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1.
Geriatr Orthop Surg Rehabil ; 14: 21514593231195539, 2023.
Article in English | MEDLINE | ID: mdl-37600451

ABSTRACT

Introduction: The purpose of this study was to identify the timing and nature of complications associated with distal femur fracture surgery in patients aged 65 and older using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Methods: The ACS NSQIP database was queried for adults aged 65 and older who received surgical treatment for a distal femur fracture between 01 January 2015 and 31 December 2021. Cox regression models and risk tables adjusted for baseline clinical characteristics were created for 14 complications (Superficial Surgical Site Infection (SSI), Deep SSI, Organ/Space SSI, Pneumonia, Pulmonary Embolism (PE), Deep Venous Thrombosis (DVT), Urinary Tract Infection (UTI), Stroke/Cerebrovascular accident (CVA), Myocardial Infarction (MI), Renal Failure, Cardiac Arrest (CA), Re-operation, Sepsis, and Death within 30 days of surgery). Model summaries were used to identify significant variables with a Bonferroni correction applied. Results: A total of 3956 adults met inclusion criteria and were included in analysis. The most common complications were UTI (5.2%), death (4.1%), and pneumonia (3.4%). Complications typically occurred within 14 days after surgery, except for SSI, which occurred between post-op days 11 and 24. Conclusions: Distal femur fractures are a substantial source of morbidity and mortality in the older adult population. Our findings underscore the need for comprehensive preoperative risk assessment and patient management strategies to mitigate the impact of identified risk factors in this vulnerable population.

2.
Osteoporos Int ; 34(7): 1241-1248, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37093238

ABSTRACT

Upper extremity (UE) fractures are prevalent age-related fractures, and stair-associated falls are a common mechanism for these injuries. Our study has identified an increasing incidence of stair-related UE fractures and associated hospitalization rates among the older United States population between 2012-2021. Targeted prevention efforts should be implemented by health systems. INTRODUCTION: To analyze United States (US) emergency department trends in upper extremity stair-related fractures among older adults and investigate risk factors associated with hospitalization. METHODS: We queried the National Electronic Injury Surveillance System (NEISS) for all stair-related fracture injuries between 2012 and 2021 among adults 65 years or older. The US Census Bureau International Database (IDB) was analyzed to calculate incidence rates. Descriptive analysis, linear regression analysis, and multivariate regression analysis were used to interpret the collected data. RESULTS: Our analysis estimated 251,041 (95% CI: 211,678-290,404) upper extremity stair-related fractures among older adults occurred between 2012 and 2021. The primary anatomical locations were the humeral shaft (27%), wrist (26%), and proximal humerus (18%). We found a 56% increase in injuries (R2 = 0.77, p < 0.001), 7% increase in incidence per 100,000 persons (R2 = 0.42, p < 0.05), and an 38% increase in hospitalization rate (R2 = 0.61, p < 0.01) during the 10-year study period. Women sustained the majority of fractures (76%) and most injuries occurred in homes (89%). Advanced age (p < 0.0001), males (p < 0.0001), proximal humerus fractures (p < 0.0001), humeral shaft fractures (p < 0.0001), and elbow fractures (p < 0.0001) were associated with increased odds of hospitalization after injury. CONCLUSION: Stair-related UE fracture injuries, incidence, and hospitalization rates among older adults are increasing significantly, particularly among older females. Improving bone health, optimizing functional muscle mass, and "fall-proofing" homes of older age groups may help mitigate the rising incidence of these injuries.


Subject(s)
Arm Injuries , Fractures, Bone , Shoulder Fractures , Male , Humans , Female , United States/epidemiology , Aged , Incidence , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Arm Injuries/complications , Arm Injuries/epidemiology , Upper Extremity , Hospitalization
3.
Int J Orthop Trauma Nurs ; 47: 100974, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36399973

