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1.
Injury ; 55(8): 111597, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38878381

RESUMO

OBJECTIVES: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures. DESIGN: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months. There was clinical outcome data available for 105 patients at 3 months, 95 patients at 6 months and 81 patients at one year. INTERVENTION: Lateral locked plating or retrograde intramedullary nailing MAIN OUTCOME MEASUREMENTS: Radiographic alignment, functional scoring including SMFA, Bother Index, and EQ-5D. Clinical scoring of walking ability, need for ambulatory support and ability to manage stairs. RESULTS: At 3 months, there was no difference between groups (varus, neutral or valgus) with respect to any of the clinical functional outcome scores measured. At 6 months, compared to those with neutral alignment, patients with varus angulation had a worse Stair Climbing score (4.33 vs. 2.91, p = 0.05). At 12 months, the average patient with neutral or valgus alignment needed less ambulatory support than the average patient in varus. Walking distance ability was no different between the groups at any time point. With respect to the validated patient-based outcome scores, we found no statistical difference in in the SMFA, Bother, or EQ-5D between patients with valgus or varus mal-alignment and those with neutral alignment at any time point (p > 0.05). Regardless of coronal angulation, the SMFA trended towards lower (improved) scores over time, while EQ-5D scores for patients with varus angulation did not improve over time. CONCLUSIONS: Valgus angulation and neutral angulation may be better tolerated in terms of clinical outcomes like stair climbing and need for ambulatory support than varus angulation, though patient reported outcome measures like the SMFA, Bother Index and EQ-5D show no statistical significance. Most patients with distal femur fractures tend to improve during the first year after injury but many remain significantly affected at 12 months post injury.

2.
J Bone Joint Surg Br ; 92(4): 527-34, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20357329

RESUMO

It is unclear whether there is a limit to the amount of distal bone required to support fixation of supracondylar periprosthetic femoral fractures. This retrospective multicentre study evaluated lateral locked plating of periprosthetic supracondylar femoral fractures and compared the results according to extension of the fracture distal with the proximal border of the femoral prosthetic component. Between 1999 and 2008, 89 patients underwent lateral locked plating of a supracondylar periprosthetic femoral fracture, of whom 61 patients with a mean age of 72 years (42 to 96) comprising 53 women, were available after a minimum follow-up of six months or until fracture healing. Patients were grouped into those with fractures located proximally (28) and those with fractures that extended distal to the proximal border of the femoral component (33). Delayed healing and nonunion occurred respectively in five (18%) and three (11%) of more proximal fractures, and in two (6%) and five (15%) of the fractures with distal extension (p = 0.23 for delayed healing; p = 0.72 for nonunion, Fisher's exact test). Four construct failures (14%) occurred in more proximal fractures, and three (9%) in fractures with distal extension (p = 0.51). Of the two deep infections that occurred in each group, one resolved after surgical debridement and antibiotics, and one progressed to a nonunion. Extreme distal periprosthetic supracondylar fractures of the femur are not a contra-indication to lateral locked plating. These fractures can be managed with internal fixation, with predictable results, similar to those seen in more proximal fractures.


Assuntos
Placas Ósseas , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/instrumentação , Traumatismos do Joelho/cirurgia , Prótese do Joelho , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Fraturas não Consolidadas/etiologia , Humanos , Traumatismos do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Reoperação/métodos , Estudos Retrospectivos , Resultado do Tratamento
3.
J Bone Joint Surg Br ; 87(3): 374-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15773649

RESUMO

Our aim was to correlate the health status with objective and radiological outcomes in patients treated by open reduction and internal fixation for fractures of both bones of the forearm. We assessed 23 patients (24 fractures) subjectively, objectively and radiologically at a mean of 34 months (11 to 72). Subjective assessment used the disability of the arm, shoulder and hand (DASH) and musculoskeletal functional attachment (MFA) questionnaires. The range of movement of the forearm and wrist, grip and pinch strength were measured objectively and standardised radiographs were evaluated. In general, patients reported good overall function based on the DASH (mean 12; range 0 to 42) and MFA (mean 19; range 0 to 51) scores. However, pronation and grip and pinch strength were significantly decreased (p < 0.005). These deficiencies correlated with poorer subjective outcomes. Operative stabilisation of fractures of the radius and ulna led to a reliably acceptable functional outcome. However, despite these generally satisfactory results, the outcome scores worsened with reduction in the range of movement of the forearm and wrist.


