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1.
Br J Sports Med ; 50(19): 1169-76, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27629403

RESUMO

The 2016 Warwick Agreement on femoroacetabular impingement (FAI) syndrome was convened to build an international, multidisciplinary consensus on the diagnosis and management of patients with FAI syndrome. 22 panel members and 1 patient from 9 countries and 5 different specialties participated in a 1-day consensus meeting on 29 June 2016. Prior to the meeting, 6 questions were agreed on, and recent relevant systematic reviews and seminal literature were circulated. Panel members gave presentations on the topics of the agreed questions at Sports Hip 2016, an open meeting held in the UK on 27-29 June. Presentations were followed by open discussion. At the 1-day consensus meeting, panel members developed statements in response to each question through open discussion; members then scored their level of agreement with each response on a scale of 0-10. Substantial agreement (range 9.5-10) was reached for each of the 6 consensus questions, and the associated terminology was agreed on. The term 'femoroacetabular impingement syndrome' was introduced to reflect the central role of patients' symptoms in the disorder. To reach a diagnosis, patients should have appropriate symptoms, positive clinical signs and imaging findings. Suitable treatments are conservative care, rehabilitation, and arthroscopic or open surgery. Current understanding of prognosis and topics for future research were discussed. The 2016 Warwick Agreement on FAI syndrome is an international multidisciplinary agreement on the diagnosis, treatment principles and key terminology relating to FAI syndrome.Author note The Warwick Agreement on femoroacetabular impingement syndrome has been endorsed by the following 25 clinical societies: American Medical Society for Sports Medicine (AMSSM), Association of Chartered Physiotherapists in Sports and Exercise Medicine (ACPSEM), Australasian College of Sports and Exercise Physicians (ACSEP), Austian Sports Physiotherapists, British Association of Sports and Exercise Medicine (BASEM), British Association of Sport Rehabilitators and Trainers (BASRaT), Canadian Academy of Sport and Exercise Medicine (CASEM), Danish Society of Sports Physical Therapy (DSSF), European College of Sports and Exercise Physicians (ECOSEP), European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA), Finnish Sports Physiotherapist Association (SUFT), German-Austrian-Swiss Society for Orthopaedic Traumatologic Sports Medicine (GOTS), International Federation of Sports Physical Therapy (IFSPT), International Society for Hip Arthroscopy (ISHA), Groupo di Interesse Specialistico dell'A.I.F.I., Norwegian Association of Sports Medicine and Physical Activity (NIMF), Norwegian Sports Physiotherapy Association (FFI), Society of Sports Therapists (SST), South African Sports Medicine Association (SASMA), Sports Medicine Australia (SMA), Sports Doctors Australia (SDrA), Sports Physiotherapy New Zealand (SPNZ), Swedish Society of Exercise and Sports Medicine (SFAIM), Swiss Society of Sports Medicine (SGMS/SGSM), Swiss Sports Physiotherapy Association (SSPA).


Assuntos
Impacto Femoroacetabular/diagnóstico , Impacto Femoroacetabular/terapia , Acetábulo/fisiopatologia , Congressos como Assunto , Consenso , Articulação do Quadril/fisiopatologia , Humanos , Sociedades
2.
Bone Joint J ; 101-B(6_Supple_B): 31-36, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146567

RESUMO

AIMS: Whether patient-reported pain differs among surgical approaches in total hip arthroplasty (THA) remains unclear. This study's purposes were to determine differences in pain based on surgical approach (direct anterior (DA) vs posterolateral (PL)) and PL approach incision length. PATIENTS AND METHODS: This was a retrospective investigation from two centres and seven surgeons (three DA, three PL, one both) of primary THAs. PL patients were categorized for incision length (6 cm to 8 cm, 8 cm to 12 cm, 12 cm to 15 cm). All patients had cementless femoral and acetabular fixation, at least one year's follow-up, and well-fixed components. Patients completed a pain-drawing questionnaire identifying the location and intensity of pain on an anatomical diagram. Power analysis indicated 800 patients in each cohort for adequate power to detect a 4% difference in pain (alpha = 0.05, beta = 0.80). RESULTS: A total of 1848 patients (982 DA, 866 PL) were included. PL patients were younger (59.4 years, sd 12.9 vs 62.7 years, sd 9.7; p < 0.001) and had shorter follow-up (3.3 years, sd 1.3 vs 3.7 years, sd 1.3; p < 0.001). DA patients reported decreased moderate to severe trochanteric (14% vs 21%; p < 0.001) and groin pain (19% vs 24%; p = 0.004) than PL patients. There were no differences in anterior, lateral, or posterior thigh, back, or buttock pain between cohorts (p = 0.05 to 0.7). PL approach incision length did not impact the incidence or severity of pain (p = 0.3 to 0.7). CONCLUSION: A significant proportion of patients perceive persistent pain following THA regardless of approach. DA patients reported less trochanteric and groin pain versus PL patients. PL incision length did not influence the incidence or severity of patient-reported pain. Cite this article: Bone Joint J 2019;101-B(6 Supple B):31-36.


