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BACKGROUND: It is not always clear how to treat glenohumeral osteoarthritis, particularly in young patients. The goals of this study were to 1) quantify how patient age, activity level, symptoms, and radiographic findings impact the decision-making of shoulder specialists and 2) evaluate the observer reliability of the Kellgren-Lawrence (KL) grading system for primary osteoarthritis of the shoulder. METHODS: Twenty-six shoulder surgeons were each sent 54 simulated patient cases. Each patient had a different combination of age, symptoms, activity level, and radiographs. Responders graded the radiographs and chose a treatment (non-operative, arthroscopy, hemiarthroplasty, or total shoulder arthroplasty). Spearman correlations and chi square tests were used to assess the relationship between factors and treatments. Sub-analysis was performed on surgical cases. An intra-class correlation (ICC) was used to assess observer agreement. RESULTS: The significant correlations (P<0.01) were: symptoms [0.46], KL grade [0.44], and age [0.11]. In the sub-analysis of operative cases, the significant correlations were: KL grade [0.64], age [0.39], and activity level [-0.10]. The chi square analysis was significant (P<0.01) for all factors, but the practical significance of activity level was minimal. The ICCs were [inter](intra): KL [0.79] (0.84), patient management [0.54]. CONCLUSION: When evaluating glenohumeral osteoarthritis, patient symptoms and KL grade are the factors most strongly associated with treatment. In operative cases, the factors most strongly associated with the choice of operation were the patient's KL grade and age. Additionally, the KL classification demonstrated excellent observer reliability. However, there was only moderate agreement among shoulder specialists regarding treatment, indicating that this remains a controversial topic.
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PURPOSE: Appropriate surgical management for type V complete acromioclavicular (AC) joint dislocation remains controversial. The purpose of this paper is to retrospectively report the clinical and radiographic outcomes of an open surgical technique consisting for AC joint ligamentous and capsular reconstruction using autologous hamstring tendon grafts and semi-permanent sutures. METHODS: Between January 2005 and December 2011, 32 consecutive patients with symptomatic type V complete AC joint dislocation underwent surgical treatment using the same technique. The median time from injury to surgery was 45 days (range 24-90). The average median postoperative clinical and radiographic follow-up time was 30 months (range 24-33). Clinical outcomes measures included the ASES score, the visual analog score (VAS), and subjective patient satisfaction score. Minimum follow-up was 2 years. RESULTS: ASES score increased from a median of 38.2 ± 6.2 preoperative to 92.1 ± 4.7 postoperatively (p ≤ 0.05). The median VAS score improved from 62 mm (range 45-100 mm) preoperatively to 8 mm (range 0-20 mm) at final follow-up (p ≤ 0.05). No patient experienced pain or discomfort with either direct palpation of the AC joint or with cross-body adduction. Final radiographs demonstrated symmetric AC joint contour in 25/32 (78%) patients. Seven patients (22%) radiographically demonstrated superior translation of the distal clavicle relative to the superior margin of the acromion but less than 50% of the clavicular width. 30/32 patients (93%) were able to return to their pre-injury level of work and sports activities. CONCLUSIONS: This novel surgical technique using a free graft and braided suture for simultaneous coracoclavicular ligament and AC joint capsular reconstruction successfully controls superior and posterior translations after type V AC joint dislocation and minimizes the incidence of persistent postoperative AC joint subluxation. LEVEL OF EVIDENCE: Retrospective case series, Level IV.