ABSTRACT

INTRODUCTION: After discovering a low incidence of delirium for hip fracture patients at our institution, we evaluated if this was due to underreporting and, if so, where process errors occurred. METHODS: Hip fracture patients aged ≥60 with a diagnosis of delirium were identified. Chart-Based Delirium Identification Instrument (CHART-DEL) identified missed diagnoses of delirium. Process maps were created based off staff interviews and observations. RESULTS: The incidence of delirium was 15.3% (N = 176). Within a random sample (n = 98), 15 patients (15.5%) were diagnosed, while 20 (24.7%) went undiagnosed despite evidence of delirium. Including missed diagnoses, delirium prevalence was higher in the sample compared to all patients (35.7% vs 15.3%, p < 0.001). Most missed diagnoses were due to failure in identifying delirium (60%) or failure in documenting/coding diagnosis (20%). The prevalence of baseline cognitive impairment was higher in undiagnosed delirium patients versus correctly diagnosed patients (80% vs 20%, p = 0.001). CONCLUSIONS: Our institution significantly underreports delirium among hip fracture patients mainly due to; (1) failure to identify delirium by the clinical staff, and (2) failure to document/code diagnosis despite correct identification. Baseline cognitive impairment can render delirium diagnosis challenging. These serve as targets for quality improvement and hip fracture care enhancement.


Subject(s)
Delirium , Hip Fractures , Humans , Delirium/diagnosis , Delirium/epidemiology , Quality Improvement , Hip Fractures/complications , Hip Fractures/psychology , Incidence , Risk Factors
4.
Geriatr Orthop Surg Rehabil ; 13: 21514593221135480, 2022.
Article in English | MEDLINE | ID: mdl-36310893

ABSTRACT

Introduction: Intertrochanteric (IT) fractures that fail fixation are traditionally treated with arthroplasty, introducing significant risk of morbidity and mortality in frail older adult patients. Revision fixation with cement augmentation is a relatively novel technique that has been reported in several small scale international studies. Here we report a clinical series of 22 patients that underwent revision fixation with cement augmentation for IT fracture fixation failure. Methods: This retrospective case series identified all patients that underwent revision intramedullary nailing from 2018 to 2021 at two institutions within a large metropolitan healthcare system. Demographics, injury characteristics, Charlson Comorbidity Index score, and surgical characteristics were extracted from the electronic medical record. Outcomes were extracted from the electronic medical record and included radiographic findings, pain, functional outcomes, complications, and mortality. Results: Average follow-up after revision surgery was 15.2 ± 10.6 months. Twenty patients (90.9%) reported improved pain and achieved union or progressive healing after surgery. Most of these patients regained some degree of independent ambulation (19 patients, 86.4%), with only 5 patients (22.7%) requiring increased assistance for their activities of daily living (ADLs). One-year mortality was 13.6% (3 patients). Of the 5 patients (22.7%) that experienced complications, 2 patients (9.1%) required revision hemiarthroplasty for subsequent fixation failure. The other 3 patients did well when complications resolved. Conclusions: Revision fixation with cement augmentation can be an effective, safe, cost-effective alternative to arthroplasty for the management of cases involving non-infected failed IT fracture fixation with implant cut-out or cut-through limited to the femoral head in older adult patients that have appropriate acetabular bone stock.

5.
Trauma Case Rep ; 41: 100686, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35942321

ABSTRACT

Although fractures of the proximal humerus are common among older adults, open fractures following low-energy trauma are exceptionally rare. Prior studies have alluded to the existence of this injury, but there are no detailed reports on its presentation, management, or long-term follow-up. We present the case of a 78-year-old man that sustained a suspiciously open proximal humerus fracture of the dominant hand following a fall down a few stairs. Management consisted of early intravenous antibiotics followed by open reduction and internal fixation with irrigation and debridement. Intraoperative soft tissue assessment revealed a wound extending from bone to skin. The patient suffered no complications, regained full function of his arm, and is pain free. Considering the rarity of this injury and its potential for highly morbid complications, this case serves as a reminder that we should continue to have a low suspicion threshold for open fracture when punctures or lesions are present around proximal humerus fractures, even for low-energy injuries. Prompt and thorough examination, initiation of antibiotics, and surgical intervention are keys to providing best care for this uncommon injury.