Assuntos
Artroplastia de Quadril/métodos , Percepção da Dor/fisiologia , Dor Pós-Operatória/fisiopatologia , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/etiologia , Dor Musculoesquelética/fisiopatologia , Medição da Dor , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Autorrelato
3.
Bone Joint J ; 100-B(12): 1551-1558, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30499318

RESUMO

AIMS: The aims of this study were to review the surgical technique for a combined femoral head reduction osteotomy (FHRO) and periacetabular osteotomy (PAO), and to report the short-term clinical and radiological results of a combined FHRO/PAO for the treatment of selected severe femoral head deformities. PATIENTS AND METHODS: Between 2011 and 2016, six female patients were treated with a combined FHRO and PAO. The mean patient age was 13.6 years (12.6 to 15.7). Clinical data, including patient demographics and patient-reported outcome scores, were collected prospectively. Radiologicalally, hip morphology was assessed evaluating the Tönnis angle, the lateral centre to edge angle, the medial offset distance, the extrusion index, and the alpha angle. RESULTS: The mean follow-up was 3.3 years (2 to 4.6). The modified Harris Hip Score improved by 33.0 points from 53.5 preoperatively to 83.4 postoperatively (p = 0.03). The Western Ontario McMasters University Osteoarthritic Index score improved by 30 points from 62 preoperatively to 90 postoperatively (p = 0.029). All radiological parameters showed significant improvement. There were no long-term disabilities and none of the hips required early conversion to total hip arthroplasty. CONCLUSION: FHRO combined with a PAO resulted in clinical and radiological improvement at short-term follow-up, suggesting it may serve as an appropriate salvage treatment option for selected young patients with severe symptomatic hip deformities.


Assuntos
Cabeça do Fêmur/cirurgia , Luxação Congênita de Quadril/cirurgia , Articulação do Quadril/cirurgia , Osteotomia/métodos , Adolescente , Criança , Feminino , Cabeça do Fêmur/anormalidades , Cabeça do Fêmur/diagnóstico por imagem , Seguimentos , Luxação Congênita de Quadril/diagnóstico , Luxação Congênita de Quadril/fisiopatologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Humanos , Medidas de Resultados Relatados pelo Paciente , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos
4.
J Orthop Res ; 24(7): 1349-57, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16732613

RESUMO

Erosive osteolysis induced by implant-derived wear debris is mediated by recruitment and activation of osteoclasts in a pro-inflammatory microenvironment that is enriched with osteoclastogenic and pro-inflammatory cytokines such as RANKL and tumor necrosis factor alpha (TNF-alpha). These cytokines activate the transcription factor NF-kappaB and MAP kinases, including c-Jun, Erks, and p38, all known to be essential for the development of osteoclasts. We have recently documented that TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that polymethyl methacrylate (PMMA) particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of NF-kappaB and MAP kinases. More importantly, our data indicate that inhibitors of NF-kappaB and the MAP kinases p38 and ERK abrogate particle-induced osteoclastogenesis. In the current study, we investigated if inhibition of c-Jun N-Terminal kinase (JNK) pathway alters PMMA-induced osteoclastogenesis. Our findings point out that PMMA particles activate the JNK pathway in wild-type and TLR4-null (endotoxin-resistant) osteoclast precursors. This activation was selectively blocked in a dose-dependent fashion by the JNK inhibitor SP600125. Most importantly, we provide evidence that SP600125 inhibits osteoclast formation in a reversible manner. Collectively, our findings demonstrate that activation of the JNK pathway is essential for basal and PMMA-stimulated osteoclastogenesis, and buttress the potential significance of targeting the JNK pathway to inhibit osteolysis.


Assuntos
Reabsorção Óssea/etiologia , Proteínas Quinases JNK Ativadas por Mitógeno/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Polimetil Metacrilato/efeitos adversos , Animais , Antracenos , Artroplastia de Substituição/efeitos adversos , DNA/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Lipopolissacarídeos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Knockout/genética , Fosforilação , Receptor 4 Toll-Like/genética , Fator de Transcrição AP-1
5.
J Bone Joint Surg Br ; 88(10): 1279-85, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17012414

RESUMO

Arthritis of the hip in the young adult can be a disabling condition. Recent years have witnessed extensive research related to the management of this condition. This article reviews the current status with regard to aetiology, diagnosis and treatment of arthritis of the hip in the young adult.


