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1.
JSES Int ; 7(5): 720-729, 2023 Sep.
Article En | MEDLINE | ID: mdl-37719811

Background: To investigate the characteristics of glenoid rim morphology in young athletes (<40 yr) with unstable painful shoulder. Methods: This was a retrospective case series. The inclusion criteria were as follows: (1) shoulder pain during sports activity, (2) traumatic onset, (3) no complaint of shoulder instability, and (4) soft tissue or bony lesions confirmed on imaging examinations (computed tomography and magnetic resonance imaging). The above-mentioned painful cohort was then compared (in a 2:1 ratio) to a match-paired control group of patients with similar demographics but with frank anterior glenohumeral instability as defined by imaging and physical findings. The pain (not apprehension) was reproduced during the anterior apprehension test in supine position and relieved by relocation test in all patients. Glenoid rim morphology, bone union in shoulders with a fragment-type glenoid, glenoid defect size, bone fragment size, medial displacement of bone fragments (MDBF), and medial distance of erosion (MDE) were compared between painful shoulders and unstable shoulders. Results: There were 79 painful shoulders and 165 unstable shoulders. The glenoid rim morphology was normal in 33 shoulders, erosion-type in 15 shoulders, and fragment-type in 31 shoulders among painful shoulders, whereas the respective shoulders were 19, 33, and 113 among unstable shoulders (P < .001). Bone union was complete in 15 shoulders, partial in 14 shoulders, and nonunion in 2 shoulders among painful shoulders, whereas the respective shoulders were 43, 31, and 39 among unstable shoulders (P = .001). The mean glenoid defect size was 6.0 ± 7.2% and 12.7 ± 7.4%, respectively (P < .001), and the mean bone fragment size was 5.8 ± 6.4% and 5.4 ± 4.6%, respectively, (P = .591). The mean MDBF was 1.4 ± 1.5 mm and 3.0 ± 2.2 mm, respectively (P < .001), and the mean MDE was 2.3 ± 1.2 mm and 5.2 ± 2.4 mm, respectively (P < .001). In shoulders with a smaller glenoid defect (<13.5%), the prevalence of shoulders with MDBF (<2 mm) and shoulders with MDE (<2 mm) was more frequent in painful shoulders. On the other hand, in shoulders with a larger glenoid defect (≥13.5%), erosion-type glenoid, nonunion in fragment-type glenoid and bone fragment smaller than 7.5% was not recognized in painful shoulders. Shoulders with MDBF (<2 mm) were significantly more frequent in painful shoulders (P = .009). Conclusions: In painful shoulders normal or erosion-type glenoid was predominant, and glenoid defect size was significantly smaller than unstable shoulders. On the other hand, a large bone fragment (≥7.5%) remained and united completely or partially in all shoulders with a larger glenoid defect (≥13.5%). Bone union was obtained within 2 mm from the articular surface in most of them.

2.
Bioengineering (Basel) ; 10(1)2023 Jan 11.
Article En | MEDLINE | ID: mdl-36671674

Mesenchymal stem cells (MSCs) hold considerable promise for regenerative medicine. Optimization of the seeding density of mononuclear cells (MNCs) improves the proliferative and differentiation potential of isolated MSCs. However, the underlying mechanism is unclear. We cultured human bone marrow MNCs at various seeding densities (4.0 × 104, 1.25 × 105, 2.5 × 105, 6.0 × 105, 1.25 × 106 cells/cm2) and examined MSC colony formation. At lower seeding densities (4.0 × 104, 1.25 × 105 cells/cm2), colonies varied in diameter and density, from dense to sparse. In these colonies, the proportion of highly proliferative MSCs increased over time. In contrast, lower proliferative MSCs enlarged more rapidly. Senescent cells were removed using a short detachment treatment. We found that these mechanisms increase the purity of highly proliferative MSCs. Thereafter, we compared MSCs isolated under optimized conditions with a higher density (1.25 × 106 cells/cm2). MSCs under optimized conditions exhibited significantly higher proliferative and differentiation potential into adipocytes and chondrocytes, except for osteocytes. We propose the following conditions to improve MSC quality: (1) optimizing MNC seeding density to form single-cell colonies; (2) adjusting incubation times to increase highly proliferative MSCs; and (3) establishing a detachment processing time that excludes senescent cells.

3.
PLoS One ; 18(1): e0280331, 2023.
Article En | MEDLINE | ID: mdl-36630412

Omidenepag isopropyl (OMDI) is an intraocular pressure (IOP)-lowering drug used to treat glaucoma. The active form of OMDI, omidenepag (OMD), lowers elevated IOP, the main risk factor for glaucoma, by increasing the aqueous humor outflow; however, a detailed understanding of this mechanism is lacking. To clarify the IOP-lowering mechanism of OMDI, the effects of OMD on the mRNA expression of the extracellular matrix, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were evaluated in human trabecular meshwork cells. Under 2D culture conditions, the mRNA expression of FN1, COL1A1, COL1A2, COL12A1, and COL13A1 decreased in a concentration-dependent manner after 6 or 24 h treatment with 10 nM, 100 nM, and 1 µM OMD, while that of COL18A1 decreased after 6 h treatment with 1 µM OMD. Significant changes in expression were observed for many MMP and TIMP genes. Under 3D culture conditions, the extracellular matrix-related genes COL12A1 and COL13A1 were downregulated by OMD treatment at all three concentrations. Under both 2D and 3D culture conditions, COL12A1 and COL13A1 were downregulated following OMD treatment. Reduction in the extracellular matrix contributes to the decrease in outflow resistance, suggesting that the downregulation of the two related genes may be one of the factors influencing the IOP-lowering effect of OMDI. Our findings provide insights for the use of OMDI in clinical practice.