6.
Trauma Case Rep ; 37: 100577, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35005160

ABSTRACT

CASE: We present the case of a 92-year-old woman who developed a medial femoral circumflex artery (MFCA) pseudoaneurysm intraoperatively while obtaining reduction during intramedullary nailing (IMN) for intertrochanteric fracture. CONCLUSIONS: Pseudoaneurysms are rare vascular complications in hip fracture surgery. Early recognition of signs and symptoms of this phenomenon are essential for diagnosis and treatment. Close post-operative monitoring and serial hemoglobin should be considered for unexplained intra-operative bleeding. A low threshold for angiography should be entertained if active bleeding and clinical decompensation occur during instrumented percutaneous pertrochanteric fracture reduction. This patient underwent conventional angiography with successful coil embolization and exclusion of the MFCA pseudoaneurysm.

7.
OTA Int ; 5(1): e165, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34964041

ABSTRACT

OBJECTIVES: The goal of this study was to investigate whether the COVID-19 pandemic has affected hip fracture care at a Level I Trauma hospital. The secondary goal was to summarize the published hip fracture reports during the pandemic. DESIGN: A retrospective cohort study. SETTING: Level I Trauma Center. PATIENTS/PARTICIPANTS: Eighty-six operatively treated hip fracture patients age ≥65 years, occurring from January 17 to July 2, 2020. INTERVENTION IF ANY: N/A. MAIN OUTCOME MEASUREMENTS: We defined 3 phases of healthcare system response: pre-COVID-19 (period A), acute phase (period B), and subacute phase (period C). The primary outcome was 30-day mortality. Clinical outcomes including time to surgery (TTS) and length of stay (LOS) were extracted from the electronic medical record. RESULTS: Twenty-seven patients from Period A, 27 patients from Period B, and 32 patients from Period C were included. The 30-day mortality was not statistically different. The mean TTS was 20.0 +/- 14.3 hours and was the longest in Period C (22.1 +/- 9.8 hours), but the difference was not statistically significant. The mean LOS was 113.0 +/- 66.2 hours and was longest in Period B (120.9 +/- 100.6 hours). However, the difference was not statistically significant. CONCLUSIONS: The 30-day mortality, TTS, and LOS were not statistically different across multiple phases of pandemic at a level 1 trauma center. Our results suggest that we successfully adapted new protocol changes and continued to provide evidence-based care for hip fracture patients. Our results were comparable with that of other authors around the world.

8.
Orthop Clin North Am ; 52(4): 381-401, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34538350

ABSTRACT

Approximately 4.1% of all fractures in the elderly involve the elbow. Most elbow injuries in geriatric patients occur as the result of low-energy mechanisms such as falls from standing height. Elbow injuries in elderly patients present complex challenges because of insufficient bone quality, comminution, articular fragmentation, and preexisting conditions, such as arthritis. Medical comorbidities and baseline level of function must be heavily considered in surgical decision making.


Subject(s)
Elbow Injuries , Elbow Joint , Elbow , Humeral Fractures , Radius Fractures , Ulna Fractures , Aged , Elbow/surgery , Elbow Joint/surgery , Fracture Fixation, Internal , Humans , Humeral Fractures/diagnosis , Humeral Fractures/therapy , Joint Dislocations/diagnosis , Joint Dislocations/therapy , Olecranon Process/injuries , Radius Fractures/diagnosis , Radius Fractures/therapy , Ulna Fractures/diagnosis , Ulna Fractures/therapy
9.
Geriatr Orthop Surg Rehabil ; 12: 21514593211006692, 2021.
Article in English | MEDLINE | ID: mdl-33868768