Assuntos
Articulação Acromioclavicular/lesões , Músculos Isquiossurais/transplante , Cápsula Articular/cirurgia , Luxações Articulares/cirurgia , Ligamentos Articulares/cirurgia , Articulação Acromioclavicular/cirurgia , Adulto , Autoenxertos , Feminino , Humanos , Luxações Articulares/classificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volta ao Esporte , Retorno ao Trabalho , Escala Visual Analógica , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Rupture of the anterior and middle deltoid muscle associated with rotator cuff tear arthropathy (RCA) could result in a definitive loss of shoulder function. The purpose of this study was to evaluate clinical outcomes after a concomitant reverse shoulder arthroplasty (RSA) and deltoid repair under these circumstances. MATERIALS AND METHODS: Between 2006 and 2012, 18 consecutive patients with a mean age of 69.7 years, affected by massive irreparable rotator cuff tear and associated dehiscence or rupture of anterior and middle deltoid muscle underwent this operation through a modified anterosuperior approach. Four patients referred a previous shoulder surgery and deltoid tear was iatrogenic. The other 14 cases had an attritional deltoid tears. The average follow-up was 64 months (range 25-121 months). RESULTS: The mean active anterior elevation passed from a preoperative mean of 53 ± 9.1 (range 45-70) to 132.7 ± 11.6° (85-155°), active external rotation passed from a preoperative mean value of 22.4 ± 3.6° (range 18-26) to an average of 33.7 ± 4.7° (range 30-40°). Mean Constant score increased from 42 ± 6.1 (range 31-51) pre-operatively to 72.3 ± 8.2 (range 57-82) post-operatively. At final review, deltoid contour subjectively was satisfactory to all patients with no palpable defects. CONCLUSION: RSA associated with a repair of deltoid tear could be a viable surgical option in cases of tear involving the anterior and middle deltoid associated with a RCA. Patient with a preoperative chronic axillary nerve neuropathy associated with a deltoid muscle tear should be cautioned about the possibility of lower functional outcomes.
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Artroplastia do Ombro/métodos , Músculo Deltoide/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Amplitude de Movimento Articular/fisiologia , Lesões do Manguito Rotador/cirurgia , Idoso , Estudos de Coortes , Terapia Combinada , Músculo Deltoide/lesões , Feminino , Seguimentos , Humanos , Escala de Gravidade do Ferimento , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/diagnóstico por imagem , Traumatismo Múltiplo/cirurgia , Medição da Dor , Radiografia/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Recuperação de Função Fisiológica , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Lesões do Manguito Rotador/diagnóstico por imagem , Ruptura/cirurgia , Lesões do Ombro/diagnóstico por imagem , Lesões do Ombro/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Arthroscopic transosseous (TO) rotator cuff repair has recently emerged as a new option for surgical treatment of symptomatic rotator cuff tears. Limited data is available regarding outcomes using this technique. This study evaluated midterm clinical outcomes following a novel arthroscopic TO (anchorless) rotator cuff repair technique. MATERIALS AND METHODS: A consecutive series of 107 patients and 109 shoulders underwent arthroscopic TO (anchorless) rotator cuff repair for a symptomatic full-thickness tear. Pre and postoperative range of motion (ROM) was compared at an average of 11.8 months. Postoperative outcome scores were obtained at an average of 38.0 months. Statistical analysis was performed to compare pre and postoperative ROM data. Univariate analysis was performed using Student's t-test to compare the effect of other clinical characteristics on final outcome. RESULTS: Statistically significant improvements were noted in forward flexion, external rotation and internal rotation (P < 0.0001). Average postoperative subjective shoulder value was 93.7, simple shoulder test 11.6, and American Shoulder and Elbow Surgeons (ASES) score 94.6. According to ASES scores, results for the 109 shoulders available for final follow-up were excellent in 95 (87.1%), good in 8 (7.3%), fair in 3 (2.8%), and poor in 3 (2.8%). There was no difference in ROM or outcome scores in patients who underwent a concomitant biceps procedure (tenodesis or tenotomy) compared with those who did not. Furthermore, there was no significant difference in outcome between patients who underwent either biceps tenodesis or tenotomy. Age, history of injury preceding the onset of pain, tear size, number of TO tunnels required to perform the repair, and presence of fatty infiltration did not correlate with postoperative ROM or subjective outcome measures at final follow-up. Two complications and four failures were noted. CONCLUSIONS: Arthroscopic TO rotator cuff repair technique leads to statistically significant midterm improvement in ROM and satisfactory midterm subjective outcome scores with low complication/failure rates in patients with average medium-sized rotator cuff tears with minimal fatty infiltration. Further work is required to evaluate radiographic healing rates with this technique and to compare outcomes following suture anchor repair. LEVEL OF EVIDENCE: Level IV.
