RESUMO
BACKGROUND: Electronic formats of patient-reported outcome (PRO) measures are now routinely used in clinical research studies. When changing from a validated paper and pen to electronic administration it is necessary to establish their equivalence. This study reports on the value of Rasch analysis in this process. METHODS: Three groups of US pulmonary hypertension (PH) patients participated. The first completed an electronic version of the CAMPHOR Activity Limitation scale (e-sample) and this was compared with two pen and paper administrated samples (pp1 and pp2). The three databases were combined and analysed for fit to the Rasch model. Equivalence was evaluated by differential item functioning (DIF) analyses. RESULTS: The three datasets were matched randomly in terms of sample size (n = 147). Mean age (years) and percentage of male respondents were as follows: e-sample (51.7, 16.0 %); pp1 (50.0, 14.0 %); pp2 (55.5, 40.4 %). The combined dataset achieved fit to the Rasch model. Two items showed evidence of borderline DIF. Further analyses showed the inclusion of these items had little impact on Rasch estimates indicating the DIF identified was unimportant. CONCLUSIONS: Differences between the performance of the electronic and pen and paper administrations of the CAMPHOR Activity Limitation scale were minor. The results were successful in showing how the Rasch model can be used to determine the equivalence of alternative formats of PRO measures.
Assuntos
Registros Eletrônicos de Saúde , Hipertensão Pulmonar/psicologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Papel , Pacientes/psicologia , Qualidade de Vida/psicologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Benchmarking , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: We sought to examine the relationship between measures of ILD severity and PH in patients with SSc. METHODS: We identified 55 subjects from 12 PHAROS sites with RHC-proven PH and HRCT evidence of ILD. Subjects with PH due to left heart disease were excluded. Baseline HRCT scans were scored by a standardised system that graded severity of ILD. Summary statistics were generated for baseline characteristics. Spearman correlation and linear regression were used to examine relationships between ILD and PH severity variables. RESULTS: The majority of subjects were white women; nearly half had limited cutaneous SSc. Most subjects were New York Heart Association functional class II or III. Pulmonary function testing revealed moderate restriction (mean FVC 64.3 ± 17.2% predicted) with severe reduction in diffusing capacity (mean DLco 34.2 ± 13.3% predicted). RHC demonstrated mild to moderate PH (mean PAP 35 ± 9 mmHg, mean PVR 5.1 ± 3.7 WU). There was no correlation between severity of ILD (by either HRCT or PFT) and cardiac haemodynamic parameters of PH. CONCLUSIONS: No association between severity of ILD and cardiac haemodynamic profiles were identified in this cohort. We believe this underscores the complex nature of PH and ILD in individuals with SSc. We do suspect that some individuals with SSc-ILD will also have concomitant pulmonary vascular disease but simple assessments to grade severity of ILD - by PFT or HRCT estimates of ILD extent - are likely not enough to reliably distinguish between PAH versus PH-ILD. Further research into how to distinguish and manage these subsets is warranted.
Assuntos
Hipertensão Pulmonar/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Idoso , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Esclerodermia Difusa/complicações , Esclerodermia Difusa/diagnóstico por imagem , Esclerodermia Limitada/complicações , Esclerodermia Limitada/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Capacidade VitalRESUMO
BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor. PATIENTS AND METHODS: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors. PF-06939999 was administered orally once or twice a day (q.d./b.i.d.) in 28-day cycles. The objectives were to evaluate PF-06939999 safety and tolerability to identify maximum tolerated dose (MTD) and recommended part 2 dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics [changes in plasma symmetric dimethylarginine (SDMA) levels], and antitumor activities. RESULTS: In part 1 dose escalation, 28 patients received PF-06939999 (0.5 mg q.d. to 6 mg b.i.d.). Four of 24 (17%) patients reported dose-limiting toxicities: thrombocytopenia (n = 2, 6 mg b.i.d.), anemia (n = 1, 8 mg q.d.), and neutropenia (n = 1, 6 mg q.d.). PF-06939999 exposure increased with dose. Steady-state PK was achieved by day 15. Plasma SDMA was reduced at steady state (58%-88%). Modulation of plasma SDMA was dose dependent. No MTD was determined. In part 2 dose expansion, 26 patients received PF-06939999 6 mg q.d. (RP2D). Overall (part 1 + part 2), the most common grade ≥3 treatment-related adverse events included anemia (28%), thrombocytopenia/platelet count decreased (22%), fatigue (6%), and neutropenia (4%). Three patients (6.8%) had confirmed partial response (head and neck squamous cell carcinoma, n = 1; non-small-cell lung cancer, n = 2), and 19 (43.2%) had stable disease. No predictive biomarkers were identified. CONCLUSIONS: PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection.