Assuntos
Fraturas do Rádio/fisiopatologia , Fraturas da Ulna/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Força da Mão/fisiologia , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pronação/fisiologia , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica , Contenções , Supinação/fisiologia , Inquéritos e Questionários , Fraturas da Ulna/cirurgia
4.
J Orthop Trauma ; 15(4): 254-63, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11371790

RESUMO

OBJECTIVE: To observe and report the clinical results of indirect plating techniques in the treatment of femoral shaft nonunions originally treated with intramedullary nailing. DESIGN: Prospective consecutive. SETTING: Regional trauma center. PATIENTS: A consecutive series of twenty-three patients with nonunion of femoral shaft fractures previously treated with intramedullary nailing. INTERVENTION: Surgical treatment with indirect plating techniques using the AO 95-degree condylar blade plate in nonunions of the distal and proximal one thirds and broad large-fragment dynamic compression plating in nonunions of the middle one third, with selective autologous cancellous bone grafting. Emphasis was placed on preoperative planning, intraoperative attention to soft tissue sparing and selection of the appropriately applied implant to correct deformity and obtain union. MAIN OUTCOME MEASUREMENTS: Healing rate and time, operative blood loss and time, and incidence of complications, including hardware failure, loss of fixation, infection, and postoperative malalignment. RESULTS: Twenty-one of the twenty-three nonunions healed without further intervention at an average of twelve weeks (range 10 to 16 weeks) postoperatively. The two remaining patients (9 percent) had early breakage of their hardware, requiring repeat plating. Union in both of these cases occurred within sixteen weeks of the revision (12 and 16 weeks). Including the two patients requiring reoperation, all twenty-three nonunions healed at an average of seventeen weeks (range 10 to 24 weeks) from the initial plating procedure. There were no intraoperative complications. Average operative time was 164 minutes (range 120 to 240 minutes), and blood loss was 340 milliliters (range 200 to 700 milliliters). There were no cases of significant postoperative axial or rotational malalignment (more than 5 degrees), limb length discrepancy (more than 1 centimeter), or deep infections. CONCLUSIONS: Modern plating techniques are effective in the treatment of femoral shaft nonunions after intramedullary fracture fixation. The authors consider this method particularly valuable in the presence of deformity. Union occurred reliably with few complications.


Assuntos
Fraturas do Fêmur/cirurgia , Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Fraturas não Consolidadas/cirurgia , Adulto , Idoso , Pinos Ortopédicos , Placas Ósseas , Transplante Ósseo , Diáfises/cirurgia , Desenho de Equipamento , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fixação Intramedular de Fraturas/instrumentação , Consolidação da Fratura/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Resultado do Tratamento
5.
J Orthop Trauma ; 15(4): 264-70, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11371791

RESUMO

OBJECTIVES: To describe the technique and results of using blocking screws and intramedullary nails to treat patients with fractures of the proximal third of the tibial shaft. DESIGN: Prospective. SETTING: Level I trauma centers. PATIENTS: Twelve consecutive patients treated with intramedullary nailing and blocking screws for fractures of the proximal third of the tibial shaft. INTERVENTION: Patients were treated with intramedullary nails and blocking screws. MAIN OUTCOME MEASURE: The alignment of fractures was determined using standard anteroposterior and lateral radiographs after surgery and at each follow-up examination. One patient was lost to follow-up. All other patients were followed at regular intervals until union or establishment of a nonunion. Changes in alignment and complications were noted. RESULTS: Postoperatively, all patients had less than 5 degrees of angular deformity in the planes in which blocking screws were used to control alignment. One patient had postoperative malalignment (6 degrees of valgus), but a lateral blocking screw to control valgus deformity was not used in this patient. One patient was lost to follow-up. Eleven patients were followed up to union (n = 10) or establishment of a nonunion (n = 1). Ten of eleven patients maintained their postoperative fracture alignment at their last follow-up examination (average follow-up of thirty-three weeks). One patient progressed from 6 degrees of valgus immediately after surgery to 10 degrees of valgus at union. This patient did not have a blocking screw to control valgus angulation. CONCLUSIONS: Blocking screws are effective to help obtain and maintain alignment of fractures of the proximal third of the tibial shaft treated with intramedullary nails.