ABSTRACT

OBJECTIVES: To better elucidate how the COVID-19 pandemic has affected the operatively treated geriatric hip fracture population and how the health care system adapted to pandemic dictated procedures. DESIGN: Retrospective cohort study. SETTING: A community hospital. PARTICIPANTS: Individuals ≥65 years of age presented with a proximal femoral fracture from a low-energy mechanism undergoing operative treatment from January 17, 2020 to July 2, 2020 (N = 125). MEASUREMENTS: We defined 3 phases of healthcare system response: pre-COVID-19, acute phase, and subacute phase. Thirty-day mortality, time to operating room (OR), length of stay, time to start physical therapy, perioperative complications, delirium rate, hospice admission rate, discharge dispositions, readmission rate, and the reason of surgery delay were assessed. RESULTS: The number of hip fractures has remained constant during the pandemic. The 30-day mortality rate, time to OR, and length of stay were higher in the pandemic compared to the pre-pandemic. Those who had a longer wait time to OR (≥ 24 hours) had more complications and increased 30-day mortality rates. Some of the surgery delays were related to OR unavailability as a consequence of the COVID-19 pandemic. Surgery was delayed in 3 patients who were on direct oral anticoagulants (DOACs) in pandemic but none for pre-pandemic period. CONCLUSION: This is the first study to compare the effect of the acute and subacute phases of the pandemic on uninfected hip fracture patients. In the age of COVID-19, to provide the best care for the vulnerable geriatric orthopedic populations, the healthcare system must adopt new protocols. We should still aim to promote prompt surgical care when indicated. It is important to ensure adequate resource availability, such as OR time and staff so that hip fracture patients may continue to receive rapid access to surgery. A multidisciplinary approach remains the key to the management of fragility hip fracture patients during the pandemic.

10.
J Shoulder Elbow Surg ; 27(4): 667-673, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29555052

ABSTRACT

BACKGROUND: The purposes of this study were (1) to determine how supine versus upright patient position affects the measurement of diaphyseal clavicle fracture displacement, (2) to describe the incidence of progressive displacement in the peri-injury period, and (3) to investigate variables associated with the progressive displacement. METHODS: Between 2013 and 2015, patients aged 14 years or older presenting with a diaphyseal clavicle fracture within 7 days of injury were included (N = 50). A well-defined radiographic protocol was established. Nine patients underwent surgery after the second follow-up, and the remaining 41 patients, who did not undergo surgery, received the full complement of measures at the first, second, and third follow-up time points. The second follow-up (8-21 days after injury) and third follow-up (22-60 days after injury) had the same defined radiographic protocol as the first visit. The amount of displacement and angulation was measured in both the supine and upright positions on the initial injury radiographs and subsequent follow-up radiographs. RESULTS: Vertical translation was 2.4 mm (95% confidence interval, 1.8-3.0 mm) greater and angulation was 3.9° (95% confidence interval, 3.3°-4.6°) greater in the upright position. Progressive displacement occurred in 16 patients (32%). Older age (P = .015) and ipsilateral shoulder girdle or chest wall injury (P = .007) were significantly associated with progressive displacement. CONCLUSIONS: Upright radiographs evaluate maximal displacement in diaphyseal clavicle fractures. Close follow-up of nonoperatively treated clavicle fractures is warranted. Progressive displacement was more likely in older patients and/or those who had ipsilateral shoulder girdle or chest wall injury.


Subject(s)
Clavicle/diagnostic imaging , Clavicle/injuries , Diaphyses/diagnostic imaging , Diaphyses/injuries , Fracture Dislocation/diagnostic imaging , Patient Positioning , Adolescent , Adult , Age Factors , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Radiography , Thoracic Injuries/complications , Young Adult
11.
Curr Eye Res ; 42(12): 1707-1712, 2017 12.
Article in English | MEDLINE | ID: mdl-28937857

ABSTRACT

PURPOSE: Laser speckle flowgraphy (LSFG) can measure blood flow in the ocular fundus. We analyzed the relationship between retinal blood flow and panretinal photocoagulation (PRP) in diabetic retinopathy. METHODS: This retrospective observational study examined the eyes of 35 patients with proliferative diabetic retinopathy (PDR) or non-PDR (NPDR). PRP was performed using a pattern scan laser. Using LSFG, blood flow was evaluated as the mean blur rate (MBR) or the relative flow volume (RFV). We also evaluated MBR in the vessels of the optic nerve head (MBR-V), RFV at the first retinal artery (RFV-A), and RFV at the first retinal vein (RFV-V) before bifurcation. Blood flows were measured prior to treatment initiation, during each PRP session, and after PRP. RESULTS: The total number of laser spots created was 4258 ± 461. Regression of neovascular activity at 6 months after PRP occurred in 29 (82.85%) eyes. MBR-V significantly decreased to 83.9 ± 16% (p = .0039), 79.3 ± 21% (p = .0001), and 73.5 ± 26% (p = .0001) after the first, second, and third PRP treatment sessions. MBR-V was also reduced to 75.0 ± 25% (p = .0001), 75.0 ± 25% (p = .0001), and 80.3 ± 22% (p = .0001) at 1, 3, and 6 months following PRP. During and at 6 months after the PRP treatments, RFV-A and RFV-V were also significantly reduced (p< .01). CONCLUSIONS: During and after PRP treatments using pattern scan laser, retinal blood flow was reduced. Retinal blood flow may be an auxiliary measurement for effectively evaluating PRP or PDR.


