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1.
J Arthroplasty ; 35(6): 1658-1661, 2020 06.
Article in English | MEDLINE | ID: mdl-32094013

ABSTRACT

BACKGROUND: The direct anterior (DA) approach is becoming increasingly popular for primary total hip arthroplasty (THA). The aim of this study is to evaluate early postoperative complication and revision rates based on surgical approach, comparing DA, posterolateral (PL), and direct superior (DS) approaches. METHODS: After institutional review board approval, a total joint arthroplasty database from a single institution was used to identify all patients who underwent elective primary THA between July 2013 and November 2017 with a DA, PL, or DS hip approach. Patients were followed for complications out to 90 days postsurgery. Patients were divided into groups based on surgical approach and compared on length of stay, discharge disposition, and 90-day complication and revision rates. RESULTS: There were 5341 THA procedures performed, with 3162 PL, 1846 DA, and 333 DS approaches. Length of stay was shorter for DS (1.7 ± 0.9 days) and DA (1.8 ± 0.9 days) than for PL approaches (2.3 ± 1.4 days, P < .001) The DS approach had the highest rate of home discharges (93.1%), but the highest short-term revision rate (1.5%, P = .011). The DA approach had the lowest intraoperative fracture rate (0.1%, P = .019) but the highest incidence of postoperative fractures (1.3%, P = .021). There were no differences in readmission (P = .056), 90-day events (P = .062), emergency department visits (P = .210), dislocations (P = .090), combined perioperative fractures (P = .289), venous thromboembolic events (P = .059), or acute infection rates (P = .287). CONCLUSION: In the era of bundled payments, the DA, PL, and DS approaches can all be effectively used. LEVEL OF EVIDENCE: Level III; retrospective comparative study.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Hip/adverse effects , Humans , Length of Stay , Patient Discharge , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
2.
J Arthroplasty ; 35(5): 1402-1406, 2020 05.
Article in English | MEDLINE | ID: mdl-31924488

ABSTRACT

BACKGROUND: The purpose of this study is to compare open reduction and internal fixation (ORIF) to distal femoral replacement (DFR) for treatment of displaced periprosthetic distal femur fractures. METHODS: We identified 72 patients with minimum 2-year follow-up following a displaced periprosthetic distal femur fracture: 50 were treated with ORIF and 22 with DFR. Outcomes were assessed with multivariate regression analysis and include Knee Society Scores (KSS), infection rates, revision incidence, and mortality. RESULTS: Patients treated with DFR had a higher Charlson comorbidity index (5.2 vs 3.8; P = .006). The mean postoperative KSS were similar between groups, but the Knee Society Functional Scores were higher in the ORIF group (P = .01). Six ORIF patients (12%) and 3 DFR patients (14%) underwent a revision surgery (P = .1). In the ORIF group, 3 revisions were associated with periprosthetic infection, and 3 revisions occurred for aseptic nonunion. In the DFR group, 1 infection was treated with irrigation and debridement, and 2 cases of patellar maltracking resulted in 1 liner exchange with soft tissue release and 1 femoral revision for malrotation. More patients in the ORIF group required repeat revisions, with twice as many total revisions (P < .001). Six ORIF patients and 7 DFR patients died within 2 years (P = .26). CONCLUSION: The Knee Society Functional Score favored ORIF, but the total incidence of revision was higher in the ORIF cohort. Given the high mortality and the substantial risk of reoperation in both groups, additional studies are needed regarding the prevention of and optimal treatment for patients with periprosthetic distal femur fractures.