Assuntos
Pinos Ortopédicos , Parafusos Ósseos , Fixação Intramedular de Fraturas/métodos , Tíbia/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mau Alinhamento Ósseo/diagnóstico por imagem , Mau Alinhamento Ósseo/etiologia , Feminino , Seguimentos , Fixação Intramedular de Fraturas/instrumentação , Consolidação da Fratura , Fraturas não Consolidadas , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Fraturas da Tíbia/diagnóstico por imagem
6.
J Orthop Trauma ; 15(3): 161-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11265005

RESUMO

OBJECTIVES: To compare union rates and complications of retrograde intramedullary nailing of femoral shaft fractures with those of antegrade intramedullary nailing. DESIGN: Retrospective. SETTING: Level I trauma center. PATIENTS: Two hundred eighty-three consecutive adult patients with 293 fractures of the femoral shaft who underwent stabilization with antegrade or retrograde inserted femoral nails were studied. There were 140 retrograde nails and 153 antegrade nails. Twelve fractures in twelve patients were excluded (three in patients who died early in the postoperative period, three in patients because of early amputation, four in patients who were paraplegic, and two in patients who fractured through abnormal bone owing to metastatic carcinoma), leaving 134 fractures treated with retrograde nails and 147 treated with antegrade nails. One hundred four femurs treated with retrograde nails (Group R) and ninety-four femurs treated with antegrade nails (Group A) had sufficient follow-up and served as the two study groups. The average clinical follow-up was twenty-three months (range 6 to 66 months) for Group R and twenty-three months (range 5 to 64 months) for Group A. Both groups were comparable with regard to age, gender, number of open fractures, degree of comminution, mode of interlocking (i.e., static or dynamic), and nail diameter (p > 0.05). INTERVENTION: Retrograde intramedullary nails were inserted through the intercondylar notch of the knee, and antegrade nails were inserted through the pirformis fossa using standard techniques. MAIN OUTCOME MEASURES: Union, delayed union, nonunion, malunion, and complication rates. RESULTS: After the index procedure there were no significant differences in healing or incidence of malunion between Group R and Group A (p > 0.05). Healing after the index procedure occurred in ninety-one (88 percent) of the femurs in Group R and in eighty-four (89 percent) of the femurs in Group A. In Group R, there were seven delayed unions (7 percent) and six nonunions (6 percent). In Group A, there were four delayed unions (4 percent) and six nonunions (6 percent). Healing ultimately occurred in 100 (96 percent) femurs from Group R and in ninety-three (99 percent) femurs from Group A. In Group R, there were eleven malunions (11 percent), and in Group A, there were twelve malunions (13 percent). When patients with ipsilateral knee injuries were excluded, the incidence of knee pain was significantly greater for Group R patients (36 percent) than for Group A patients (9 percent) (p < 0.001). When patients with ipsilateral hip injuries were excluded, the incidence of hip pain was significantly greater for Group A patients (10 percent) than for Group R patients (4 percent) (p < 0.05). CONCLUSIONS: Retrograde and antegrade nailing techniques provided similar results in union and malunion rates. There were more complications related to the knee after retrograde nailing and more complications related to the hip after antegrade nailing.


Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Seguimentos , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura/fisiologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Probabilidade , Radiografia , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
7.
J Orthop Trauma ; 15(2): 90-5, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11232660

RESUMO

OBJECTIVES: To determine factors associated with angular malalignment of femoral shaft fractures treated with intramedullary nails and to determine differences in the incidence of angular malalignment based on fracture location, fracture comminution, and method of treatment (i.e., antegrade or retrograde). DESIGN: Retrospective. SETTING: Level I trauma center. PATIENTS: Three hundred sixty patients with 374 femoral shaft fractures were identified from a prospectively obtained orthopaedic trauma database. Complete sets of immediate postoperative anteroposterior and lateral radiographs were available for 355 (95 percent) of the 374 fractures. INTERVENTION: Patients were treated with antegrade (183 cases) or retrograde (174 cases) intramedullary femoral nailing. MAIN OUTCOME MEASURE: Goniometric measurements were made on all immediate postoperative radiographs to determine the coronal plane and sagittal plane angular alignments. A multiple linear regression statistical analysis was used to determine factors associated with increasing angular malalignment. The incidence of malalignment was determined using more than 5 degrees of deformity in any plane as the definition of malalignment. RESULTS: Proximal fracture location, distal fracture location, and unstable fracture pattern were associated with increasing fracture angulation (p < 0.001). Fracture location in the middle third, stable fracture pattern, method of treatment (i.e., antegrade or retrograde), and nail diameter were not associated with increasing fracture angulation (p > 0.05). The incidence of malalignment was 9 percent for the entire group of patients, 30 percent when the fracture was of the proximal third of the femoral shaft, 2 percent when the fracture was of the middle third, and 10 percent when the fracture was of the distal third. The incidence of malreduction was 7 percent for patients with stable fracture patterns and 12 percent for those with unstable fracture patterns. CONCLUSIONS: Patients with fractures of the proximal third of the femoral shaft treated with intramedullary nails are at highest risk for malalignment. Proximal fracture location, distal fracture location, and unstable fracture pattern are associated with increasing fracture angulation.