Glaucoma , Trabecular Meshwork , Humans , Trabecular Meshwork/metabolism , Down-Regulation , Glaucoma/drug therapy , Glaucoma/genetics , Glaucoma/metabolism , Intraocular Pressure , Aqueous Humor/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Collagen Type XII/metabolism
4.
J Orthop Sci ; 27(4): 804-809, 2022 Jul.
Article En | MEDLINE | ID: mdl-34030939

BACKGROUND: A meniscal repair is often performed on radial/flap or longitudinal tears of the lateral meniscus (LM) combined with anterior cruciate ligament reconstruction (ACLR). However, it is unknown if meniscal extrusion changes over time after repair. This study evaluated whether meniscal extrusion of the LM is maintained after repair or progresses with time using magnetic resonance imaging (MRI). METHODS: Among 574 patients who underwent primary anatomic ACLR, 123 patients followed up for more than 2 years were retrospectively analyzed. Forty patients with concomitant radial/flap tears of the LM (group R), 43 with longitudinal LM tears (group L), and 40 with intact LM (group C, matched-control group) were included. Clinical findings (pain, range of motion, swelling, and anterior laxity), lateral joint space on radiograph, and meniscal extrusion on MRI were assessed. Lateral/posterior meniscal extrusions were examined preoperatively, within 3 weeks after surgery, and at the final follow-up, and the absolute values and relative values (the preoperative values as baseline) were assessed respectively. RESULTS: There were no significant differences in the clinical and roentgenographic findings among the groups. No difference was observed in the relative values within 3 weeks after surgery among three groups, although the absolute values were larger in the repaired groups than in group C. At the final follow-up, however, the lateral extrusion in group L had progressed significantly, compared with that in group C (P = 0.033), while no significant difference was detected in the lateral extrusion between groups R and C (P = 0.177). The posterior extrusion in groups R and L had progressed significantly compared with that in group C (P < 0.001). CONCLUSIONS: LM extrusion could not be improved even immediately after meniscal repair, and it progressed laterally and posteriorly for more than 2 years after surgery.


Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , Follow-Up Studies , Humans , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Retrospective Studies
5.
J Ocul Pharmacol Ther ; 37(4): 223-229, 2021 05.
Article En | MEDLINE | ID: mdl-33600237

Purpose: To investigate the intraocular pressure (IOP)-lowering effects of omidenepag isopropyl (OMDI), a potent and highly selective prostanoid EP2 receptor agonist, as a potential first-line ocular hypotensive agent when combined with existing antiglaucoma agents in conscious ocular normotensive monkeys. Methods: Male cynomolgus monkeys were examined under conscious conditions. OMDI ophthalmic solution alone was topically applied to an eye or combined with other ophthalmic solutions at 5-min intervals. The contralateral eye was left untreated. IOP was measured before and at 2, 4, 6, and 8 h after instillation. Results: Topical application of OMDI to the eye resulted in statistically significant IOP reduction, which lasted for at least 6 h. The IOP-lowering effects of OMDI concomitantly administered with any of the tested antiglaucoma agents (timolol, brinzolamide, netarsudil, ripasudil, and brimonidine) were greater than those of OMDI alone. Furthermore, these enhanced IOP responses to their concomitant use were statistically significant compared with those of the tested antiglaucoma agents alone. Any combination of OMDI with the tested agents did not lead to serious abnormalities either systemically or locally in the eye. Conclusions: We demonstrated that OMDI has additive IOP-lowering effects when administered in combination with various antiglaucoma agents, namely, ß-adrenergic antagonist, carbonic anhydrase inhibitor, Rho-associated coiled-coil containing protein kinase inhibitors, and α2-adrenergic agonist. These results suggest that OMDI provides additional clinical benefits because of its unique mechanisms of action when combination therapy is required.