Subject(s)
Arthroplasty, Replacement, Knee , Femoral Fractures , Periprosthetic Fractures , Arthroplasty, Replacement, Knee/adverse effects , Femoral Fractures/epidemiology , Femoral Fractures/etiology , Femoral Fractures/surgery , Femur/surgery , Fracture Fixation, Internal/adverse effects , Humans , Periprosthetic Fractures/epidemiology , Periprosthetic Fractures/etiology , Periprosthetic Fractures/surgery , Reoperation , Retrospective Studies , Treatment Outcome
3.
Orthopedics ; 42(6): e528-e531, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31185123

ABSTRACT

Primary total joint arthroplasty (TJA) of the hip and knee are effective procedures for improving pain and function in patients with arthritis. This study examined whether order of surgery (TKA or THA first) affects length of stay (LOS) and discharge disposition among patients with coexisting knee and hip arthritis. A total joint arthroplasty database review was performed to collect all available data for arthroplasties performed at 2 campuses of a single institution between July 2013 and April 2017. Inclusion criteria were patients who underwent both primary THA and TKA within 18 months and were age 18 years or older. Patients were divided into 2 groups based on whether THA or TKA was performed first. For all procedures, the following data were collected: age, body mass index (BMI), time between cases, LOS, discharge disposition, and the number of 90-day adverse postoperative events. Adverse 90-day events included deep infection, fracture, hardware failure, urinary tract infection, other return to the operating room, emergency department visit, readmission, or death. A total of 211 patients underwent both THA and TKA within 18 months; 124 patients underwent THA first and 87 underwent TKA first. There was no difference in age or BMI between the 2 groups. There was a significantly longer time between the first and second arthroplasty in patients with TKA first by a mean of 2 months (P=.001). There was no difference in 90-day adverse postoperative events following THA whether done first or second (P=.371), and no difference in 90-day events following TKA whether done first or second (P=.524). There was no difference in discharge disposition (P=.833 and P=.395) or LOS (P=.695 and P=.473) between groups for the first or second procedure, respectively. In a patient with coexisting hip and knee arthritis, the current results do not support recommending THA or TKA first based on cost related to LOS and discharge disposition. [Orthopedics. 2019; 42(6):e528-e531.].


Subject(s)
Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Knee/methods , Length of Stay , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/surgery , Aged , Costs and Cost Analysis , Databases, Factual , Female , Humans , Male , Middle Aged , Osteoarthritis, Hip/complications , Osteoarthritis, Knee/complications , Patient Discharge , Postoperative Period , Risk Factors , Treatment Outcome
4.
J Arthroplasty ; 34(6): 1273-1278, 2019 06.
Article in English | MEDLINE | ID: mdl-30853157

ABSTRACT

BACKGROUND: Dual-mobility (DM) total hip arthroplasty (THA) systems are designed to increase stability while potentially avoiding problems associated with large femoral heads. Complications of these systems are not yet fully understood. This study aims at characterizing in vivo performance of DM hip systems and assessing modes of clinical failure. METHODS: Under an institutional review board-approved implant retrieval protocol, 18 DM THA systems from 17 patients were included. Implants were graded at the head-neck junction for fretting and corrosion based on the system of Goldberg et al. Components were also macroscopically examined for different damage modes. Demographics and surgical data were collected from medical records, and radiographs were assessed for component positioning. Data were analyzed through Spearman rank-order correlation and Mann-Whitney U-tests, with α = 0.05. RESULTS: The average length of implantation was 13.4 months with mild to moderate fretting corrosion damage. Polyethylene (PE) liners exhibited edge deformation, scratching, and pitting damage. Metallic components exhibited burnishing and scratching damage. Summed fretting and corrosion scores were strongly correlated (ρ = 0.967, P < .0001). Summed corrosion score was moderately correlated with presence of embedding on the PE liner (ρ = 0.690, P = .017). PE liner abrasion and edge deformation of the femoral stem taper were moderately positively correlated (ρ = 0.690, P = .017). Fretting and corrosion damage were not significantly correlated with patient demographics or radiographic positioning of implants. There were no differences in scores between modular and monoblock designs. CONCLUSION: These findings demonstrate that dual-mobility THA systems may be susceptible to the same fretting and corrosion damage observed in traditional modular THA systems. Future studies are needed to confirm these results and clinical significance.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Femur Head/surgery , Femur/surgery , Hip Prosthesis/adverse effects , Aged , Aged, 80 and over , Corrosion , Female , Humans , Male , Metals , Middle Aged , Orthopedics , Polyethylene , Prosthesis Design , Prosthesis Failure , Range of Motion, Articular , Registries , Retrospective Studies
5.
Orthopedics ; 41(6): e747-e755, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30321439