Assuntos
Mau Alinhamento Ósseo/etiologia , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Mau Alinhamento Ósseo/diagnóstico , Mau Alinhamento Ósseo/epidemiologia , Pinos Ortopédicos , Criança , Feminino , Fraturas do Fêmur/diagnóstico , Fixação Intramedular de Fraturas/métodos , Humanos , Incidência , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo
8.
J Orthop Trauma ; 14(7): 475-82, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11083609

RESUMO

OBJECTIVE: To observe the results and describe the technique of closed reduction and placement of a two-pin supra-acetabular external fixator, followed by immediate weight bearing, in the treatment of displaced vertically stable lateral compression pelvic fractures. DESIGN: Prospective, consecutive SETTING: Regional trauma center PATIENTS: A consecutive series of fourteen patients with displaced, vertically stable lateral compression pelvic fractures who were transported to a regional trauma center. INTERVENTION: Surgical treatment with closed reduction and maintenance of the distraction force with a two-pin, single-bar, supra-acetabular external fixator, followed by immediate weight bearing. MAIN OUTCOME MEASUREMENTS: Healing rate and time, operative blood loss and time, quality of reduction, time to full weight-bearing, and incidence of complications, including neurovascular deficits, loss of reduction, nonunion, pin tract infections, and chronic pain. RESULTS: A symmetric reduction of both hemipelves was achieved in all fourteen patients. Time to healing averaged 8.2 weeks (seven to twelve weeks), and no fixator required removal before healing. There were no delayed unions or nonunions, and none of the fractures displaced significantly after initial reduction. Average surgical time was thirty-seven minutes (range, twenty-five to sixty minutes) with an estimated blood loss of less than fifty milliliters. Patients were allowed to bear full weight immediately and were able to do so without ambulatory assistive devices within an average of twelve days (range, three to eighteen days). Complications consisted of three minor pin tract infections, one temporary lateral femoral cutaneous nerve palsy, one late pin tract abscess, and one patient with chronic low-back pain. CONCLUSIONS: Treatment of type B lateral compression injuries of the pelvic ring with anterior distraction external fixation is a highly effective yet relatively simple and minimally invasive treatment method. Surgical time and blood loss are minimal, and patients can be effectively and rapidly mobilized. Based on our experience, we believe this method to be a valuable tool in the treatment of these fractures.


Assuntos
Fixadores Externos , Fraturas Ósseas/cirurgia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Adolescente , Adulto , Deambulação Precoce , Feminino , Fraturas Ósseas/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/cirurgia , Estudos Prospectivos , Radiografia , Resultado do Tratamento
9.
Clin Orthop Relat Res ; (375): 30-42, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10853151

RESUMO

The goal of the current study was to analyze patients treated with the Gamma nail, and to describe techniques that prevent commonly reported complications. One hundred patients with closed peritrochanteric femur fractures were treated by one surgeon using the Gamma nail. Ninety patients met the minimum 6 month followup requirement. Eighty-eight of the 90 fractures (98%) healed after the index procedure. There were nine (10%) complications (nine patients) with four patients (4%) requiring surgical intervention. One patient required total hip arthroplasty because of nonunion, and one patient required cerclage wiring of a postoperative femoral fracture. The third patient had an infection develop which resolved after debridement and a course of antibiotics. The fourth patient complained of thigh pain, which resulted in hardware removal. In the five remaining patients with complications, one patient had multi-infarct dementia and the family refused additional treatment, two patients with intraoperative femur fractures did not require treatment and two patients with thigh pain did not require additional treatment. Surgical time averaged 53 minutes and blood loss averaged 104 cc. Percutaneous fixation using the Gamma nail is effective in treating patients with peritrochanteric fractures. Surgical time and blood loss were minimized, early weightbearing was initiated, and previously reported complications were decreased.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas , Fraturas do Quadril/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fixação Intramedular de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
10.
J Arthroplasty ; 15(2): 146-52, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10708077