Assuntos
Artrite/cirurgia , Articulação do Quadril/cirurgia , Acetábulo/cirurgia , Adulto , Artrite/diagnóstico por imagem , Artrite/etiologia , Artroplastia de Quadril/métodos , Artroscopia/métodos , Fêmur/cirurgia , Articulação do Quadril/diagnóstico por imagem , Humanos , Osteonecrose/complicações , Osteonecrose/cirurgia , Osteotomia/métodos , Medição da Dor , Radiografia
6.
Mol Endocrinol ; 6(12): 2153-9, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1337147

RESUMO

Collagenase is synthesized and secreted by rat osteoblastic cells in response to PTH. We have previously demonstrated that this effect involves a substantial increase in collagenase mRNA via transcription. Northern blots and nuclear run-on assays were performed to further investigate the induction of collagenase by PTH in the rat osteoblastic cell line UMR 106-01. Detectable amounts of collagenase mRNA were not apparent until 2 h of PTH treatment, showed the greatest abundance at 4 h, and declined to approximately 30% of maximum by 8 h. The changes in the rate of transcription of the collagenase gene in response to PTH paralleled and preceded the changes in the steady state mRNA levels. After an initial lag period of about 1 h, collagenase transcription rates increased from very low levels to a maximal response at 2 h, returning to about 50% of maximum by 10 h. The increased transcriptional rate of the collagenase gene was found to be dependent on the concentration of PTH, with a half-maximal response at approximately 7 x 10(-10) M rat PTH-(1-34) and a maximal effect with a dose of 10(-8) M. The PTH-mediated induction of collagenase transcriptional activity was completely abolished by cycloheximide, while transcription of the beta-actin gene was unaffected by the translation inhibitor. These data suggest that a protein factor(s) is required for PTH-mediated transcriptional induction of collagenase. Since PTH increases intracellular levels of several potential second messengers, agents that mimic these substances were employed to determine which signal transduction pathway is predominant in the PTH-mediated stimulation of collagenase transcription.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Colagenases/biossíntese , AMP Cíclico/fisiologia , Osteoblastos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Fragmentos de Peptídeos/farmacologia , Transcrição Gênica/efeitos dos fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Colagenases/genética , Ionomicina/farmacologia , Osteoblastos/metabolismo , Ratos , Proteínas Recombinantes/farmacologia , Teriparatida , Acetato de Tetradecanoilforbol/farmacologia
7.
Mol Endocrinol ; 6(11): 1834-42, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1480173

RESUMO

PTH is a potent regulator of osteoblast gene expression, yet the nuclear events that mediate PTH action are poorly understood. We were interested in identifying immediate early genes which may regulate PTH-altered gene expression in the osteoblast. Therefore, we examined the effects of PTH on c-fos and c-jun gene expression in a rat osteoblastic cell line (UMR 106-01). Under control conditions, c-fos and c-jun mRNAs were present at low basal levels. After PTH treatment, c-fos mRNA abundance dramatically increased, with a maximal and transient response at 30 min. PTH also stimulated an increase in c-jun mRNA, but in a biphasic manner, with maximal levels at 30 min and 2 h. These responses were dose dependent, not altered by cotreatment with the protein synthesis inhibitor cycloheximide, and preceded PTH-induced expression of matrix metallo-proteinase-1 mRNA. Nuclear run-on assays demonstrated an increased rate of c-fos and c-jun transcription after PTH exposure. To determine the signal transduction pathways involved, second messenger analogs were tested for their ability to mimic the effects of PTH. 8-Bromo-cAMP and phorbol 12-myristate 13-acetate (PMA) caused increases in the abundance of c-fos and c-jun transcripts. Ionomycin had no effect on the expression of these genes. Pretreatment of the cells with PMA resulted in a decrease in basal c-jun expression, but did not alter the PTH-mediated increase in c-fos, c-jun, or matrix metalloproteinase-1 mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Genes fos , Genes jun , Osteoblastos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Linhagem Celular , Colagenases/biossíntese , Colagenases/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Ionomicina/farmacologia , Metaloproteinase 1 da Matriz , Osteoblastos/metabolismo , RNA Mensageiro/biossíntese , Ratos , Sequências Reguladoras de Ácido Nucleico , Sistemas do Segundo Mensageiro , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/efeitos dos fármacos
8.
Mol Endocrinol ; 6(9): 1425-32, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1359401