ABSTRACT

Patella fractures comprise 1% of all fractures. Treatment options vary based on fracture displacement, classification, and patient factors. Traditionally, nonoperative treatment has been reserved for nondisplaced fractures. Many operative treatments are available with differing indications and levels of success. Tension band constructs have been the most commonly employed approach to fixation, with cerclage wiring for comminuted fractures. Recently, plate fixation of patella fractures has become more popular. Plating constructs offer a low-profile design with stable fixation, allowing for earlier mobilization and potentially improved functional outcomes. Data regarding the long-term outcomes of plating techniques are limited, and further studies are needed. [Orthopedics. 2018; 41(6):e747-e755.].


Subject(s)
Fracture Fixation, Internal/methods , Fractures, Bone/therapy , Fractures, Comminuted/surgery , Knee Injuries/therapy , Patella/injuries , Patella/surgery , Bone Plates , Bone Wires , Humans , Patella/anatomy & histology
6.
J Orthop Surg (Hong Kong) ; 26(3): 2309499018808356, 2018.
Article in English | MEDLINE | ID: mdl-30369289

ABSTRACT

Polyethylene (PE) remains the gold standard for the articulating surface in hip and knee arthroplasty. To increase arthroplasty longevity and improve wear resistance, newer versions of PE have been designed with resultantly different wear properties. Highly cross-linked polyethylene (HXLPE) is used in total hip arthroplasty with excellent outcomes; however, its use in total knee arthroplasty (TKA) remains conflicting. This review summarizes biomechanical and wear properties, clinical outcomes, and cost of polyethylene inserts in TKA. Simulation studies have convincingly shown decreased wear and oxidation rates with HXLPE when compared to conventional polyethylene (CPE). Registry results have been conflicting, and short- to midterm clinical studies have not demonstrated a significant difference between HXLPE and CPE. The cost of HXLPE inserts is higher than CPE. Long-term clinical data are lacking and further studies are warranted to evaluate the role of HXLPE in TKA.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Materials Testing/methods , Polyethylene , Registries , Humans , Prosthesis Design , Reproducibility of Results
7.
J Arthroplasty ; 33(11): 3416-3421, 2018 11.
Article in English | MEDLINE | ID: mdl-30057269

ABSTRACT

BACKGROUND: More emphasis is being placed on patient-reported outcome measures (PROMs), but the myriad of PROMs makes standardization and cross-study comparison difficult. As the era of big data and massive total joint registries matures, it will be critical to identify and implement the best PROMs. METHODS: All abstracts published in the years 2004, 2009, 2014, and 2016 in the Journal of Bone and Joint Surgery-American volume, the Bone and Joint Journal, Clinical Orthopedics and Related Research, and the Journal of Arthroplasty were reviewed. A PubMed search was performed with filters limiting results only to total knee, total hip, and unicompartmental knee arthroplasty articles with available abstracts. Each abstract was reviewed to identify all PROMs. Trends over time were evaluated using the Cochran-Armitage test. In the non-trend analysis, Pearson chi-square tests and one-way analysis of variance were performed. RESULTS: A total of 42 unique PROMs were used 1073 times across 644 studies. The number of PROMs in these 4 journals increased from 97 in 2004 to 228 in 2016 (P < .0001). The proportion of articles with more than one PROM increased from 20.6% in 2004 to 47.8% in 2016 (P = .0001). The most common PROMs used in total knee, total hip, and unicompartmental knee arthroplasty studies were the Knee Society Score, the Harris Hip Score, and the Oxford Knee Score, respectively. CONCLUSION: Providers and registries should consider the relative prevalence of published outcome measures when selecting which PROMs to use, to better facilitate future cross-study comparison.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Orthopedics/trends , Patient Reported Outcome Measures , Humans , Knee Joint/surgery , Orthopedics/statistics & numerical data , Range of Motion, Articular , Treatment Outcome
8.
Orthopedics ; 41(3): 171-176, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29570760