Subject(s)
Diabetic Retinopathy/physiopathology , Laser Coagulation , Retinal Vessels/physiology , Adult , Aged , Arterial Pressure/physiology , Blood Flow Velocity/physiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Retinopathy/surgery , Female , Humans , Intraocular Pressure/physiology , Laser-Doppler Flowmetry , Male , Middle Aged , Regional Blood Flow/physiology , Retrospective Studies
12.
Minn Med ; 100(2): 40-44, 2017 Mar.
Article in English | MEDLINE | ID: mdl-30428185

ABSTRACT

Falls are a serious concern for older adults as they frequently result in injury, disability and even death. In older adults in Minnesota, the number and rate of hospital-treated falls have been increasing, for both males and females. The purpose of this study was to estimate trends in falls among older adults in Minnesota, and to examine whether there is an association between severe outcomes of falls and predictors. We investigated hospital-treated (both emergency department treatment and hospitalizations) falls among adults 65 years and older in Minnesota between 2010 and 2014, using hospital discharge data from the Minnesota Hospital Association. In total, 199,364 cases were identified; this represents a rate of 5,281.4/100,000 during the five-year period. We found the number of hospital-treated falls increased each year by 1,820 cases on average, for an average rate increase of 108.3/100,000 per year. The rate for falls with no comorbidities decreased, while the rate for falls with one or more comorbidities increased: Also, comorbidities were more likely among hospitalized and/ or fatal cases than among nonhospitalized and/or nonfatal cases. The most frequent principal injury diagnoses associated with falls included fractures (31.7% of total hospital-treated falls), superficial wounds/contusions (14.7%), open wounds (10.9%) and traumatic brain injuries (TBIs) (3.9%). The most frequent type of fracture was hip fracture (29.1 %). Additional complications commonly occurring during hospital treatment of injury resulting from a fall included urinarytract infection (7.2%), pneumonia (2.2%), pressure ulcer (1.2%) and sepsis (0.9%). Among these, sepsis had the highest odds ratio of 9.9 for death. These data show the burden of falls is greatest among those who are 85 and older and/or who have one or more comorbidities.


Subject(s)
Accidental Falls/statistics & numerical data , Chronic Disease/epidemiology , Emergency Service, Hospital/statistics & numerical data , Hospitalization/statistics & numerical data , Aged , Aged, 80 and over , Chronic Disease/trends , Comorbidity , Correlation of Data , Cross-Sectional Studies , Emergency Service, Hospital/trends , Hospitalization/trends , Humans , Minnesota , Patient Discharge/statistics & numerical data , Utilization Review/statistics & numerical data
13.
Nat Commun ; 7: 12503, 2016 08 16.
Article in English | MEDLINE | ID: mdl-27527664

ABSTRACT

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration.


Subject(s)
Annulus Fibrosus/physiology , Homeodomain Proteins/metabolism , Intervertebral Disc/physiology , Regeneration , Adult , Animals , Annulus Fibrosus/metabolism , Cells, Cultured , Female , Gene Expression Regulation , Homeodomain Proteins/genetics , Humans , Intervertebral Disc/metabolism , Male , Mesenchymal Stem Cells/metabolism , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Young Adult
14.
Curr Eye Res ; 41(10): 1326-1330, 2016 10.
Article in English | MEDLINE | ID: mdl-27002346