Glaucoma/drug therapy , Glycine/analogs & derivatives , Intraocular Pressure/drug effects , Pyrazoles/pharmacology , Pyridines/pharmacology , Receptors, Prostaglandin E, EP2 Subtype/agonists , rho-Associated Kinases/antagonists & inhibitors , Administration, Topical , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic beta-Antagonists/administration & dosage , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Carbonic Anhydrase Inhibitors/administration & dosage , Case-Control Studies , Consciousness , Drug Synergism , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/statistics & numerical data , Glycine/administration & dosage , Glycine/pharmacology , Macaca fascicularis , Male , Ophthalmic Solutions/administration & dosage , Pyrazoles/administration & dosage , Pyridines/administration & dosage , Tonometry, Ocular/methods , rho-Associated Kinases/metabolism
6.
Am J Sports Med ; 49(3): 684-692, 2021 03.
Article En | MEDLINE | ID: mdl-33449798

BACKGROUND: Meniscal function after repair of longitudinal tears of the lateral meniscus (LM) with anterior cruciate ligament reconstruction (ACLR) has not been comprehensively investigated. PURPOSE: To evaluate not only the clinical outcomes and radiographic findings of patients who underwent repair of longitudinal tears of the LM combined with ACLR but also the healing status of the repaired meniscus and changes in chondral status with second-look arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Among 548 patients who underwent primary anatomic ACLR at our institution between 2010 and 2017, 39 who had concomitant longitudinal tears of the LM and underwent repair were studied. During follow-up for more than 2 years, all patients were evaluated clinically (pain, range of motion, swelling, and knee instability) and with imaging (plain radiograph and magnetic resonance imaging [MRI]), and compared with a matched control group (based on age, sex, body mass index, and follow-up period) without any concomitant injuries who underwent ACLR. Measurements on MRI were recorded preoperatively, immediately after surgery, and at final follow-up, and the change in the values over time was assessed. Of the 39 patients in each group, 24 were assessed by second-look arthroscopy with hardware removal 2 years postoperatively. RESULTS: The mean follow-up times of the study and control group were at a mean of 42.4 and 45.4 months, respectively. There were no significant differences in clinical findings, lateral joint space narrowing on radiographs, and chondral status at the lateral compartment between groups, whereas lateral and posterior meniscal extrusion on MRI progressed significantly in the study group (0.43 ± 1.0 mm vs -0.29 ± 1.1 mm, P = .003; 1.9 ± 1.9 mm vs 0.14 ± 1.1 mm, P < .0001, respectively). Second-look arthroscopy revealed complete healing in 12 patients (50%), partial healing in 9 (37.5%), and failure in 3 (12.5%) in the study group, and no new tear in the control group. CONCLUSION: The clinical and imaging outcomes after repair of longitudinal tears of the LM combined with anatomic ACLR were successful and comparable with those after isolated ACLR without any other injuries at 42 months postoperatively, although meniscal extrusion showed progression on coronal/sagittal MRI. Based on the MRI findings and the result that only half of patients achieved complete healing, meniscal function could not be fully restored even after repair. Although degenerative changes were not apparent, longer-term follow-up is needed.


Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Tibial Meniscus Injuries , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/surgery , Arthroscopy , Humans , Menisci, Tibial/surgery , Retrospective Studies , Second-Look Surgery , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery
7.
J Ocul Pharmacol Ther ; 36(7): 529-533, 2020 09.
Article En | MEDLINE | ID: mdl-32412835

Purpose: The present study investigated the effects of the antiglaucoma agent and selective E2 receptor agonist omidenepag isopropyl (OMDI) on eyelash growth in comparison with a prostaglandin analog (prostamide receptor agonist) in mice. Methods: Four-week-old female mice (C57BL/6J) were divided into 3 groups of n = 10 each. The groups were administered 3 µL of 0.003% OMDI solution, the vehicle (negative control), or a 0.03% bimatoprost solution (positive control) on the upper eyelids of the right eyes once daily for 14 days. On the 15th day, all animals were euthanized, and the upper eyelids with eyelashes were fixed with 10% neutral formalin. Eyelashes were evaluated for number, length, and thickness using a stereomicroscope. Specimens were then paraffin-embedded and stained with hematoxylin and eosin, followed by microscopic examination to assess eyelash morphology and growth cycle. Results: Eyelash number (143.5 ± 6.7/eyelid), thickness, and percentage of dermal papilla in the anagen phase in the OMDI group were similar to those observed in the vehicle group (eyelash number, 144.2 ± 5.7/eyelid). In contrast, eyelash number (166.7 ± 7.0/eyelid), thickness, and the percentage of dermal papilla in the anagen phase were significantly greater in the bimatoprost group compared with those of the vehicle group. Conclusions: Unlike existing prostaglandin analogs, our findings indicate that OMDI has no effect on eyelash growth in mice, suggesting that it may be a promising antiglaucoma agent with a reduced number of adverse effects.