ABSTRACT

Aspirin and unfractionated heparin (UH) are accepted options for venous thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA). The use of aspirin in addition to UH in preventing VTE after TJA has yet to be studied. The primary objective of this study was to determine VTE rates in patients receiving aspirin monotherapy and those receiving aspirin and UH combination therapy immediately following TJA. A TJA database from a single hospital system was retrospectively reviewed to identify all patients who underwent primary hip or knee arthroplasty from 2013 to 2016. Patients were divided into 3 groups based on postoperative VTE chemoprophylaxis: aspirin only, aspirin with 1 dose of UH, and aspirin with multiple doses of UH. There were 5350 patients included: 1024 aspirin only, 1695 aspirin plus 1 dose of UH, and 2631 aspirin plus multiple doses of UH. Deep venous thrombosis and pulmonary embolus rates did not vary significantly between groups (deep venous thrombosis: 1.1%, 0.9%, and 1.2%, respectively, P=.701; pulmonary embolus: 0.3%, 0.3%, and 0.2%, respectively, P=.894). Transfusion rates were significantly greater with 1 dose of UH (1.8%) and multiple doses of UH (4.3%) compared with aspirin only (0.9%) (P<.001). Additionally, the postoperative hemoglobin decreased significantly more postoperatively with the use of UH (P<.001). Aspirin and UH combination therapy did not decrease VTE incidence compared with aspirin monotherapy. Additionally, there was greater perioperative blood loss and an increased rate of blood transfusion in patients receiving UH. On the basis of these findings, the authors do not recommend UH as an additional mode of VTE prophylaxis when prescribing aspirin after elective TJA. [Orthopedics. 2018; 41(3):171-176.].


Subject(s)
Anticoagulants/therapeutic use , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Aspirin/therapeutic use , Heparin/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Venous Thromboembolism/prevention & control , Aged , Blood Loss, Surgical , Blood Transfusion , Drug Therapy, Combination , Female , Hemoglobins/metabolism , Humans , Male , Middle Aged , Postoperative Period , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Retrospective Studies , Venous Thromboembolism/etiology , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
9.
J Arthroplasty ; 33(2): 320-323, 2018 02.
Article in English | MEDLINE | ID: mdl-28988612

ABSTRACT

BACKGROUND: Simultaneous vs staged bilateral total knee arthroplasty (BTKA) has long been debated. The primary objective of this study was to compare actual hospital costs and complication rates in patients undergoing simultaneous BTKA (simBTKA) and staged BTKA (staBTKA) at a single institution. METHODS: A total joint arthroplasty database from a single hospital was used to identify all patients who underwent primary BTKA from 2013 to 2016 and divided into simultaneous and staged groups. StaBTKA patients were included if both procedures were performed within 1 year by the same surgeon. The combined total hospital cost of both procedures was used, and inpatient rehabilitation (IPR) costs were added for all patients discharged to IPR. RESULTS: There were 225 simBTKA and 337 staBTKA patients. SimBTKA patients were younger (61 ± 8 vs 66 ± 8 years, P < .001), had lower body mass index (31.3 ± 5.9 vs 34.0 ± 7.2, P < .001), were more predominately male (48% vs 38%, P = .029), and more likely to require IPR as compared with staBTKA patients. There was no difference in total hospital cost for simBTKA as compared with staBTKA ($24,596 ± $5652 vs $24,915 ± $5756, P = .586). Complications were more prevalent in the simBTKA group, including venous thromboembolism (5.4% vs 1.4%, P = .006) and blood transfusions (15.8% vs 6.2%, P < .001). CONCLUSION: There were higher complication rates with no significant cost savings in actual hospital costs associated with simBTKA, when accounting for the cost of IPR, as compared with staBTKA. The total cost analysis of simBTKA vs staBTKA, using actual cost data, merits further evaluation.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/economics , Hospital Costs/statistics & numerical data , Osteoarthritis, Knee/surgery , Aged , Arthroplasty, Replacement, Knee/methods , Arthroplasty, Replacement, Knee/statistics & numerical data , Costs and Cost Analysis , Databases, Factual , Female , Humans , Male , Middle Aged , Patient Discharge/statistics & numerical data , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
11.
Clin Orthop Relat Res ; 473(10): 3272-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25800376