RESUMO

The rat osteosarcoma cell line UMR 106-01 is a commonly used model system for the study of osteoblast function. However, it also expresses a phenotype characteristic of transformed cells. To test whether the latter could be accounted for by aberrant oncogene expression, we probed Northern blots of UMR and other osteoblastic cells with a panel of oncogene probes. These blots, when probed with a cDNA specific for v-H-ras, revealed a 7.0-kilobase (kb) H-ras-related transcript (designated HRRT) in UMR 106-01 cells that was not expressed in other osteoblastic cells. Osteoblast-enriched calvarial cells expressed the typical 1.1-kb H-ras mRNA, which was absent in UMR cells. Additionally, Western blots of lysates of UMR cells documented the presence of three proteins immunologically related to H-rasp21. To determine whether HRRT represented a recombinant retrovirus product, Northern blots were probed with a cDNA specific for the highly conserved gag-pol region of Moloney murine leukemia virus. These blots showed parallel cross-reactivity with an apparently identical transcript of 7.0 kb. The 7.0-kb transcripts detected by both v-H-ras and gag-pol probes declined to the same extent after treatment with concentrations of PTH known to inhibit proliferation of these cells. PTH regulated the abundance of HRRT in a time- and dose-dependent manner, with greatest repression of the transcript after 8 h of treatment with 10(-8) M PTH. The decrease in HRRT could not be completely accounted for by changes in transcriptional activity, as determined by nuclear run-on assays.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Neoplasias Ósseas/metabolismo , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes ras , Proteínas de Neoplasias/biossíntese , Proteína Oncogênica p21(ras)/biossíntese , Osteoblastos/efeitos dos fármacos , Osteossarcoma/metabolismo , Hormônio Paratireóideo/farmacologia , Provírus/genética , Retroviridae/genética , Animais , Northern Blotting , Neoplasias Ósseas/genética , Neoplasias Ósseas/microbiologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/genética , Proteína Oncogênica p21(ras)/genética , Osteoblastos/metabolismo , Osteossarcoma/genética , Osteossarcoma/microbiologia , Poli A/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Ratos , Crânio/citologia , Células Tumorais Cultivadas
9.
Bone Joint J ; 97-B(10): 1322-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26430005

RESUMO

We report patient-reported outcomes and complications associated with contemporary periacetabular osteotomy (PAO) surgery in treating symptomatic acetabular dysplasia and compare these outcomes with total hip arthroplasty (THA) in patients with similar demographic details. Two consecutive cohorts included patients between aged 18 to 40 years who had undergone either PAO (100 hips; 24 male, 76 female) or THA (55 hips; 18 male, 37 female). At a mean follow-up of 5.9 years (2 to 13), there was significant improvement in the modified Harris hip pain (p < 0.001, PAO and p < 0.001, THA), function (p < 0.001, PAO and p = 0.001, THA), and total scores (p < 0.001, PAO and p < 0.001, THA) within each cohort. There were no significant differences in the clinical outcome scores between the groups. Complication rates were low and similar in each cohort (p = 0.68). Similar to THA, contemporary PAO surgery is a clinically effective procedure that improves function and activity levels, provides pain relief and is associated with an acceptable complication rate.


Assuntos
Artroplastia de Quadril , Luxação do Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Osteotomia/métodos , Adolescente , Adulto , Feminino , Seguimentos , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Dor/etiologia , Complicações Pós-Operatórias , Resultado do Tratamento
10.
Bone Joint J ; 97-B(1): 29-34, 2015 01.
Artigo em Inglês | MEDLINE | ID: mdl-25568410

RESUMO

Obesity is a risk factor for complications following many orthopaedic procedures. The purpose of this study was to investigate whether obesity was an independent risk factor increasing the rate of complications following periacetabular osteotomy (PAO) and to determine whether radiographic correction after PAO was affected by obesity. We retrospectively collected demographic, clinical and radiographic data on 280 patients (231 women; 82.5% and 49 men; 17.5%) who were followed for a mean of 48 months (12 to 60) after PAO. A total of 65 patients (23.2%) were obese (body mass index (BMI) > 30 kg/m(2)). Univariate and multivariate analysis demonstrated that BMI was an independent risk factor associated with the severity of the complications. The average probability of a patient developing a major complication was 22% (95% confidence interval (CI) 11.78 to 38.21) for an obese patient compared with 3% (95% CI 1.39 to 6.58) for a non-obese patient The odds of a patient developing a major complication were 11 times higher (95% CI 4.71 to 17.60, p < 0.0001) for an obese compared with a non-obese patient. Following PAO surgery, there was no difference in radiographic correction between obese and non-obese patients. PAO procedures in obese patients correct the deformity effectively but are associated with an increased rate of complications.