Bimatoprost/toxicity , Eyelashes/drug effects , Glycine/analogs & derivatives , Pyrazoles/toxicity , Pyridines/toxicity , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/toxicity , Bimatoprost/administration & dosage , Eyelashes/growth & development , Female , Glycine/administration & dosage , Glycine/toxicity , Mice , Mice, Inbred C57BL , Microscopy , Pyrazoles/administration & dosage , Pyridines/administration & dosage , Receptors, Prostaglandin E, EP2 Subtype/agonists
8.
J Orthop Sci ; 25(6): 1061-1066, 2020 Nov.
Article En | MEDLINE | ID: mdl-32063466

BACKGROUND: Graft fixation at quantitative tension using a manual tensioner was advocated in ACL reconstruction, while the measured tension that is based on the surgeon's hand with the tensioner decreases after graft fixation. Therefore, our purpose is to elucidate how effectively the pre-determined graft tension maintained after final fixation of the graft to the tibia using a tensioning boot system fixed to the calf with a bandage, while monitoring the graft tension based on tibia. METHODS: Eight cadaveric legs (mean age: 83; 3 males and 5 females) underwent an anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with hamstring tendon grafts. Two tension-adjustable force gauges were installed on the lateral femoral cortex beside the femoral tunnel. Then #5 strong suture wires through the loop end of grafts were tied to the force gauges using Endo-Buttons. After manual maximum load was repeatedly applied to each graft for 3 min, the grafts were fixed to the tibia with 10 N or 20 N at 20 degree of flexion with the following tensioning techniques using double spike plate system: (1) Manually tensioning technique (MT); (2) Tensioning boot technique with flexion-extension motion (TB-FE); and (3) Tensioning boot technique with repetitive pull (TB-RP). The residual tension at 20 was measured 3 min after grafts fixation, and also after 10 and 50 times of repeated flexion-extension motion. One-way repeated measures ANOVA was used for statistical analysis among the three techniques. RESULTS: There were significant differences among three techniques fixing grafts with 10/20 N of initial tension in the residual tension 3 min after graft fixation and after 10 and 50 times of repeated flexion-extension motion. Among them, the residual tension in TB-RP was the greatest in most conditions. CONCLUSION: TB-RP is the most secure procedure to maintain the graft tension closer to the intended initial tension in ACL reconstruction.


Anterior Cruciate Ligament Reconstruction , Anterior Cruciate Ligament , Aged, 80 and over , Anterior Cruciate Ligament/surgery , Biomechanical Phenomena , Cadaver , Female , Humans , Knee Joint/surgery , Male , Tibia/surgery
9.
J Ocul Pharmacol Ther ; 36(3): 162-169, 2020 04.
Article En | MEDLINE | ID: mdl-31934812

Purpose: We aimed at comparing the effects of omidenepag (OMD) with those of prostaglandin F (FP) receptor agonists (FP agonists) on adipogenesis in mouse 3T3-L1 cells. Methods: To evaluate the agonistic activities of OMD against the mouse EP2 (mEP2) receptor, we determined cAMP contents in mEP2 receptor-expressing CHO cells by using radioimmunoassays. Overall, 3T3-L1 cells were cultured in differentiation medium for 10 days and adipocyte differentiation was assessed according to Oil Red O-stained cell areas. Changes in expression levels of the adipogenic transcription factors Pparg, Cebpa, and Cebpb were determined by using real-time polymerase chain reaction (PCR). OMD at 0.1, 1, 10, and 40 µmol/L, latanoprost free acid (LAT-A) at 0.1 µmol/L, or prostaglandin F2α (PGF2α), at 0.1 µmol/L were added to cell culture media during adipogenesis. Oil Red O-stained areas and expression patterns of transcription factor targets of OMD or FP agonists were compared with those of untreated controls. Results: The 50% effective concentration (EC50) of OMD against the mEP2 receptor was 3.9 nmol/L. Accumulations of Oil Red O-stained lipid droplets were observed inside control cells on day 10. LAT-A and PGF2α significantly inhibited the accumulation of lipid droplets; however, OMD had no effect on this process even at concentrations up to 40 µmol/L. LAT-A and PGF2α significantly suppressed Pparg, Cebpa, and Cebpb gene expression levels during adipocyte differentiation. Conversely, OMD had no obvious effects on the expression levels of these genes. Conclusions: A selective EP2 receptor agonist, OMD, did not affect the adipocyte differentiation in 3T3-L1 cells, whereas FP agonists significantly inhibited this process.


3T3-L1 Cells/drug effects , Adipocytes/drug effects , Adipogenesis/drug effects , Glycine/analogs & derivatives , Latanoprost/pharmacology , Pyrazoles/pharmacology , Pyridines/pharmacology , Receptors, Prostaglandin E, EP2 Subtype/agonists , 3T3-L1 Cells/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Animals , CHO Cells/drug effects , CHO Cells/metabolism , Cell Differentiation/drug effects , Cricetulus , Cyclic AMP/metabolism , Disease Models, Animal , Glycine/pharmacology , Lipid Droplets/drug effects , Lipid Droplets/metabolism , Mice , Prostaglandins F, Synthetic/pharmacology , Radioimmunoassay/methods
10.
Am J Sports Med ; 47(12): 2888-2894, 2019 10.
Article En | MEDLINE | ID: mdl-31469576