ABSTRACT

BACKGROUND: Patients with Parkinson's disease are at increased risk for falls and associated hip fractures as a result of tremor, bradykinesia, rigidity, and postural instability. The available literature is limited and conflicting regarding the optimal surgical treatment and risk for postoperative complications and mortality in this unique patient population. QUESTIONS/PURPOSES: We asked: (1) Is there a difference in mortality after surgical treatment of hip fractures in patients with Parkinson's disease compared with similar patients with hip fractures without Parkinson's disease? (2) Does Parkinson's disease lead to a higher rate of reoperation after operative treatment of femoral neck fractures? (3) Does Parkinson's disease lead to a higher rate of dislocation after hemiarthroplasty for displaced femoral neck fractures, and (4) does the operative approach affect dislocation rates? METHODS: In this case-controlled study, we retrospectively reviewed 141 patients with a diagnosis of Parkinson's disease and a fracture of the femoral neck. Each patient with Parkinson's disease was matched with two control patients (n = 282) without Parkinson's disease stratified by age, sex, American Society of Anesthesiologists classification, and fracture type (nondisplaced/displaced). Clinical outcomes included mortality after surgical intervention, rate of reoperation, dislocation events after hemiarthroplasty, and the rate of failure after internal fixation for nondisplaced fractures. RESULTS: The median survival time of the patients with Parkinson's disease after fracture was 31 months (95% CI, 25-37 months) compared with 45 months (95% CI, 39-50 months) in our control group (p = 0.007). The rate of reoperation for displaced and nondisplaced fractures was higher in the Parkinson's disease group compared with the control group (11% versus 4%; p = 0.005). Failure of fixation for patients treated with internal fixation of nondisplaced femoral neck fractures was significantly higher in the Parkinson's disease group compared with our control group (22% versus 5%; p = 0.01). Dislocation rates after hemiarthroplasty were significantly higher in the Parkinson's disease group compared with the control group (8% versus 1%; p = 0.003). Patients treated with a hemiarthroplasty through an anterolateral approach had a significantly lower dislocation rate compared with those treated with a posterior approach (2% versus 15%; p = 0.002). CONCLUSIONS: Parkinson's disease is an independent predictor of mortality after femoral neck fracture and is associated with an increased rate of dislocation, revision surgery, and failure of internal fixation. Although patients with Parkinson's disease with a nondisplaced or valgus impacted femoral neck fracture may be treated with internal fixation, they are at significantly higher risk of failure of fixation compared with patients without Parkinson's disease. Use of a hemiarthroplasty through an anterolateral approach may reduce the likelihood of requiring a revision operation. LEVEL OF EVIDENCE: Level III, therapeutic study.


Subject(s)
Femoral Neck Fractures/mortality , Femoral Neck Fractures/surgery , Parkinson Disease/complications , Aged, 80 and over , Case-Control Studies , Female , Femoral Neck Fractures/complications , Humans , Male , Postoperative Complications/mortality , Reoperation/statistics & numerical data , Retrospective Studies , Risk Factors
12.
Foot Ankle Int ; 33(10): 870-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23050712

ABSTRACT

BACKGROUND: Diagnosis of syndesmotic injuries is primarily based upon the assessment of ankle radiographs. The purpose of our study was to redefine the radiographic relationships of the ankle syndesmosis based on a large series of normal ankle radiographs in living subjects. METHODS: The study involved 392 patients (218 females, 174 males) with ankle radiographs without known clinical or radiographic evidence of abnormality. Eighty-three of the 392 patients had also had normal contralateral radiographs. Tibiofibular overlap and tibiofibular clear space were measured on anteroposterior (AP) and mortise radiographs. The radiographic measurements were used to calculate means, standard deviations, and intra- and interobserver reliabilities, and compare genders and side-to-side radiographs. RESULTS: The mean overlap was 8.3 mm on the AP and 3.5 mm on the mortise while the mean clear space was 4.6 mm on the AP and 4.3 mm on the mortise view. The least amount of overlap on the AP view was 1.8 mm. On the mortise view, there was a subset of patients that had a complete lack of overlap (less than 0 mm) with the greatest gap noted to be 1.9 mm. The greatest clear space on AP was 8 mm and on the mortise was 7.6 mm. Mortise clear space was the most accurate measure when obtaining contralateral radiographs, with a mean side-to-side difference of 0.7 ± 0.7 mm. CONCLUSION: Lack of overlap on the mortise view can represent a normal variant, which has not been definitively reported in prior investigations. CLINICAL RELEVANCE: Our data form the basis for revised radiographic criteria to evaluate the distal tibiofibular syndesmosis which may influence clinical management of these patients.