RESUMO

The results of 123 total hip replacements with a noncemented Harris-Galante I acetabular component were reviewed (minimum 5-year clinical follow-up). The average clinical follow-up was 7 years (range, 5-10.8 years). No acetabular components were revised for loosening. One cup was revised for recurrent dislocation. In 3 cases, the acetabular liner was replaced at the time of femoral component revision (aseptic loosening), and in 1 case, a liner was revised because of recurrent dislocations. Of the hips, 92 had a complete set of radiographs for analysis. None of the acetabular components had migrated. Of the 92 acetabular components, 90 were considered radiographically stable (98%). Of these hips, 24 had linear radiolucencies of < or =2 mm in < or =2 of 4 zones and were considered stable. Two cups (2%) were considered possibly unstable. One of these had a linear radiolucent line in 3 zones, and the other had an osteolytic lesion measuring 6 x 11 mm in greatest dimensions. No acetabular components were definitely unstable. The average Harris Hip Score improved from 50 points (range, 17-89 points) preoperatively to 95 points (range, 74-99 points) at the latest follow-up examination. The average Hospital for Special Surgery hip score improved from 21 points (range, 10-31 points) preoperatively to 38 points (range, 27-40) at the last follow-up examination. Noncemented acetabular fixation with the Harris-Galante I component showed excellent clinical results at a minimum of 5 years' follow-up.


Assuntos
Artroplastia de Quadril , Artroplastia de Quadril/métodos , Parafusos Ósseos , Cimentação , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Radiografia , Reoperação , Fatores de Tempo
11.
J Orthop Trauma ; 14(1): 10-4, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10630796

RESUMO

OBJECTIVE: To evaluate healing rates of femoral shaft fractures treated with interlocked nails inserted without reaming. STUDY DESIGN: Review of prospectively collected data. SETTING: Level I trauma center. METHODS: From the trauma registry, 159 patients with 164 femoral shaft fractures were identified who had been treated from March 1993 through December 1995 with femoral nails inserted without reaming in either an antergrade or retrograde manner. Fractures were classified according to the AO/OTA method. Patients were followed for a minimum of one year with clinical and radiographic examinations. RESULTS: One hundred twenty-one patients with 125 fractures were available for review. Average follow-up was 18.3 months (range 12 to 59 months). One hundred sixteen of the 125 fractures (93 percent) healed after the index procedure. Type A fractures healed at an average of 3.8 months (range 2 to 8 months), Type B fractures at 4.8 months (range 2 to 16 months), and Type C fractures at 6.2 months (range 3 to 12 months). There were no increases in complication rates or differences in ranges of knee and hip motion as compared with other published series. Overall, there was no difference in the length of time to union between antegrade or retrograde nailings, and the healing rates for the two methods showed only a small statistical difference. CONCLUSIONS: The use of femoral nails inserted in an unreamed manner in this series produced healing rates comparable with historic standards using reamed insertion. Smaller diameter nails inserted without reaming did not compromise fracture management and produced no increase in complication rates. The causes for delayed union or nonunion appear to be multifactorial, and secondary procedures should be considered if fractures have demonstrated little or no healing by three months.


Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Consolidação da Fratura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fraturas do Fêmur/classificação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Surg Oncol ; 5(5-6): 221-9, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9129134

RESUMO

Specific active immunization with tumour cells and IL-1beta or IL-2 was examined in a murine model. Mice were treated with irradiated B16 melanoma, IL-1beta or IL-2 only, or with B16 plus cytokines prior to i.v. challenge with viable B16. Lung metastases were recorded after 28 days. Treatment with cytokine alone was not protective. Treatment with B16 alone afforded moderate protection. Treatment with B16 in combination with either cytokine resulted in a significant level of B16 specific protection which was dependent on the dose of cytokine used. Multiple immunizations with B16 provided limited protection which was significantly improved with IL-2. Immunization with B16 in combination with both cytokines at doses that alone failed to enhance immunity resulted in significant protection, suggesting that the two cytokines act at least additively. These studies demonstrate the significant benefit of specific active immunization with tumour cells in combination with low doses of IL-1beta or IL2.