ABSTRACT

PURPOSE: To investigate the corneal toxicity of three combined antiglaucoma topical eyedrops using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). METHODS: Corneal TER changes after a 60-s exposure to latanoprost/timolol with 0.02% benzalkonium chloride (BAC), travoprost/timolol with polyquaternium-1, and dorzolamide/timolol with 0.005% BAC were measured in living rabbits. Corneal damage was also examined by SEM. Hank's balanced salt solution (HBSS) was used as a control. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to latanoprost/timolol with 0.02% BAC. Travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC did not produce any significant decrease in the corneal TER as compared to HBSS control eyes. SEM revealed that superficial cells of corneas treated with latanoprost/timolol with 0.02% BAC were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to travoprost/timolol with polyquaternium-1 or dorzolamide/timolol with 0.005% BAC appeared normal and had normal microvilli under SEM examinations. CONCLUSION: The corneal toxicity of latanoprost/timolol with 0.02% BAC is greater than that of travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC. Latanoprost/timolol contains 0.02% BAC, which may be responsible for the corneal toxicity.


Subject(s)
Antihypertensive Agents/toxicity , Cornea/drug effects , Glaucoma/drug therapy , Administration, Topical , Animals , Antihypertensive Agents/administration & dosage , Cornea/physiopathology , Cornea/ultrastructure , Disease Models, Animal , Electric Impedance , Glaucoma/diagnosis , Glaucoma/physiopathology , Male , Microscopy, Electron, Scanning , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/toxicity , Rabbits
15.
Ocul Surf ; 14(1): 37-42, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26462410

ABSTRACT

PURPOSE: To evaluate acute corneal permeability changes after instillation of benzalkonium chloride (BAC) using a newly developed in vivo less invasive corneal transepithelial electrical resistance (TER) measurement method in animals and humans. METHODS: We previously developed an in vivo method for measuring corneal TER using intraocular electrodes in animals. This method can be used to precisely measure the decline of the corneal barrier function after instillation of BAC. To lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the surface of the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. Corneal TER changes before and after exposure to 0.02% BAC were determined in this study using the new device in both rabbits and humans. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to 0.02% BAC solution in both rabbits and humans (P<.01). The results of this new less invasive method agreed with those of formerly established anterior chamber methods in rabbit experiments. CONCLUSION: This new less invasive corneal TER measurement method enables us for the first time to measure TER of the human cornea, allowing safe and reliable investigation of the direct effect of different eye drop treatments on the corneal epithelium.


Subject(s)
Benzalkonium Compounds/pharmacokinetics , Cell Membrane Permeability/physiology , Epithelium, Corneal/physiopathology , Animals , Electric Impedance , Epithelium, Corneal/metabolism , Male , Preservatives, Pharmaceutical/pharmacokinetics , Rabbits
16.
Cutan Ocul Toxicol ; 35(2): 120-5, 2016.
Article in English | MEDLINE | ID: mdl-26113030

ABSTRACT

PURPOSE: To investigate the corneal toxicity of Xalatan and three latanoprost generics using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). METHODS: Corneal TER changes after a 60-s exposure to Xalatan (latanoprost 0.005% preserved with 0.02% BAC), and latanoprost generics (Latanoprost PF BAC free, Latanoprost Nitten SB containing sodium benzoate and Latanoprost Towa containing 0.01% BAC with sodium chloride polysorbate 80 as additive) were measured in living rabbits. Corneal damage was also examined by SEM. Hank's balanced salt solution (HBSS) was used as a control. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to Xalatan (p < 0.01) and all latanoprost generics (p < 0.01: Latanoprost PF, p < 0.05: Latanoprost Nitten SB, Latanoprost Towa) as compared to HBSS. All latanoprost generics showed less TER decrease in the corneal TER as compared to Xalatan (p < 0.01). SEM revealed that superficial cells of Xalatan-treated corneas were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to HBSS or all latanoprost generics appeared normal and had normal microvilli under SEM examinations. CONCLUSION: The corneal toxicity of Xalatan is greater than that of latanoprost generics. Xalatan contains 0.02% BAC, which may be responsible for the corneal toxicity.