Assuntos
Acetábulo/cirurgia , Índice de Massa Corporal , Obesidade/complicações , Osteotomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Acetábulo/diagnóstico por imagem , Adulto , Distribuição por Idade , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/diagnóstico , Osteotomia/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Radiografia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores de Tempo , Adulto Jovem
11.
Endocrinology ; 135(4): 1447-54, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7925106

RESUMO

Individual prostanoids have distinct potencies in activating intracellular signaling pathways and regulating gene expression in osteoblastic cells. The E-series prostaglandins (PGs) are known to stimulate matrix metalloproteinase-1 (MMP-1) synthesis and secretion in certain rodent and human osteoblastic cells, yet the intracellular events involved remain unclear. To further characterize this response and its signal transduction pathway(s), we examined prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01. Northern blot analysis demonstrated that prostaglandin E2 (PGE2) and PGE1 were very potent stimulators (40-fold) of MMP-1 transcript abundance, PGF2 alpha and prostacyclin were weak stimulators (4-fold), and thromboxane-B2 had no effect. The marked increase in MMP-1 transcript abundance after PGE2 treatment was first detected at 2 h, became maximal at 4 h, and persisted beyond 24 h. This response was dose dependent and elicited maximal and half-maximal effects with concentrations of 10(-6) and 0.6 x 10(-7) M, respectively. Cycloheximide, a protein synthesis inhibitor, completely blocked this effect of PGE2, suggesting that the expression of other genes is required. Nuclear run-on experiments demonstrated that PGE2 rapidly activates MMP-1 gene transcription, with a maximal increase at 2-4 h. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 messenger RNA (mRNA) levels, with a maximal effect quantitatively similar to that observed with PGE2. Thus, in UMR 106-01 cells, different prostanoids have distinct potencies in stimulating MMP-1 mRNA abundance. Our data suggest that PGE2 stimulation of MMP-1 synthesis is due to activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 mRNA abundance. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase-A activation.


Assuntos
Neoplasias Ósseas/química , Neoplasias Ósseas/patologia , Colagenases/genética , Osteossarcoma/química , Osteossarcoma/patologia , Prostaglandinas/farmacologia , RNA Mensageiro/análise , Tromboxano B2/farmacologia , Animais , Northern Blotting , Neoplasias Ósseas/enzimologia , Colagenases/análise , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Cicloeximida/farmacologia , Dinoprostona/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 1 da Matriz , Osteossarcoma/enzimologia , RNA Mensageiro/genética , Ratos , Fatores de Tempo , Células Tumorais Cultivadas
12.
Endocrinology ; 135(6): 2542-8, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7988442

RESUMO

The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.


Assuntos
Colagenases/genética , Osteossarcoma/metabolismo , RNA Mensageiro/metabolismo , Tretinoína/farmacologia , Animais , Northern Blotting , Colágeno/antagonistas & inibidores , Colágeno/genética , Estabilidade de Medicamentos , Indução Enzimática/fisiologia , Osteossarcoma/patologia , RNA Mensageiro/antagonistas & inibidores , Ratos , Transcrição Gênica/efeitos dos fármacos , Células Tumorais Cultivadas
13.
J Orthop Res ; 21(6): 1041-8, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14554217