Assuntos
Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Lewis/terapia , Imunoterapia , Interleucina-1/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Pulmonares/terapia , Melanoma Experimental/terapia , Neoplasias Cutâneas/terapia , Análise de Variância , Animais , Carcinoma Pulmonar de Lewis/imunologia , Modelos Animais de Doenças , Feminino , Interleucina-1/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Pulmonares/imunologia , Melanoma Experimental/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Cutâneas/imunologia , Taxa de Sobrevida , Resultado do Tratamento , Vacinação/métodos
13.
Ann Surg ; 219(2): 120-30, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8129482

RESUMO

OBJECTIVE: The purpose of this study was to evaluate a large number of patients with cutaneous melanoma who had or who were at risk for lymph node metastases to contribute to the understanding of the behavior of and appropriate management of draining nodes. A major goal of the study was to reassess the clinical impact of elective lymph node dissections (ELND) in a large patient population. SUMMARY BACKGROUND DATA: Large retrospective studies suggest that ELND may improve the prognosis of patients with intermediate thickness melanomas; however, that improvement has not been observed in two randomized prospective controlled trials. METHODS: The charts of 4682 patients treated at a single institution for localized or regional disease were reviewed individually. The median follow-up was 4.7 years, with 814 patients followed more than 10 years. The data were tabulated and evaluated with the aid of a computer data base system. RESULTS: Among patients with nodal metastases, 10% of nodal metastases were to contralateral nodes, and 6% were to nodal basins that would not be predicted by classic models of lymphatic drainage; in 13% of patients, nodal metastases occurred to greater than one nodal basin (3% of the entire study group). For all thickness ranges, the incidence of nodal metastases was comparable to the incidence of distant metastases; intermediate-thickness lesions had no relative predilection for nodal metastases. At the initial evaluation, regional nodal basins were clinically negative in 3550 patients, of whom 911 (25.7%) underwent ELND. Stratified into five thickness groups (< 0.76 mm, 0.76 to 1.5 mm, 1.5 to 2.5 mm, 2.5 to 4 mm, and > 4 mm), pathologically positive nodes were identified in 0%, 5%, 16%, 24%, and 36%, respectively (16% overall). Among the 911 patients who underwent ELND, 214 (23%) had nodal metastases, 143 at the time of ELND and 71 at a later date. Of these 71 patients, 31 (44%) had nodal metastases in a previously dissected nodal basin, and 40 (56%) had them in basins not previously dissected. The survival of patients with clinically negative nodes treated with and without ELND were compared. The two groups were well matched for major prognostic factors. Stratified by Breslow thickness and primary site, no significant improvement in survival was observed with ELND. CONCLUSIONS: Because of the significant incidence of metastases to contralateral and atypical nodal basins, lymphoscintigraphy may be justified for the preoperative evaluation of patients for ELND. However, the therapeutic value of ELND is questionable as a result of (1) the finding that the risk of nodal metastases is not relatively more common than is that of distant metastases among patients with intermediate-thickness melanomas, (2) the fact that only 16% of ELND were positive, (3) the finding that ELND may not prevent recurrent nodal disease in the dissected basin, and (4) the absence of any apparent impact on survival among patients who underwent ELND.


Assuntos
Excisão de Linfonodo , Melanoma/secundário , Neoplasias Cutâneas/patologia , Feminino , Seguimentos , Humanos , Incidência , Metástase Linfática , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Fatores de Risco , Análise de Sobrevida
14.
Nucleic Acids Res ; 17(14): 5633-50, 1989 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-2762151

RESUMO

The rat tropomyosin 1 gene gives rise to two mRNAs encoding rat fibroblast TM-1 and skeletal muscle beta-tropomyosin via an alternative splicing mechanism. The gene is comprised of 11 exons. Exons 1 through 5 and exons 8 and 9 are common to all mRNAs expressed from this gene. Exons 6 and 11 are used in fibroblasts as well as smooth muscle whereas exons 7 and 10 are used exclusively in skeletal muscle. In the present studies we have focused on the mutually exclusive internal alternative splice choice involving exon 6 (fibroblast-type splice) and exon 7 (skeletal muscle-type splice). To study the mechanism and regulation of alternative splice site selection we have characterized the branch points used in processing of the tropomyosin pre-mRNAs in vitro using nuclear extracts obtained from HeLa cells. Splicing of exon 5 to exon 6 (fibroblast-type splice) involves the use of three branch points located 25, 29, and 36 nucleotides upstream of the 3' splice site of exon 6. Splicing of exon 6 (fibroblast-type splice) or exon 7 (skeletal muscle type-splice) to exon 8 involves the use of the same branch point located 24 nucleotides upstream of this shared 3' splice site. In contrast, the splicing of exon 5 to exon 7 (skeletal muscle-type splice) involves the use of three branch sites located 144, 147 and 153 nucleotides, upstream of the 3' splice site of exon 7. In addition, the pyrimidine content of the region between these unusual branch points and the 3' splice site of exon 7 was found to be greater than 80%. These studies raise the possibility that the use of branch points located a long distance from a 3' splice site may be an essential feature of some alternatively spliced exons. The possible significance of these unusual branch points as well as a role for the polypyrimidine stretch in intron 6 in splice site selection are discussed.