BACKGROUND: Meniscal function after repair of radial/flap tears of the posterior horn of the lateral meniscus (LM) with anterior cruciate ligament reconstruction (ACLR) has not been comprehensively investigated. PURPOSE: To evaluate not only the clinical and radiographic outcomes of patients with repair of radial/flap tears of the posterior LM with ACLR but also the healing status of the repaired meniscus and changes of chondral status with second-look arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From January 2008 to April 2016, 41 patients of a consecutive series of 505 primary anatomic ACLR cases had a concomitant radial/flap tear of the posterior horn of the LM and underwent side-to-side repair with an inside-out or all-inside technique. All patients were followed for >2 years, evaluated clinically and radiologically (radiograph and magnetic resonance imaging [MRI]), and compared with a control group without any concomitant injuries that underwent ACLR. Of the 41 patients, 30 were assessed by second-look arthroscopy 2 years postoperatively. RESULTS: The mean follow-up times of the study and control groups were 3.4 and 3.9 years, respectively. The study group showed no significant differences in clinical findings, lateral joint space narrowing on radiograph, and coronal extrusion on MRI as compared with the control group, whereas sagittal extrusion on MRI progressed significantly in the study group (1.2 ± 1.5 mm vs 0.32 ± 1.0 mm, P < .001). Eighteen patients (60%) obtained complete healing; 9 (30%) showed partial healing; and 3 (10%) failed to heal on second-look arthroscopy. Changes of chondral status in the femoral condyle showed no significant difference between the groups (P = .29). However, chondral status of the lateral tibial plateau worsened significantly in the study group (P = .0011). CONCLUSION: The clinical and radiographic outcomes after repair of radial/flap tears of the posterior horn of the LM as combined with anatomic ACLR were successful and comparable with those after isolated ACLR without any other injuries at a mean postoperative follow-up of 3.4 years, except for sagittal extrusion on MRI. Chondral lesions of the lateral tibial plateau deteriorated regardless of meniscal healing at 2 years postoperatively. Surgeons should keep in mind that chondral injuries might progress over the midterm.


Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction , Tibial Meniscus Injuries/surgery , Adolescent , Adult , Anterior Cruciate Ligament Injuries/diagnostic imaging , Arthroscopy , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Menisci, Tibial/surgery , Middle Aged , Radiography , Second-Look Surgery , Tibial Meniscus Injuries/diagnostic imaging , Treatment Outcome , Wound Healing , Young Adult
11.
Nihon Shokakibyo Gakkai Zasshi ; 116(3): 256-264, 2019.
Article Ja | MEDLINE | ID: mdl-30853679

We herein report a rare case of autoimmune pancreatitis with small intestinal obstruction. A 72-year-old male was admitted to our hospital with abdominal fullness and vomiting and diagnosed with autoimmune pancreatitis by imaging and laboratory tests. Imaging studies also revealed narrowing of the proximal jejunum with dilated bowels and intramural cystic lesion adjacent to the pancreatic body. Small bowel resection was performed to alleviate stenosis. Pathological evaluation demonstrated invasion of IgG4-positive cells and fibrosis.


Autoimmune Diseases/diagnosis , Constriction, Pathologic/diagnosis , Intestinal Obstruction/diagnosis , Pancreatitis/diagnosis , Aged , Humans , Male , Pancreas , Pancreatitis/immunology
12.
Nihon Hinyokika Gakkai Zasshi ; 110(1): 47-51, 2019.
Article Ja | MEDLINE | ID: mdl-31956219

We report two cases of pediatric deep renal injury at a local hospital. Case 1 was a 13-year-old girl. She fell from a bicycle and hit her back in a gutter. She complained of left back pain. Computed tomography (CT) revealed left deep renal injury accompanied by peripancreatic hematoma. Emergent surgery was performed and the transected kidney was resected, but pancreatic injury was not noted. Case 2 was a 10-year-old girl. She slipped during walking on her way home from school and hit her back on a concrete block. She complained of left back pain and gross hematuria. CT revealed left deep renal injury. Interventional radiology (IVR) was performed, but arterial bleeding was not noted, and so conservative therapy was performed. Although pediatric deep renal injury might be treated conservatively in general, treatment of such cases should be performed ideally at a hospital with IVR available for general anesthesia, and radiologists on-call in the event of any sudden change in the patient's condition. However, pediatric patients with serious renal injury, including the above, who cannot be transported to an advanced treatment hospital, can be treated through cooperation between skilled interventional radiologists and surgeons even in local hospitals with limited facilities and manpower.


Kidney/injuries , Adolescent , Child , Female , Hospitals , Humans , Kidney/diagnostic imaging , Medically Underserved Area , Radiology, Interventional , Tomography, X-Ray Computed , Trauma Severity Indices
13.
J Ocul Pharmacol Ther ; 34(7): 531-537, 2018 09.
Article En | MEDLINE | ID: mdl-29989843