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BACKGROUND: The treatment of young patients with glenohumeral arthritis has been challenging. Alternative treatment options include activity modification, arthroscopic débridement, and arthroplasty. Addressing the glenoid during arthroplasty in this population of patients continues to be a significant challenge. In this study, we evaluated the midterm outcomes of hemiarthroplasty with biologic resurfacing of the glenoid with human dermal matrix allograft. METHODS: Between 2004 and 2011, 55 patients underwent hemiarthroplasty and biologic resurfacing of the glenoid with human dermal matrix allograft. The average age was 50 ± 9 years. Subjective evaluation was performed with the Western Ontario Osteoarthritis of the Shoulder Index, American Shoulder and Elbow Surgeons score, visual analog scale, and Single Assessment Numeric Evaluation. Patients returned to the clinic for clinical examination and radiographic evaluation. The average follow-up was 60 months. RESULTS: The average postoperative American Shoulder and Elbow Surgeons score was 76 ± 22, and the Western Ontario Osteoarthritis of the Shoulder Index score was 76% ± 22%. The visual analog scale score was 2.4 ± 2.6. The average preoperative Single Assessment Numeric Evaluation score was 33% ± 22%, which significantly improved to 72% ± 22% postoperatively. Eighty-one percent of the patients were satisfied (10/47) or highly satisfied (28/47) with their result. With radiographic evaluation, the average joint space was 1 ± 1 mm preoperatively and 2 ± 1 mm postoperatively. A total of 5 cases (9.1%) were revised to anatomic total shoulder arthroplasty with implantation of a glenoid component. DISCUSSION: Hemiarthroplasty with biologic resurfacing of the glenoid using human dermal matrix allograft can lead to successful midterm outcomes with satisfactory complication and revision rates. Both patient satisfaction and clinical outcome remain high regardless of radiographic outcome.
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Derme Acelular , Cavidade Glenoide/cirurgia , Hemiartroplastia/métodos , Osteoartrite/cirurgia , Plasma Rico em Plaquetas , Articulação do Ombro/cirurgia , Adulto , Idoso , Artroplastia do Ombro , Seguimentos , Humanos , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Satisfação do Paciente , Amplitude de Movimento Articular , Reoperação , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
Traditionally, surgical stabilization of the unstable shoulder has been performed through an open incision. Arthroscopic Bankart repair with suture anchors is now widely considered the treatment of choice for anterior shoulder instability in patients who have failed conservative management. Many different factors have now been elucidated for adequate treatment of glenohumeral instability. Because of technical advances in instability repair combined with an increased understanding of factors that lead to recurrent instability, the outcomes following arthroscopic Bankart repair have significantly improved and approach those of open techniques.
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Artroscopia/métodos , Instabilidade Articular/cirurgia , Articulação do Ombro/cirurgia , Artroplastia , Fibrocartilagem/cirurgia , Humanos , Cápsula Articular/cirurgia , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Lesões do Ombro , Âncoras de Sutura , Resultado do TratamentoRESUMO
INTRODUCTION: Treatment of long segment proximal humeral fractures with extension below the surgical neck into the diaphysis remains a significant challenge for orthopaedic surgeons. The purpose of this paper was to evaluate the clinical and radiological outcomes following primary long-stem RSA with cerclage fixation for complex long segment proximal humeral fractures with diaphyseal extension in patients more than 65 years old. MATERIAL AND METHODS: Between February 2010 and March 2013, 22 patients who suffered a complex proximal humerus fracture with extended diaphyseal involvement underwent surgery with long-stem RSA and cerclages fixation. There were 17 female and 5 male patients, and the mean age was 77.2 years at time of surgery (range 65-84 years). All patients had a 3 or 4-part proximal humerus fracture or a two part fracture with a split of humeral head, with extension to the proximal diaphysis. Clinical and radiographic follow-up was performed on all 22 patients at 6 weeks, at 3, 6, and 12 months postoperatively, and then at 2 years. Clinical evaluation consisted of the shoulder rating Constant scale. X ray evaluation was done to evaluate fracture healing and eventually humeral and glenoid component loosening or other complications. RESULTS: No infections were reported, neither other serious complications. Two patients developed a seroma and one patient developed chronic pain at that was treated with referral to pain management. No patients were lost at follow-up. At final follow-up, average active elevation was 132.5° (range 100°-140°), external rotation 30° (range 55°-10°). Average abduction was 120° (range 90°-135°). The mean adjusted Constant score was 72/100 (range 64-82). All fractures were healed within 3 months after surgery. No loosening of the humeral or glenoid components and no episodes of dislocation/instability were observed in this series. We did not observe scapular notching in any patient on the x-ray at most recent follow-up. CONCLUSION: Long-stem RSA with cerclages wire fixation represents a viable treatment option for complex long-segment displaced proximal humerus fractures with diaphyseal extension in patients older than 65 years. Our results suggest clinical outcomes at two years of follow up are satisfactory with an acceptable complication rate.
