil oxidant burst, and lung myeloperoxidase content were used as outcome measures. Treatment with OPC-6535 significantly reduced acute lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. Treatment with OPC-6535 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with both treated and untreated sepsis exhibited significant up-regulation of CD18 and production of increased levels of oxidants, indicating significant activation when compared to neutrophils from control animals. Although animals treated with OPC-6535 produced 25% less superoxide anion than untreated septic animals, this decrease was not statistically significant. Treatment of animals with OPC-6535 prior to the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.

Background: Altered sensory response is a prominent feature of schizophrenia. Inhibitory gatting mechanisms, shown by diminished P50 evoked responses to repeated auditory stimuli, seem to be deficient in schizophrenic persons. These inhibitory mechanisms usually are studied by averaging the electroencephalographic responses to many presentations of pairs of stimuli. Although averaging increases signal-to-noise ratio, it may obscure trial-to-trial differences. We compared differences between schizophrenic and normal persons in single trials and averages of P50 response., Methods: Recordings from 10 schizophrenic patients and 10 normal subjects were analyzed using conventional averaging and single-trial measurements. A computer simulation of both methods examined their ability to extract evoked responses from background activity. Related single-neuron activity in the hippocampus in an animal model also was studied, because neuronal action potentials can be reliably identified in single trials., Results: Averaged evoked potentials showed significant suppression of the P50 response to the second stimulus of the pair in normal patients, but not in schizophrenic patients. Single-trial analysis did not detect a response above background activity. Computer simulations gave similar results, suggesting that failure to detect suppression in single trials comes from inadequate differentiation of signal from noise. Recordings in animals confirmed almost complete suppression of the response of hippocampal pyramidal neurons to the second stimulus., Conclusions: The normal inhibition of response to repeated auditory stimuli seems to be compromised in schizophrenia. This loss of inhibitory gating could reflect a physiological deficit of hippocampal interneurons that is consonant with other evidence for interneuron pathologic defects in schizophrenia.

Neutrophils have an important role in the self-defense systems of organisms through the production of superoxide. On the other hand, it has been proposed that abnormal amounts of superoxide produced by neutrophils are a serious factor in tissue injury. A series of novel thiazole derivatives was prepared and evaluated inhibitory effect on superoxide production by human neutrophils in vitro. Among these compounds, 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]-pyridine-2-carboxylic acid (OPC-6535) was selected as one of the most promising compounds. The synthesis and structure-activity relationships of these compounds are reported herein.

The evoked response to repeated auditory stimuli generally decreases in amplitude, a phenomenon that demonstrates the activity of sensory gating mechanisms in the central nervous system (CNS). Gating of the P50 wave of the auditory evoked response shows such behavior in normals, but not in schizophrenic or manic subjects. In mania, diminished gating of the auditory evoked response is correlated with elevated levels of noradrenergic metabolites. In animals, yohimbine, a presynaptic alpha-2 antagonist, increases noradrenergic neuronal transmission in the CNS and diminished gating of the auditory evoked response. The aim of this experiment was to test whether yohimbine causes diminished auditory sensory gating in normal human controls. Seven normal subjects with normal P50 auditory gating were treated either with 0.4 mg/kg of oral yohimbine on one day or placebo on a different day. Each subject acted as his own control. Yohimbine, but not placebo, caused a significant but transient decrease in P50 auditory gating in these subjects. Thus, increasing CNS noradrenergic neuronal transmission in normal controls can cause a transient impairment in auditory sensory gating.

Schizophrenia may result from the concerted action of several pathophysiological factors. This pilot study compared the distribution of measurements of three such putative factors in 11 schizophrenics and their siblings: a neurophysiological deficit in auditory sensory gating, diminished hippocampal volume, and increased catecholamine metabolism. Abnormal auditory sensory gating was found in all schizophrenics in the 11 families studied and in 8 of their 20 siblings. Compared with the schizophrenics, the clinically unaffected siblings with abnormal auditory gating had larger hippocampal volume. There was no similar difference for the siblings with normal gating. The siblings with abnormal auditory gating also had lower homovanillic acid levels than the other siblings. The data suggest that a familial neuronal deficit, identified by diminished sensory gating, may be a necessary, but not sufficient factor in the pathogenesis of schizophrenia. Individuals with this deficit are generally clinically unaffected, except for schizophrenics, who also have other abnormalities, such as diminished hippocampal volume and increased catecholamine metabolism.

The behavior of the P50 wave of the auditory evoked potential in a paired stimulus or conditioning-testing paradigm has been used as a measure of sensory gating disturbance in schizophrenia. Schizophrenics fail to decrement the P50 response to the second stimulus of the pair, so that the ratio of the test to the conditioning amplitude is elevated over normal values. The aim of this study was to compare this neurophysiological measure to neuropsychological measures of attention and memory. As expected, schizophrenics performed worse than controls on most measures. The time to complete a digit cancellation test, a measure of sustained attention, was found to be particularly longer in schizophrenics than in control subjects. Furthermore, the increased time to complete this task correlated with the increased ratio of the amplitude of the test P50 response to the conditioning response in the schizophrenics. Thus, a neurophysiological defect in sensory gating may relate to a disorder in sustained attention in schizophrenia. Although the P50 wave may come from the hippocampus, neuropsychological measures of verbal learning and memory were not correlated with alterations in the P50 ratio.

The effects of lithium carbonate were assessed in a double-blind, placebo-controlled study of a small group of recently detoxified alcoholics. The patients were treated during their 2nd and 3rd week of abstinence. A previous study demonstrated the existence in these patients of a syndrome of mildly elevated psychomotor rate, including irritability, grandiosity, an increased need for social contact, loquaciousness, and sexual preoccupation. The intensity of this syndrome was significantly decreased by treatment with low dose lithium carbonate, with no effect of placebo treatment.

Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.

This paper describes an elementary deficit in sensory processing in people with schizophrenia. If paired sounds are presented to normal subjects, the response to the first sound, as measured by the P50 wave of the auditory-evoked potential, is much greater than the response to the second sound. The diminished response to the second sound is an example of a sensory gating mechanism that enables people to regulate their vigilance so that they can either detect all sounds in the environment or ignore most of them, in favor of narrowing the focus of their concentration. In schizophrenia, this mechanism is usually deficient; patients are in a state of hypervigilance and have diminished abilities to focus their attention. The deficiency appears to be genetically determined and to involve the brainstem control of sensory input to the hippocampus. Such sensory gating deficits may underlie more complex psychotic symptoms, such as hallucinations and delusions. Further studies of their neurobiology could lead to increased understanding of the pathophysiology of schizophrenia.

Auditory evoked potentials were recorded using a paired stimulus, conditioning-testing paradigm from 14 schizophrenic patients and 13 normal subjects with no family history of psychotic disorder. Previous studies of the vertex P50 wave using this paradigm have demonstrated a possible sensory gating deficit in schizophrenics, as shown by their failure to diminish the response to a test stimulus presented 500 ms after a conditioning stimulus. Recordings were made at Cz, Fz, C3, T3, C4, and T4, to compare effects at different recording sites with this paradigm. Schizophrenics had significantly poorer sensory gating than normals, with the most significant difference between the groups at Cz. In addition to the 500 ms interval, subjects were also recorded at a conditioning-testing interval of 100 ms. Most schizophrenics showed normal sensory gating at the 100 ms interval, despite their abnormalities at 500 ms. The results indicate that Cz is optimal recording site for this paradigm, and that gating abnormalities in schizophrenic subjects are limited to specific interstimulus intervals.