RESUMO

Inflammatory osteolysis induced by implant-derived wear debris is associated with infiltration of various cell-types to the implant-bone interface leading to abundant secretion of pro-inflammatory cytokines and activation of proteinases that together lead to propagation of the localized inflammatory response and periprosthetic bone erosion. Tumor necrosis factor family members are considered to be direct mediators of inflammation and osteolysis. These cytokines exert their osteoclastic effects via activation of the transcription factor NF-kappaB and certain MAP kinases, including c-Jun, Erks and p38, all known to be essential for the development of osteoclasts. We have recently documented that the osteoclastogenic cytokines TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that PMMA particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of the transcription factor NF-kappaB. More importantly, our data indicate that inhibitors of the osteoclastogenic factors, TNF and RANKL abrogate particle-induced osteoclastogenesis. In the current study, we investigated if PMMA particles activate MAP kinases, and the potential role of these kinases as mediators of osteolysis. Using kinase assays, we show that in osteoclast precursors, PMMA particles markedly and rapidly activate p38 and ERK MAP kinases. This activation was specific, evident by complete blockade with specific inhibitory compounds. Similarly, we show that PMMA particles activate the JNK pathway, which is known to be involved in inflammatory and osteoclastogenic events. We also show that p38 MAP kinase regulates PMMA-activation of NF-kappaB, thus providing a possible mechanism for particle action in osteoclast precursors. Finally, we provide evidence that specific inhibitors of MAP kinases are capable of inhibiting PMMA-stimulated osteoclastogenesis. These data provide evidence that MAP kinases are potent mediators of particle-induced osteoclastogenesis.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/biossíntese , Osteoclastos/efeitos dos fármacos , Osteólise/induzido quimicamente , Polimetil Metacrilato/farmacologia , Animais , Células Cultivadas , Indução Enzimática , Inibidores Enzimáticos/farmacologia , MAP Quinase Quinase 4 , Masculino , Camundongos , Camundongos Endogâmicos C3H , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/biossíntese , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/biossíntese , Osteoclastos/enzimologia , Osteólise/patologia , Proteínas Quinases p38 Ativadas por Mitógeno
14.
J Bone Joint Surg Am ; 81(2): 247-55, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10073588

RESUMO

One hundred and twenty-one primary hybrid total hip replacements were performed in 107 patients. A titanium, porous-coated, hemispherical acetabular component was fixed with screws, and a collared, chromium-cobalt femoral stem, with a roughened surface and a thin layer of methylmethacrylate on the proximal third, was inserted with contemporary cementing techniques (that is, use of a femoral medullary plug, a cement gun, and centrifugation and pressurization of the cement). Fifteen patients (fifteen hips) died before a minimum duration of follow-up of seven years, four patients (four hips) were too ill for a detailed follow-up examination at the time of the study, and two patients (two hips) refused to be evaluated at the time of the latest follow-up. None of these twenty-one hips had had a revision or a reoperation at the time of the latest follow-up. Eighty-six patients (100 hips) were available for clinical follow-up at an average of 120 months (range, eighty-four to 153 months) and for radiographic follow-up at an average of 118 months (range, eighty-four to 153 months). The average age of the patients at the time of the index arthroplasty was sixty-five years (range, forty-five to eighty-seven years). Three acetabular components were revised because of dissociation of the liner in association with a fracture of a locking tine. One well fixed acetabular component was revised because of pelvic osteolysis, and the femoral stem in the same patient was revised because of aseptic loosening. None of the ninety-six remaining acetabular components migrated, was classified as radiographically loose, or was revised because of aseptic loosening. Osteolytic lesions were identified adjacent to five acetabular components, and one of them was treated with bone-grafting around the well fixed acetabular shell. Two hips had a continuous radiolucent line at the interface between the acetabular implant and the bone. Three femoral stems had evidence of radiographic debonding (a radiolucent line that was one millimeter wide or less between the cement and the prosthesis), and they were classified as radiographically loose despite excellent clinical results. Seven hips had osteolytic areas located in the proximal aspect of the most proximal zones of Gruen et al., and five had small osteolytic regions in more distal areas. The Harris hip score for the eighty-two patients (ninety-six hips) who did not have a revision improved from 48 points (range, 22 to 70 points) preoperatively to 92 points (range, 53 to 100 points) at the most recent follow-up examination. Eighty-one patients had no, slight, or mild pain in the hip, and they were satisfied with the clinical result. In the present study, the hybrid total hip replacement with use of the Harris-Galante acetabular component and the Precoat femoral stem continued to provide an excellent result for most patients at an average of approximately ten years after the operation.


Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Fêmur/cirurgia , Articulação do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos , Parafusos Ósseos , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Humanos , Artropatias/cirurgia , Masculino , Metilmetacrilato , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Índice de Gravidade de Doença , Análise de Sobrevida , Titânio
15.
J Bone Joint Surg Am ; 81(1): 66-73, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9973056