Subject(s)
Benzalkonium Compounds/adverse effects , Drugs, Generic/adverse effects , Epithelium, Corneal/drug effects , Ophthalmic Solutions/adverse effects , Preservatives, Pharmaceutical/adverse effects , Prostaglandins F, Synthetic/adverse effects , Animals , Electric Impedance , Epithelium, Corneal/physiology , Epithelium, Corneal/ultrastructure , Latanoprost , Male , Microscopy, Electron, Scanning , Rabbits
17.
Article in English | MEDLINE | ID: mdl-26291653

ABSTRACT

PURPOSE: To develop a device that is capable of easily measuring corneal transepithelial electrical resistance (TER) and changes in the corneal barrier function. METHODS: We had previously developed an in vivo method for measuring corneal TER using intraocular electrode. This method can be used to precisely measure the decline of the corneal barrier function after instillation of benzalkonium chloride (BAC). In order to lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. TER was then calculated by subtracting the electrical resistance, which lacked the corneal epithelial input, from the whole electrical resistance that was measured between the electrodes. Slit lamp examination and scanning electron microscopy (SEM) were used to determine safety of the new device. Corneal TER changes after exposure to 0.02% BAC were determined using the new device as well as SEM and transmission electron microscopy (TEM). RESULTS: Slit lamp examination before and after exposure of rabbits' corneas to the sensor confirmed safety of the device. SEM examination revealed no difference of the corneal epithelium which exposed to the new device with normal corneas. SEM and TEM pictures revealed damaged microvilli and tight junctions after instillation of 0.02% BAC. TER change after treatment with 0.02%BAC was similar to those determined by the established anterior chamber method. CONCLUSION: We succeeded to develop a less invasive device for corneal TER measurement in vivo in animals. This new device may be applicable in the future for clinical use in humans.


Subject(s)
Epithelium, Corneal/physiology , Epithelium, Corneal/ultrastructure , Plethysmography, Impedance/instrumentation , Plethysmography, Impedance/methods , Animals , Electric Impedance , Electrodes , Electrophysiological Phenomena , Equipment Design , Male , Microscopy, Electron, Scanning , Ophthalmic Solutions/administration & dosage , Rabbits , Slit Lamp
18.
J Orthop Res ; 33(1): 1-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25312837

ABSTRACT

Mohawk homeobox (MKX) has been demonstrated as a tendon/ligament specific transcription factor. The aim of this study was to investigate the role of MKX in ligament/tenogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs). Human BMMSCs were treated with 50 ng/ml BMP-12 or transduced with MKX or scleraxis (SCX) adenoviral vector. Gene expression analysis was performed by quantitative reverse transcribed polymerase chain reaction (qRT-PCR). Rat BMMSCs were seeded in a collagen scaffold and transplanted into a rat Achilles tendon defect model. Tenogenesis related gene expressions and histological features were analyzed. BMP-12 induced tenogenesis in BMMSCs as indicated by increased COL1a1, TNXB, DCN and SCX mRNA, and MKX expression increased simultaneously. Rat BMMSCs enhanced defect repair and were still detectable 3 weeks after transplantation. Increased expressions of COL1a1, TNC and TNMD in vivo were also correlated with upregulated MKX. Adenoviral MKX promoted expression of COL1a1, TNXB, and TNMD in BMMSCs. This study demonstrated that MKX gene expression is enhanced during the tenogenic differentiation of BMMSCs in vitro and in vivo, and the adenoviral overexpression of MKX increases tendon extracellular matrix gene expression and protein production. Thus, MKX is a key factor for tenogenic differentiation of MSCs.


Subject(s)
Bone Marrow Cells/cytology , Cell Differentiation/physiology , Homeodomain Proteins/physiology , Mesenchymal Stem Cells/cytology , Tendons/cytology , Transcription Factors/physiology , Achilles Tendon/injuries , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone Morphogenetic Proteins/pharmacology , Cell Differentiation/genetics , Cells, Cultured , Collagen/metabolism , Decorin/metabolism , Gene Expression Regulation/physiology , Growth Differentiation Factors/pharmacology , Homeodomain Proteins/genetics , Humans , In Vitro Techniques , Membrane Proteins/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Models, Animal , Rats , Rats, Wistar , Tenascin/metabolism , Transcription Factors/genetics , Transduction, Genetic
19.
Cornea ; 33(5): 521-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24619166