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Artroplastia de Substituição , Fraturas do Ombro/cirurgia , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição/métodos , Feminino , Seguimentos , Consolidação da Fratura , Humanos , Masculino , Guias de Prática Clínica como Assunto , Falha de Prótese , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/patologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Complex proximal humeral fractures are very difficult to treat particularly in patients older than 65 years with an osteoporotic bone and tuberosities compromised. The goal of this paper is to evaluate radiological outcomes at mid-term follow-up of proximal humerus fractures treated with reverse shoulder arthroplasty using a dedicated fracture stem. MATERIALS AND METHODS: The study population included 98 patients who underwent reverse shoulder with a dedicated fracture stem for an acute proximal humerus fracture; 87/98 patients were available for analysis. There were 62 female and 25 male patients, and the mean age was 76.2 years at the time of surgery (range 61-90 years). Clinical and radiological outcomes were evaluated at a mean follow-up of 27 months after surgery. RESULTS: Average active elevation was 137.7°, external rotation 29.1°, and internal rotation 40.7°. Overall, the tuberosity healing rate was 75 %. There was a significant increase in active anterior elevation, external rotation, and internal rotation among patients who demonstrated radiographic evidence of tuberosity healing. All tuberosity nonunions (21 cases) occurred preferentially in females, but this number did not reach statistical significance. CONCLUSION: RSP using a dedicated stem is a very viable solution to treat complex humerus proximal fracture. Reliable restoration of elevation can be expected. However, in patients in whom tuberosity healing occurs, a better active elevation other than restoration of active rotational movement can be observed.
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Artroplastia de Substituição/métodos , Desenho de Prótese , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese/métodos , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Percutaneous radiofrequency ablation (RFA) has been increasingly used in the treatment of osteoid osteoma (OO), as this method has provided satisfactory results with minimal morbidity. RFA traditionally has been performed by radiologists under computed tomography (CT) guidance. Advances in intraoperative imaging techniques now allow orthopedic oncologists to perform image-guided RFA in the operating room. We conducted a study to evaluate the efficacy of a novel technique that uses intraoperative CT-guided RFA to treat OO. We reviewed 28 consecutive cases of OO treated with intraoperative RFA by a single surgeon between September 2004 and December 2008. Primary or secondary success was defined as complete pain relief without evidence of recurrence after the first or second procedure, respectively. Failure was defined as the continued presence of symptoms combined with radiographic evidence of recurrence. Primary success rate was 92.8%. Two patients had a recurrence and underwent a successful second RFA. Our success rates are similar to those in the radiology literature. Further studies are needed to validate the efficacy of this novel technique.