RESUMO

Two hundred and thirty-seven consecutive primary acetabular reconstructions were performed, in 213 patients, with use of a Harris-Galante porous-coated acetabular component with screw fixation between January 1984 and December 1987. Twenty-four patients (twenty-seven hips) died before a minimum duration of follow-up of eighty-four months, five patients (five hips) were too ill to return for a detailed follow-up examination at the time of the study, four patients (four hips) refused clinical and radiographic follow-up (but one of these patients had more than eighty-four months of follow-up for one side of a bilateral total hip replacement), two patients (two hips) were lost to follow-up, and two patients (two hips) refused radiographic follow-up but had adequate clinical follow-up. In addition, one patient who had had a bilateral total hip replacement had a resection arthroplasty on one side because of a late infection 115 months after the index procedure. Thus, 196 hips (83 per cent) in 177 patients were available for radiographic and clinical review after an average duration of follow-up of 122 months (range, eighty-four to 155 months). The average age of these 177 patients at the time of the operation was fifty-nine years (range, twenty-three to eighty-seven years). Eight well fixed acetabular shells (4 percent) were revised: three were revised because of dissociation of the liner in association with fractures of the tines, three were revised during revision of the femoral component, and two were revised because of retroacetabular osteolysis. In eight other hips, the acetabular liner was exchanged during revision of a loose femoral component. No acetabular component migrated, was classified as radiographically loose, or was revised because of aseptic loosening. There was no evidence of fragmentation or disruption of the titanium porous mesh of any cup. One of 528 screws broke. There were no complications associated with the insertion of the acetabular fixation screws. Osteolytic lesions were identified adjacent to nine (5 percent) of the 188 acetabular components that were in place at the time of the most recent examination. One hip, which had discontinuous osteolytic lesions in all three acetabular zones, was treated with bone-grafting around the well fixed acetabular component. Eight hips had a discontinuous radiolucent line that was 1.0 millimeter wide or less in all three zones and another two had a continuous radiolucent line that was 0.5 millimeter wide in all three zones. The average Harris hip score for the 188 hips (169 patients) that did not have revision of the acetabular shell improved from 47 points (range, 22 to 71 points) preoperatively to 89 points (range, 35 to 100 points) at the time of the latest examination. One hundred and thirty-four hips had an excellent result; twenty-six, a good result; nineteen, a fair result; and nine, a poor result. All nine hips that had a poor result were in patients who had other factors, unrelated to the acetabular component, that contributed to the low Harris hip score. In the present study, the Harris-Galante porous-coated acetabular component continued to provide excellent fixation and clinical results for most patients at an average of approximately ten years after the operation.


Assuntos
Artroplastia de Quadril , Parafusos Ósseos , Prótese de Quadril , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Materiais Revestidos Biocompatíveis , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Radiografia , Reoperação , Fatores de Tempo , Resultado do Tratamento
16.
Spine (Phila Pa 1976) ; 17(8 Suppl): S325-30, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1523520

RESUMO

Between 1981 and 1990, twenty-two patients with incomplete neurologic deficits after thoracolumbar junction fractures were treated by anterior decompression and stabilization. Two patients were unavailable for follow-up examination, eleven underwent spinal canal decompression within 48 hours of injury (Group A); and nine patients underwent surgical decompression in an average of 61 days after injury (Group B). Neurologic recovery was analyzed by a modified Frankel grading system, the ASIA motor point scale and conus medullaris function. Patients were followed for an average of 3.5 years (range, 6-92 months). No patients had any deterioration in neurologic function after surgery. Patients in Group A had a modified Frankel grade improvement with a median of two grades and a mean American Spine Injury Association motor point improvement of 21.1 +/- 4.1. Four of nine patients with conus medullaris deficits demonstrated complete functional bladder and bowel return postoperatively. Those patients in Group B had a modified Frankel grade improvement with a median of one grade and a mean ASIA motor point improvement of 7.6 +/- 1.7. None of the six patients with conus medullaris injuries showed complete improvement in bladder or bowel function postoperatively. The modified Frankel grade and ASIA motor point score improvements were significant when the two groups were compared (P less than 0.04 and P less than 0.01, respectively). In this series of patients, early anterior decompression for traumatic injuries at the thoracolumbar junction was associated with improved rates of neurologic recovery when compared to late decompression.


Assuntos
Vértebras Lombares/lesões , Doenças do Sistema Nervoso/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adolescente , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/etiologia , Complicações Pós-Operatórias , Pseudoartrose/etiologia , Radiografia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Infecções Urinárias/etiologia
17.
Bone Joint J ; 96-B(12): 1657-62, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25452369

RESUMO

The aims of this retrospective study were to compare the mid-term outcomes following revision total knee replacement (TKR) in 76 patients (81 knees) < 55 years of age with those of a matched group of primary TKRs based on age, BMI, gender and comorbid conditions. We report the activity levels, functional scores, rates of revision and complications. Compared with patients undergoing primary TKR, those undergoing revision TKR had less improvement in the mean Knee Society function scores (8.14 (-55 to +60) vs 23.3 points (-40 to +80), p < 0.001), a similar improvement in UCLA activity level (p = 0.52), and similar minor complication rates (16% vs 13%, p = 0.83) at a mean follow-up of 4.6 years (2 to 13.4). Further revision surgery was more common among revised TKRs (17% vs 5%, p = 0.02), with deep infection and instability being the most common reasons for failure. As many as one-third of patients aged < 55 years in the revision group had a complication or failure requiring further surgery. Young patients undergoing revision TKR should be counselled that they can expect somewhat less improvement and a higher risk of complications than occur after primary TKR.