PURPOSE: To investigate the mechanism of the intraocular pressure (IOP)-lowering effect of a novel selective prostaglandin E2 receptor 2 (EP2) receptor agonist, omidenepag isopropyl (OMDI). METHODS: The effect of OMDI on IOP and aqueous humor dynamics was evaluated in cynomolgus monkeys with unilateral laser-induced ocular hypertension. In a crossover manner, the hypertensive eye of each monkey was dosed once daily with 20 µL of either 0.002% OMDI or vehicle. On day 7 of dosing, IOP was measured by pneumatonometry, aqueous humor flow and outflow facility were evaluated by fluorophotometry, and uveoscleral outflow was calculated mathematically. Treatments were compared by paired t-tests. RESULTS: OMDI at 0.002% significantly lowered IOP by 27%, 35%, and 44% at 0.5, 1.5, and 4 h after the last dosing, respectively. There was no difference in aqueous humor flow between vehicle and OMDI treatments. When comparing OMDI to the vehicle treatment, outflow facility and uveoscleral outflow were significantly (P < 0.05) increased by 71% and 176%, respectively. CONCLUSIONS: OMDI, a novel IOP-lowering compound, reduced IOP by increasing outflow facility and uveoscleral outflow in nonhuman primates.


Aqueous Humor/drug effects , Glycine/analogs & derivatives , Intraocular Pressure/drug effects , Ocular Hypertension/drug therapy , Ophthalmic Solutions/pharmacology , Pyrazoles/pharmacology , Pyridines/pharmacology , Receptors, Prostaglandin E, EP2 Subtype/agonists , Administration, Topical , Animals , Aqueous Humor/metabolism , Dose-Response Relationship, Drug , Female , Glycine/administration & dosage , Glycine/chemistry , Glycine/pharmacology , Humans , Lasers , Macaca fascicularis , Molecular Structure , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/chemistry , Pyrazoles/administration & dosage , Pyrazoles/chemistry , Pyridines/administration & dosage , Pyridines/chemistry
14.
J Med Chem ; 61(15): 6869-6891, 2018 08 09.
Article En | MEDLINE | ID: mdl-29995405

EP2 receptor agonists are expected to be effective ocular hypotensive agents; however, it has been suggested that agonism to other EP receptor subtypes may lead to undesirable effects. Through medicinal chemistry efforts, we identified a scaffold bearing a (pyridin-2-ylamino)acetic acid moiety as a promising EP2-selective receptor agonist. (6-((4-(Pyrazol-1-yl)benzyl)(pyridin-3-ylsulfonyl)aminomethyl)pyridin-2-ylamino)acetic acid 13ax (omidenepag, OMD) exerted potent and selective activity toward the human EP2 receptor (h-EP2). Low doses of omidenepag isopropyl (OMDI), a prodrug of 13ax, lowered intraocular pressure (IOP) in ocular normotensive monkeys. OMDI was selected as a clinical candidate for the treatment of glaucoma.


Acetates/metabolism , Acetates/pharmacology , Glaucoma/drug therapy , Prodrugs/metabolism , Pyridines/metabolism , Pyridines/pharmacology , Receptors, Prostaglandin E, EP2 Subtype/agonists , Acetates/chemistry , Acetates/therapeutic use , Animals , Drug Discovery , Macaca fascicularis , Pyridines/chemistry , Pyridines/therapeutic use , Structure-Activity Relationship
15.
Invest Ophthalmol Vis Sci ; 59(1): 145-153, 2018 01 01.
Article En | MEDLINE | ID: mdl-29332128

Purpose: The objective of this study was to investigate the pharmacologic characteristics of omidenepag isopropyl (OMDI), a compound developed as a novel intraocular pressure (IOP)-lowering agent, with better IOP control and fewer side effects than other prostanoid receptor agonists such as prostaglandin F receptor (FP) agonists. Methods: Binding activities of OMDI and its hydrolyzed form, omidenepag (OMD), to human recombinant prostanoid receptors (DP1-2, EP1-4, FP, and IP) were evaluated. Based on these binding assays, the agonistic activities of OMDI and OMD were further evaluated using cultured cells expressing selected prostanoid receptors. The pharmacokinetics of OMDI after topical administration was assessed in rabbits by measurement of the concentrations of both OMDI and OMD in aqueous humor. The ocular hypotensive effect of OMDI was evaluated in ocular normotensive rabbits, dogs, and both ocular normotensive and hypertensive monkeys. Results: OMD was determined to be a selective EP2 receptor agonist. OMDI weakly bound to EP1; however, the agonistic activity of OMDI to this receptor was not demonstrated in the functional assay. After topical administration of OMDI, OMD was detected in aqueous humor whereas OMDI was not detectable. OMDI significantly lowered IOP in both ocular normotensive and hypertensive animals. The significant ocular hypotensive effects of OMDI were demonstrated by both single and repeated dosing, and its effective duration suggests sufficient efficacy by once-daily dosing. Conclusions: These studies demonstrated that OMDI is hydrolyzed in the eye to OMD, an EP2 receptor agonist, with a significant ocular hypotensive effect in both ocular normotensive and hypertensive animal models.