Subject(s)
Ankle Joint/diagnostic imaging , Fibula/diagnostic imaging , Tibia/diagnostic imaging , Adolescent , Adult , Aged , Female , Humans , Ligaments, Articular/diagnostic imaging , Male , Middle Aged , Observer Variation , Radiography , Reproducibility of Results , Sex Characteristics , Young Adult
13.
Arthroscopy ; 27(5): 681-94, 2011 May.
Article in English | MEDLINE | ID: mdl-21663724

ABSTRACT

Failure of primary shoulder stabilization procedures is often related to uncorrected anatomic pathology. Orthopaedic surgeons must recognize excessive capsular laxity or large glenohumeral bone defects preoperatively to avoid recurrence of instability. When history, physical examination, and radiographic evaluation are used in conjunction, patients at risk for failure can be identified. The instability severity index score permits precise identification of patients at risk. When treating patients in whom prior surgical intervention has failed, the success of revision procedures correlates to the surgeon's ability to identify the essential pathology and use lesion-specific treatment strategies. Revision procedures remain technically demanding. Keen preoperative and intraoperative judgment is required to avoid additional recurrence of instability after revision procedures, particularly because results deteriorate with each successive operation. Glenoid or humeral defects with greater than 25% bone loss compromise stability provided through the mechanism of concavity compression. These defects must be specifically addressed to avoid recurrence of instability. We prefer anatomic reconstruction techniques combined with capsulolabral repair and, if bone defects are present, anatomic reconstruction with osteochondral allograft.


Subject(s)
Joint Instability/surgery , Shoulder Dislocation/surgery , Shoulder Joint/surgery , Arthroscopy/methods , Bone Transplantation , Cartilage, Articular/injuries , Cartilage, Articular/surgery , Fractures, Bone/complications , Fractures, Bone/surgery , Humans , Joint Capsule/surgery , Joint Instability/diagnosis , Joint Instability/rehabilitation , Physical Examination , Preoperative Care , Randomized Controlled Trials as Topic , Recurrence , Risk Factors , Rotator Cuff/physiopathology , Rotator Cuff Injuries , Scapula/injuries , Severity of Illness Index , Shoulder Dislocation/etiology , Shoulder Dislocation/prevention & control , Shoulder Dislocation/rehabilitation , Shoulder Fractures/complications , Shoulder Fractures/surgery , Stress, Mechanical
14.
Behav Brain Res ; 157(1): 79-90, 2005 Feb 10.
Article in English | MEDLINE | ID: mdl-15617774

ABSTRACT

Previous studies in humans have demonstrated a high co-morbidity between alcoholism and smoking. This co-morbidity between alcohol and nicotine dependence can be attributed, in part, to common genetic factors. In rodents, behavioral and physiological responses to alcohol and nicotine also appear to share common genetic influences. In this report, the genetic correlation between free-choice oral nicotine and oral alcohol consumption was evaluated using an ascending two-bottle choice paradigm in C57BL/6xC3H/HeJ F2 intercross mice. For all concentrations of nicotine (25, 50, and 100 microg/ml) and alcohol (3, 6, and 10%) tested, nicotine consumption was significantly correlated with alcohol consumption. Nicotine consumption at the highest nicotine concentration tested (100 microg/ml) showed low, but significant, correlations with the number of [3H]-cytisine binding sites in the hippocampus (r=0.307) and the number of [125I]-alpha-bungarotoxin binding sites in the cortex (r=-0.328). No significant correlations between alcohol consumption and the number of either [3H]-cytisine or [125I]-alpha-bungarotoxin binding sites was observed. A polymorphism in the nicotinic receptor alpha4 subunit gene, Chrna4, showed a trend with nicotine consumption and a significant association with alcohol consumption in female but not male mice. These results indicate that common genetic factors influence nicotine and alcohol consumption in mice. However, neither individual differences in the expression of [3H]-cytisine or [125I]-alpha-bungarotoxin binding nicotinic receptors nor the polymorphism in Chrna4 likely contribute to the genetic overlap that influences the consumption of both of these drugs of abuse in C57BL/6xC3H/HeJ F2 mice.