Assuntos
Genes , Precursores de RNA/genética , Splicing de RNA , Tropomiosina/genética , Animais , Sequência de Bases , Éxons , Fibroblastos/metabolismo , Íntrons , Dados de Sequência Molecular , Músculos/metabolismo , Plasmídeos , Ratos , Moldes Genéticos , Transcrição Gênica
15.
Genes Dev ; 2(12A): 1627-38, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3215513

RESUMO

A single rat gene encodes both fibroblast TM-1 and skeletal muscle beta-tropomyosin by an alternative RNA-processing mechanism. The gene contains 11 exons: Exons 1-5 and exons 8 and 9 are constitutive exons common to all mRNAs expressed from this gene; exons 6 and 11 are used in fibroblasts as well as smooth muscle; exons 7 and 10 are used exclusively in skeletal muscle. We have studied the internal alternative RNA splice choice (exons 6 and 7) of the rat tropomyosin 1 gene in vitro, using nuclear extracts obtained from HeLa cells. Use of alternative splice sites in vitro is dependent on the ionic conditions of the assay, and correct splicing occurs only under well-defined salt conditions. Splicing of exon 5 to exon 6 (fibroblast-type splice) and exon 5 to exon 7 (skeletal muscle-type splice) was dependent on precursors in which exon 6 or 7 was first joined to exon 8. The same patterns of alternatively spliced RNAs were formed when similar templates were introduced in HeLa cells by transfection. Thus, there appears to be an ordered pathway of splicing in which the internal alternatively spliced exons must first be joined to the downstream constitutive exon before they can be spliced to the upstream constitutive exon. The data are consistent with a model in which the critical event in alternative splicing occurs during the joining of exon 6 to exon 8 (fibroblast-type splice) or exon 7 to exon 8 (skeletal muscle-type splice).


Assuntos
Precursores de RNA/metabolismo , Splicing de RNA , RNA Mensageiro/biossíntese , Tropomiosina/biossíntese , Animais , Extratos Celulares , Éxons , Humanos , Íntrons , Magnésio/farmacologia , Cloreto de Magnésio , Modelos Genéticos , Plasmídeos , Cloreto de Potássio/farmacologia , Precursores de RNA/genética , RNA Mensageiro/genética , Ratos , Transfecção , Tropomiosina/genética
16.
J Biol Chem ; 259(22): 14136-43, 1984 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-6548747

RESUMO

We have constructed a cDNA-expression library of approximately 100,000 members from embryonic chicken smooth-muscle mRNA using the plasmid-expression vectors pUC8 and pUC9. Using an immunological screening procedure and 32P-labeled cDNA probes, we have identified and isolated clones encoding smooth-muscle tropomyosin. Plasmid pSMT-10 (approximately 1100 base pairs) was found to hybrid-select mRNA for smooth-muscle alpha-tropomyosin. DNA-sequence analysis revealed that pSMT-10 contained the entire coding region for alpha-tropomyosin and portions of the 5'- and 3'-untranslated regions. Comparison of the derived amino acid sequence of smooth-muscle alpha-tropomyosin with known skeletal-muscle (rabbit and chicken) and platelet (equine) sequences revealed extensive homology between the various proteins. The smooth-muscle tropomyosin shows the greatest sequence divergence from the skeletal-muscle tropomyosins at the COOH-terminal region. In contrast, the smooth-muscle tropomyosin is most homologous to the platelet tropomyosin at the COOH-terminal end. The relationship of the various tropomyosin sequences to function (e.g. interactions with troponin) are considered.


Assuntos
Clonagem Molecular , DNA/análise , Músculo Liso/análise , Tropomiosina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Galinhas , Peso Molecular , Plasmídeos , RNA Mensageiro/metabolismo
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