Antihypertensive Agents/pharmacokinetics , Aqueous Humor/metabolism , Glaucoma/drug therapy , Intraocular Pressure/drug effects , Receptors, Prostaglandin E, EP2 Subtype/agonists , Administration, Topical , Animals , Antihypertensive Agents/administration & dosage , Disease Models, Animal , Glaucoma/metabolism , Macaca fascicularis , Rabbits
16.
Am J Sports Med ; 45(9): 1967-1974, 2017 Jul.
Article En | MEDLINE | ID: mdl-28426240

BACKGROUND: The usefulness of arthroscopic Bankart repair for collision/contact athletes has varied in previous reports. PURPOSE: To investigate the influence of glenoid rim morphologic characteristics on the clinical outcome after arthroscopic Bankart repair without additional reinforcement procedures in male collision/contact athletes, including athletes with a large glenoid defect. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Eighty-six athletes (93 shoulders) followed for a minimum of 2 years were retrospectively investigated. The sports were rugby (36 shoulders), American football (29 shoulders), and other collision/contact sports (28 shoulders). Preoperative glenoid defect size, bone fragment size, and bone union after bony Bankart repair were investigated regarding factors influencing postoperative recurrence. Postoperative changes in glenoid defect size and bone fragment size were investigated as well as their influence on the clinical outcome. RESULTS: Postoperative recurrence of instability was noted in 22 shoulders (23.7%). The recurrence rate was 33.3% in rugby, 17.2% in American football, and 17.9% in other collision/contact sports. The recurrence rate was only 7.1% in 28 shoulders without a preoperative glenoid defect, but it increased to 43.8% in 16 shoulders that did not have a bone fragment even though there was a preoperative glenoid defect. Additionally, the recurrence rate was 7.7% in 26 shoulders with bone union after arthroscopic bony Bankart repair but rose to 45% in 20 shoulders without bone union. In the shoulders with bone union, the mean bone fragment size increased from 8.2% preoperatively to 15.2% postoperatively, while the mean glenoid defect size decreased from 18.0% to 2.8%, respectively. The recurrence rate was 8.3% in shoulders with a final glenoid defect 5% or less versus 38.1% in shoulders with a defect greater than 5%. While the recurrence rate was low among athletes other than rugby players with a final defect of 10% or less, it was low in only the rugby players with a defect of 0%. CONCLUSION: In male collision/contact athletes, while the overall clinical outcome was unsatisfactory, a favorable outcome was achieved in athletes without a preoperative glenoid defect and athletes with bone union. The glenoid defect decreased in size postoperatively due to remodeling of the united bone fragment, and the recurrence rate was low when the final glenoid defect size was 5% or less.


Arthroscopy/statistics & numerical data , Athletic Injuries/surgery , Bankart Lesions/surgery , Shoulder Joint/surgery , Adult , Arthroplasty/methods , Arthroscopy/methods , Athletes , Athletic Injuries/pathology , Bankart Lesions/pathology , Case-Control Studies , Football/injuries , Fractures, Bone/surgery , Humans , Joint Instability/surgery , Male , Recurrence , Retrospective Studies , Scapula/surgery , Shoulder Joint/pathology , Treatment Outcome , Young Adult
17.
Knee Surg Sports Traumatol Arthrosc ; 25(4): 1219-1226, 2017 Apr.
Article En | MEDLINE | ID: mdl-26585909

PURPOSE: The purpose was to evaluate the cross-sectional area changes in hamstring tendon autografts up to 5 years after the anatomic triple-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 178 MRI scans from 139 patients (35 males, 104 females, mean age 30.4 years) with the anatomic triple-bundle ACL reconstructions were obtained to evaluate the cross-sectional area of the ACL grafts. They were classified into seven groups according to the period from reconstruction to MRI evaluation: Group -2 months (m.), Group 3-6 m., Group 7-12 m, Group 1-2 years (y.), Group 2-3 y., Group 3-4 y., and Group 4 y.-. Intra-operatively, the cross-sectional area of the graft was measured directly using a custom-made area micrometre. Post-operatively, the cross-sectional area of the grafts' mid-substance was measured with oblique axial MRI slices perpendicular to the long axis of the grafts using a digital radiology viewing program. The percent increase in the cross-sectional area was calculated by dividing the post-operative cross-sectional area by the intra-operative cross-sectional area. RESULTS: The mean percent increase in the cross-sectional area in Groups -2 m., 3-6 m., 7-12 m., 1-2 y., 2-3 y., 3-4 y., and 4 y.- was 105.7 ± 14.0, 134.9 ± 20.0, 137.3 ± 27.8, 129.4 ± 22.2, 124.1 ± 20.4, 117.8 ± 16.9, and 117.1 ± 17.2 %, respectively. The percent increase in Groups 3-6 m., 7-12 m., and 1-2 y. was significantly greater than in Group -2 m., while that in Group 4 y.- was significantly less than in Group 7-12 m. CONCLUSIONS: The cross-sectional area of the hamstring tendon autografts after the anatomic triple-bundle ACL reconstruction increases over time up to 1 year post-operatively, decreases gradually thereafter, and reaches plateau at around 3 years. LEVEL OF EVIDENCE: Retrospective case series, Level IV.