Subject(s)
Alcohol Drinking/genetics , Choice Behavior/physiology , Ethanol/metabolism , Nicotine/metabolism , Receptors, Nicotinic/metabolism , Smoking/genetics , Taste/physiology , Alcohol Drinking/metabolism , Alkaloids/genetics , Alkaloids/metabolism , Animals , Azocines/metabolism , Bungarotoxins/metabolism , Cerebral Cortex/metabolism , Drinking/physiology , Female , Hippocampus/metabolism , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Nicotine/antagonists & inhibitors , Polymorphism, Genetic , Quinolizines/metabolism , Receptors, Nicotinic/genetics , Sex Factors , Species Specificity , Taste/genetics , alpha7 Nicotinic Acetylcholine Receptor
15.
J Neurochem ; 91(5): 1138-50, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15569257

ABSTRACT

Mouse alpha4beta2 nicotinic acetylcholine receptors (nAchRs) were stably expressed in HEK293T cells. The function of this stable cell line, termed mmalpha4beta2, was assessed using an aequorin-based luminescence method that measures agonist-evoked changes in intracellular calcium. Agonist-elicited changes in intracellular calcium were due primarily to direct entry of calcium through the alpha4beta2 channel, although release of calcium from intracellular stores contributed approximately 28% of the agonist-evoked response. Agonist pharmacologies were very similar between the mmalpha4beta2 cells and most cell lines that stably express human alpha4beta2 nAchRs. Based on agonist profiles and sensitivity to the antagonist dihydro-beta-erythroidine (DHbetaE), the predominant alpha4beta2 nAchR expressed in the mmalpha4beta2 cells exhibits a pharmacology that most resembles the DHbetaE-sensitive component of 86Rb+ efflux from mouse brain synaptosomes. However, when evaluated with the aequorin assay, the mmalpha4beta2 nAchR was found to be atypically sensitive to blockade by the presumed alpha7-selective antagonist methyllycaconitine (MLA), exhibiting an IC50 value of 31 +/- 0.1 nm. Similar IC50 values have been reported for the MLA inhibition of nicotine-stimulated dopamine release, a response that is mediated by beta2-subunit-containing nAchRs and not alpha7-subunit-containing nAchRs. Consequently, at low nanomolar concentrations, MLA may not be as selective for alpha7-containing nAchRs as previously thought.


Subject(s)
Gene Expression/physiology , Receptors, Nicotinic/physiology , Acetylcholine/pharmacology , Aequorin/metabolism , Animals , Brain/cytology , Brain/drug effects , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cadmium Chloride/pharmacology , Calcium/metabolism , Calcium/pharmacology , Cell Line , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Inhibitors/pharmacology , Extracellular Space/drug effects , Extracellular Space/metabolism , Gene Expression/drug effects , Humans , Inhibitory Concentration 50 , Macrocyclic Compounds , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Nicotinic Agonists/pharmacokinetics , Nicotinic Agonists/pharmacology , Nicotinic Antagonists/pharmacology , Oxazoles/pharmacology , Patch-Clamp Techniques/methods , Pyridines/pharmacokinetics , Pyridines/pharmacology , Radioligand Assay/methods , Receptors, Nicotinic/genetics , Rubidium Radioisotopes/metabolism , Ryanodine/pharmacology , Synaptosomes/drug effects , Synaptosomes/metabolism , Transfection/methods
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