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Ablação por Cateter , Osteoma Osteoide/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/cirurgia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To describe outcomes after surgical management of pediatric elbow dislocation with incarceration of the medial epicondyle. METHODS: We conducted a retrospective case review of 11 consecutive children and adolescents with an incarcerated medial epicondyle fracture after elbow dislocation. All patients underwent open reduction internal fixation using a similar technique. We characterized outcomes at final follow-up. RESULTS: Average follow-up was 14 months (range, 4-56 mo). All patients had clinical and radiographic signs of healing at final follow-up. There was no radiographic evidence of loss of reduction at intervals or at final follow-up. There were no cases of residual deformity or valgus instability. Average final arc of elbow motion was 4° to 140°. All patients had forearm rotation from 90° supination to 90° pronation. Average Mayo elbow score was 99.5. Four of 11 patients had ulnar nerve symptoms postoperatively and 1 required a second operation for ulnar nerve symptoms. In addition, 1 required a second operation for flexion contracture release with excision of heterotopic ossification. Three patients had ulnar nerve symptoms at final follow-up. Two of these had mild paresthesia only and 1 had both mild paresthesia and weakness. CONCLUSIONS: Our results suggest that open reduction internal fixation of incarcerated medial epicondyle fractures after elbow dislocation leads to satisfactory motion and function; however, the injury carries a high risk for complications, particularly ulnar neuropathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Luxações Articulares/cirurgia , Fraturas da Ulna/cirurgia , Adolescente , Criança , Articulação do Cotovelo/diagnóstico por imagem , Feminino , Humanos , Fraturas do Úmero/diagnóstico por imagem , Luxações Articulares/diagnóstico por imagem , Masculino , Radiografia , Resultado do Tratamento , Fraturas da Ulna/diagnóstico por imagemRESUMO
Hip dislocation secondary to developmental dysplasia of the hip is a debilitating condition. Total hip arthroplasty has proven successful in improving pain, restoring joint function, and correcting leg length discrepancies in this select population. Various techniques have been developed to address the increased complexity inherent to the reconstruction of the severely dysplastic hip. Despite this, femoral and/or sciatic nerve palsy remains a potential catastrophic complication after surgery, with reported rates up to five times that in the general population. We present three cases using a previously unreported technique for performing primary total hip arthroplasty via an anterior approach for Crowe IV hip dysplasia. The goal of this technique is to minimize the risk of postoperative nerve palsy following reconstruction of the severely dysplastic hip. A brief discussion of our technique and the topic of nerve dysfunction after total hip arthroplasty for developmental dysplasia of the hip follows.
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Artroplastia de Quadril , Luxação Congênita de Quadril/cirurgia , Adulto , Terapia Combinada , Humanos , Procedimentos Ortopédicos/métodos , Tração , Adulto JovemRESUMO
Scapulothoracic dissociation is rare, resulting from high-energy trauma to the shoulder girdle and disruption of the scapulothoracic articulation. The associated musculoskeletal, vascular, and neurologic injuries carry potentially devastating outcomes. Overall outcomes seem to be closely related to the degree of neurologic impairment sustained. However, given the wide spectrum of injury in scapulothoracic dissociation and limited data concerning outcomes, general recommendations regarding the management of this injury have been difficult to discern. This article reviews the current data regarding the evaluation, diagnosis, treatment, and outcomes after scapulothoracic dissociation.
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Escápula/lesões , Lesões do Ombro , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/terapia , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/terapia , Humanos , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/terapia , Ombro/irrigação sanguínea , Ombro/inervação , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/terapiaRESUMO
Coronal shear fractures of the femoral condyle (ie, Hoffa fracture) are an uncommon clinical entity typically seen in adults after higher-energy trauma. Historically poor outcomes have been reported in the literature with nonoperative treatment of these fractures. Conversely, open reduction and internal fixation of these fractures has been shown to produce good long-term clinical results in adults. These fractures appear to be even more uncommon in skeletally immature patients, with only 3 case reports documented in the literature to date. Two of the 3 cases presented as a symptomatic nonunion after initial nonoperative treatment. Herein we present a case report of a Hoffa fracture of the lateral femoral condyle in a 14-year-old boy after a wrestling injury. The fracture was treated with diagnostic arthroscopy followed by conversion to an arthrotomy for open reduction and internal fixation. Rigid fixation of the fracture was obtained with 4 headless compression screws. Twelve months postoperatively, the fracture was radiographically healed and the patient was pain free with restoration of full knee motion and return to sporting activity. The Hoffa fracture is a unique and relatively uncommon clinical entity that has a different personality than other intra-articular fractures of the knee in both adults and children. Instability of the fracture fragment can lead to a higher likelihood of nonunion with persistent pain and disability. These fractures should be treated with open reduction and internal fixation to achieve anatomic reduction with stable fixation and preservation of the blood supply to achieve early, active mobilization. We believe this optimizes the chance for good long-term functional results.