Assuntos
Artroplastia do Joelho , Adulto , Fatores Etários , Feminino , Humanos , Infecções/complicações , Instabilidade Articular/complicações , Masculino , Pessoa de Meia-Idade , Atividade Motora , Complicações Pós-Operatórias , Reoperação , Estudos Retrospectivos , Falha de Tratamento
18.
Bone Joint J ; 95-B(11 Suppl A): 41-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24187350

RESUMO

Down's syndrome is associated with a number of musculoskeletal abnormalities, some of which predispose patients to early symptomatic arthritis of the hip. The purpose of the present study was to review the general and hip-specific factors potentially compromising total hip replacement (THR) in patients with Down's syndrome, as well as to summarise both the surgical techniques that may anticipate the potential adverse impact of these factors and the clinical results reported to date. A search of the literature was performed, and the findings further informed by the authors' clinical experience, as well as that of the hip replacement in Down Syndrome study group. The general factors identified include a high incidence of ligamentous laxity, as well as associated muscle hypotonia and gait abnormalities. Hip-specific factors include: a high incidence of hip dysplasia, as well as a number of other acetabular, femoral and combined femoroacetabular anatomical variations. Four studies encompassing 42 hips, which reported the clinical outcomes of THR in patients with Down's syndrome, were identified. All patients were successfully treated with standard acetabular and femoral components. The use of supplementary acetabular screw fixation to enhance component stability was frequently reported. The use of constrained liners to treat intra-operative instability occurred in eight hips. Survival rates of between 81% and 100% at a mean follow-up of 105 months (6 to 292) are encouraging. Overall, while THR in patients with Down's syndrome does present some unique challenges, the overall clinical results are good, providing these patients with reliable pain relief and good function.


Assuntos
Artroplastia de Quadril , Síndrome de Down/complicações , Síndrome de Down/fisiopatologia , Articulação do Quadril/anormalidades , Articulação do Quadril/cirurgia , Prótese de Quadril , Humanos , Fixadores Internos , Instabilidade Articular/fisiopatologia , Instabilidade Articular/cirurgia , Fatores de Risco , Taxa de Sobrevida
19.
J Thromb Haemost ; 6(10): 1655-62, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18662264

RESUMO

BACKGROUND: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common. METHODS: In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. RESULTS: The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri-operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R(2) was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R(2) of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow-up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7-11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30-0.97). CONCLUSIONS: Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non-randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene-guided warfarin dosing we created a non-profit website, http://www.WarfarinDosing.org.


Assuntos
Algoritmos , Artroplastia/métodos , Protocolos Clínicos/normas , Farmacogenética/métodos , Valor Preditivo dos Testes , Tromboembolia/prevenção & controle , Varfarina/administração & dosagem , Adulto , Idoso , Artroplastia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Medicação , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Varfarina/efeitos adversos
20.
J Arthroplasty ; 14(8): 915-7, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10614880

RESUMO

Eighty-eight primary femoral reconstructions in 80 patients were performed with the Harris-Galante uncemented femoral stem by 1 surgeon between March 1984 and December 1987. Seventy-seven femoral components in 72 patients were followed for an average 126 months or until femoral revisions. The average age at operation was 54 years (range, 30-70 years). Fifty-two patients were men, and 20 were women. The present article documents the incidence of femoral osteolysis and femoral revision in this series of this type of femoral component at an average of 10 years. Fifteen femoral components (15 of 77, 19%) were revised, 14 (14 of 77, 18%) for aseptic loosening, osteolysis, or fracture through osteolysis. The remaining 62 femoral components were functioning well (average Harris Hip Score 89 points), but 7 (11%) were loose, and 32 (52%) had femoral endosteal lysis. Overall, 19 (25%) were revised or loose, and 46 (46 of 77, 60%) had lysis. The high incidence of femoral lysis and aseptic loosening with this early design of uncemented femoral stem continues to increase at 10-year follow-up.


Assuntos
Prótese de Quadril , Falha de Prótese , Adulto , Idoso , Cimentos Ósseos , Feminino , Seguimentos , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/etiologia , Desenho de Prótese , Reoperação
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