ABSTRACT

PURPOSE: The aim of this study was to examine the ophthalmic additives responsible for modulating acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) and investigate the ability of polyoxyethylene hydrogenated castor oil 40 (HCO-40) and polysorbate 80 (PS-80) to reduce the corneal toxicity and antimicrobial effects of BAC. METHODS: Cytotoxicity of the additives, which included glycerin, polyvinyl alcohol, propylene glycol, polyethylene glycol, and PS-80, on rabbit corneal epithelial cells was examined using the cell proliferation assay in the presence and absence of 0.02% BAC. The corneal transepithelial electrical resistance change after a 60-second exposure to HCO-40 or PS-80 mixed with 0.02% BAC was measured in living rabbits. Corneal damage was examined using scanning electron microscopy. The antimicrobial activities of HCO-40 and PS-80 with 0.02% BAC against Staphylococcus aureus, Propionibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae were assessed. RESULTS: Of all the tested additives, only PS-80 could prevent the BAC-induced cytotoxicity. Corneal epithelial barrier function disorder caused by 0.02% BAC was significantly alleviated by either PS-80 or HCO-40 in a concentration-dependent manner. Scanning electron microscopy images showed an improvement of BAC-induced corneal epithelial toxicity after the addition of HCO-40 or PS-80. The antimicrobial effect of the BAC against P. aeruginosa, E. coli, and S. pneumoniae was reduced after adding HCO-40 or PS-80. CONCLUSIONS: HCO-40 and PS-80 reduce acute corneal toxicity and the antimicrobial effect of BAC. Possible interactions between BAC and other additives should be taken into consideration when evaluating the toxicity and antibacterial properties of BAC.


Subject(s)
Anti-Infective Agents, Local/toxicity , Benzalkonium Compounds/toxicity , Castor Oil/analogs & derivatives , Epithelium, Corneal/drug effects , Ophthalmic Solutions/toxicity , Polysorbates/pharmacology , Preservatives, Pharmaceutical/toxicity , Animals , Castor Oil/pharmacology , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Cornea/drug effects , Cornea/ultrastructure , Electric Impedance , Epithelium, Corneal/ultrastructure , Escherichia coli/drug effects , Escherichia coli/physiology , Glycerol/toxicity , Male , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Polyethylene Glycols/toxicity , Polyvinyl Alcohol/toxicity , Propylene Glycol/toxicity , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Rabbits , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/physiology
20.
J Orthop Sci ; 19(1): 172-80, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24166359

ABSTRACT

BACKGROUND: Mohawk (Mkx) is a homeodomain-containing transcription factor that is expressed in various mesoderm-derived tissues, particularly in developing tendons. In this study, we investigate the exact expression pattern and functions of Mkx in forelimbs. METHODS: We analyzed the forelimbs of Mkx knockout mice [from embryonic day (E) 18.5 to postnatal day (P) 28 weeks] by using knocked-in Venus signals, Masson trichrome staining, and hematoxylin and eosin (H&E) staining. RESULTS: We detected Venus signals in forelimb tendons, pulleys, and volar plates (VPs) in P21 mice. In-depth histological analysis showed that compared to the wild-type mice, the Mkx knockout mice showed significant hypoplasia in the flexor digitorum profundus tendons from E18.5. The VPs and pulleys appeared normal until P0; however, by P14, they became increasingly thicker in Mkx-null mice compared to wild-type mice. The fiber alignment was particularly disrupted in VPs of Mkx-null mice. CONCLUSIONS: These results suggest that Mkx is an important regulator of the differentiation of VPs and pulleys, as well as of tendon differentiation.


Subject(s)
Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Morphogenesis/genetics , Palmar Plate/growth & development , RNA, Messenger/genetics , Tendons/growth & development , Animals , Animals, Newborn , Cell Differentiation , Disease Models, Animal , Forelimb , Gene Knockout Techniques , Homeodomain Proteins/biosynthesis , Immunohistochemistry , Mice , Mice, Knockout , Palmar Plate/pathology , Phenotype , Tendons/pathology , Transcription, Genetic
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