Anterior Cruciate Ligament Reconstruction/methods , Autografts/anatomy & histology , Hamstring Tendons/transplantation , Adult , Anterior Cruciate Ligament/surgery , Autografts/diagnostic imaging , Female , Hamstring Tendons/anatomy & histology , Hamstring Tendons/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Postoperative Period , Retrospective Studies , Transplantation, Autologous
18.
Nihon Jibiinkoka Gakkai Kaiho ; 119(6): 867-73, 2016 06.
Article Ja | MEDLINE | ID: mdl-30010287

Though tonsillectomy is one of the most common surgical procedures in otorhinolaryngology generally for benign diseases and mainly for young people, uncontrollable perioperative bleeding associated with tonsillectomy is a rare but potentially life-threatening event. We report herein on a case of a 19-year-old female with uncontrollable hemorrhage during a tonsillectomy, which was controlled through selective embolization. To the best of our knowledge, this is the first report on endovascular treatment in the management of tonsillectomy-associated intraoperative uncontrollable hemorrhage rather than postoperative bleeding. Selective embolization for perioperative bleeding during a tonsillectomy is considered as an efficient and important therapeutic option in the definitive treatment of this life-threatening occurrence. We also reviewed patients who underwent tonsillectomy in our hospital in the past five years. The ratio of postoperative hemorrhage was 11.8%. All patients with post-tonsillectomy hemorrhage were classified as grade 1 bleeding (spontaneous cessation).


Embolization, Therapeutic , Hemorrhage/therapy , Intraoperative Complications/therapy , Tonsillectomy/adverse effects , Female , Humans , Intraoperative Complications/diagnostic imaging , Tomography, X-Ray Computed , Tonsillitis , Young Adult
19.
Nihon Hinyokika Gakkai Zasshi ; 107(3): 198-202, 2016.
Article Ja | MEDLINE | ID: mdl-28740053

We report a 25-year-old male with multiple visceral injuries accompanied by right renal pedicle injury and left ureteral disruption treated successfully by left ureterocalicostomy. He was accidentally crushed by a roller for fishing net hoists while working as a fisherman in May 2011. He was emergently transported to Kurobe City Hospital. He was in shock, but recovered with fluid therapy. CT revealed bilateral hemothorax, liver injury, bowel injury, right renal pedicle injury, left renal injury, and inferior vena cava damage. After bilateral chest drainage, emergent surgery was performed. Laparotomy revealed pancreatic injury, liver injury, disruption of the stomach and jejunum, colonic injury, and retroperitoneal hematoma on the right side. Distal pancreatectomy, hepatorrhaphy, left half resection of the colon, subtotal gastrectomy, and colostomy were performed. However, the bleeding of the right lobe of the liver could not be stopped, and gauze packing on the liver surface was performed for damage control. During the operation, right renal pedicle injury was not treated because the pulsation of the retroperitoneal hematoma was not palpable and the hematoma did not enlarge to the left side across the center; furthermore, his general condition was very poor. After the operation, the patient showed anuria, and hemodialysis was performed twice a week. One week after the operation, removal of the gauze was performed under general anesthesia. The gauze was removed from the liver while sprinkling physiological saline, and there was little bleeding. Tachocomb® (CSL Behring, Tokyo, Japan) was placed on the surface of the liver and a drainage tube was indwelled. Twenty-four days postoperatively, CT revealed left hydronephrosis with right nonfunctioning kidney, and percutaneus left nephrostomy was performed. Antegrade and retrograde pyelograms revealed a left ureteral defect of 8 cm in the upper ureter.The patient was introduced to the Department of Urology of Shinshu University Hospital. Left ureterocalicostomy was performed in January 2012, and the nephrostomy catheter was removed. The temporal colostomy was closed in the Department of Surgery of Kurobe City Hospital in May 2014. He subsequently resumed his normal life.

20.
J Foot Ankle Surg ; 53(2): 194-8, 2014.
Article En | MEDLINE | ID: mdl-24556487

Insertional Achilles tendon injuries can be difficult to treat when minimal tendon tissue remains for anastomosis. Moreover, in the chronic case with tendon shortening, operative repair can be more difficult than acute rupture. It is particularly desirable to reinforce the tendons, in addition to performing primary repair, in patients with renal or systemic diseases because of the accelerated collagen degeneration. Many techniques have been described for the surgical management of Achilles tendon rupture; however, none has shown clear superiority. We report the case of a 50-year-old renal transplant patient with a spontaneous distal Achilles tendon injury that we repaired using the pull-out technique reinforced with an autologous semitendinosus graft. At 2 years postoperatively, the ankle-hindfoot scale score was 92 points, and the postoperative course was without complication. We believe that the free hamstring tendon autograft is advantageous for this repair, because it is easy to handle, has limited donor site morbidity, and preserves the structures around the ankle.


Achilles Tendon/surgery , Kidney Transplantation , Tendon Injuries/surgery , Tendons/transplantation , Achilles Tendon/injuries , Calcaneus/injuries , Fractures, Bone/surgery , Humans , Kidney Failure, Chronic/surgery , Male , Middle Aged , Rupture , Transplantation, Autologous
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