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Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Adolescente , Humanos , Masculino , Radiografia , Resultado do TratamentoRESUMO
Bariatric surgery dramatically alters the normal stomach anatomy resulting in a significant incidence of hiatal hernia and gastroesophageal reflux disease. Although the majority of patients remain asymptomatic, many complain of severe heartburn refractory to medical management and additional highly atypical symptoms. Here, we describe the diagnosis and treatment regarding four cases of symptomatic hiatal hernia following bariatric surgery presenting with atypical symptoms in the University Hospital, USA. Four patients presented following laparoscopic Roux-en-Y gastric bypass or duodenal switch/pancreaticobiliary bypass (DS) with disabling and intractable midepigastric abdominal pain characterized as severe and radiating to the jaw, left shoulder, and midscapular area. The pain in all cases was described as paroxysmal and not necessarily associated with eating. All four patients also experienced nausea, vomiting, and failure to thrive at various intervals following laparoscopic bariatric surgery. Routine workup failed to produce any clear mechanical cause of these symptoms. However, complimentary use of multidetector CT and upper gastrointestinal contrast studies eventually revealed the diagnosis of hiatal hernia. Exploration identified the presence of a type I hiatal hernia in all four patients, with the stomach staple lines densely adherent to the diaphragm and parietal peritoneum. Operative intervention led to immediate and complete resolution of symptoms. The presence of a hiatal hernia following bariatric surgery can present with highly atypical symptoms that do not resolve without operative intervention. Recognition of this problem should lead to the consideration of surgery in cases where patients are dependent on artificial nutritional support and whose symptoms are poorly controlled with medication alone.
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Cirurgia Bariátrica/efeitos adversos , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/cirurgia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adulto , Feminino , Hérnia Hiatal/etiologia , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Náusea e Vômito Pós-Operatórios/diagnóstico , Náusea e Vômito Pós-Operatórios/cirurgia , Reoperação , Resultado do TratamentoRESUMO
Although genetic factors are known to be important in addiction, no candidate genes have yet been consistently linked to drug use or abuse. Brain-derived neurotrophic factor (BDNF), which has been implicated in the behavioral response to psychomotor stimulants and potentiates neurotransmitters that are strongly linked to addiction, is a logical candidate gene to study. Using a drug challenge approach, we tested for association between BDNF G196A (val66met) genotype and subjective responses to amphetamine (AMPH). Healthy volunteers participated in a double blind, crossover design in which they received placebo, 10 mg, and 20 mg oral d-amphetamine in random order. Subjective and physical responses to ingestion of AMPH were measured at 30-min intervals after drug ingestion. Each subject was genotyped for the BDNF G196A polymorphism and grouped and analyzed accordingly. The effects of AMPH on ratings of arousal, energy, and heart rate were compared in subjects with the val/val genotype (N = 67) and the subjects with either the val/met or met/met genotypes (N = 32). AMPH produced less pronounced self-ratings of arousal and energy, yet higher increases in heart rate, in the val/met and met/met compared to the val/val group. These results suggest that BDNF is related to the subjective and physical response to low doses of AMPH.
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Anfetaminas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Metionina/genética , Valina/genética , Adulto , Fator Neurotrófico Derivado do Encéfalo/química , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
Previously, a missense polymorphism was identified in the mouse nicotinic receptor alpha4 subunit gene, Chrna4. This polymorphism leads to an Ala/Thr variation at amino acid position 529 of the alpha4 subunit. Chrna4 A529T is associated with several measures of acute sensitivity to nicotine as well as with mouse strain differences in nicotine-stimulated (86)Rb(+) efflux from synaptosomes. Here, we report that the variant forms of the mouse alpha4 subunit confer functional differences when expressed with the beta2 subunit in a heterologous system. alpha4beta2 receptors containing the T529 variant of the alpha4 subunit exhibited a higher EC(50) value for the high affinity receptor population and an apparent reduced sensitivity to blockade by DHbetaE relative to alpha4beta2 receptors containing the A529 variant of the alpha4 subunit. Moreover, the proportion of the total agonist-elicited current contributed by the high affinity alpha4beta2 receptor population was greater for alpha4beta2 receptors containing the alpha4(T529) variant (64%) than the alpha4beta2 receptors containing the alpha4(A529) variant (41%). These data suggest that the polymorphism in the mouse alpha4 subunit is located in a previously unidentified functional domain of the receptor subunit that influences receptor function, including regulation of the affinity population ratio of alpha4beta2 receptors.