Assuntos
Neoplasias , Proteína-Arginina N-Metiltransferases , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteína-Arginina N-Metiltransferases/genética , Idoso , Adulto , Mutação , Dose Máxima Tolerável , Fatores de Processamento de RNA , Relação Dose-Resposta a DrogaRESUMO
Pulmonary arterial hypertension (PAH) is a complex disorder in which pulmonary arterial obstruction leads to elevated pulmonary arterial resistance and right ventricular failure. Normal physiologic changes that occur during pregnancy and immediately postpartum may produce fatal consequence in PAH patients. Pregnancy in patients with PAH has a high maternal mortality, estimated at 30-56%. Contemporary estimates of mortality are better but still prohibitively high. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. Some patients, despite counselling by their physician, choose to continue with their pregnancy. In addition, some women first present with PAH during pregnancy leading to complex management issues in a high-risk patient. PAH-specific therapies may allow patients to better tolerate pregnancy. These patients should be treated by experienced physicians at tertiary care centres. This review article will focus on the management of the pregnant PAH patient and the preventative options available for this high-risk cohort.
Assuntos
Hipertensão Pulmonar/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado da Gravidez , Gravidez de Alto Risco , Aborto Terapêutico/normas , Epoprostenol/uso terapêutico , Hipertensão Pulmonar Primária Familiar , Feminino , Idade Gestacional , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/mortalidade , Piperazinas/uso terapêutico , Guias de Prática Clínica como Assunto , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/mortalidade , Purinas/uso terapêutico , Medição de Risco , Índice de Gravidade de Doença , Citrato de Sildenafila , Sulfonas/uso terapêutico , Taxa de SobrevidaRESUMO
The aim of the present study was to determine contemporary survival in pulmonary arterial hypertension (PAH), and to investigate whether or not the National Institutes of Health (NIH) equation remains an accurate predictor of survival. In 576 patients with PAH referred during 1991-2007, observed survival was described using the Kaplan-Meier method. In patients with idiopathic, familial and anorexigen-associated PAH (n = 247), observed versus NIH equation predicted survival was compared. A new survival prediction equation was developed using exponential regression analysis. The observed 1-, 3- and 5-yr survival in the total cohort were 86, 69 and 61%, respectively. In patients with idiopathic, familial and anorexigen-associated PAH, the observed 1-, 3- and 5-yr survival (92, 75 and 66%, respectively) were significantly higher than the predicted survival (65, 43 and 32%, respectively). The new equation (P(t) = e(-A(x,y,z)t), where P(t) is probability of survival, t the time interval in years, A(x,y,z) = e((-1.270-0.0148x+0.0402y-0.361z)), x the mean pulmonary artery pressure, y the mean right atrial pressure and z the cardiac index) performed well when applied to published contemporary studies of survival in PAH. Contemporary survival in the PAH cohort was better than that predicted by the NIH registry equation. The NIH equation underestimated survival in idiopathic, familial and anorexigen-associated PAH. Once prospectively validated, the new equation may be used to determine prognosis.
Assuntos
Hipertensão Pulmonar/mortalidade , Medição de Risco/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de Regressão , Testes de Função Respiratória , Análise de Sobrevida , Estados UnidosRESUMO
The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.
Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Drosophila , Interleucina-12/biossíntese , Lipoproteínas/imunologia , Macrófagos/imunologia , Glicoproteínas de Membrana/metabolismo , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Receptores de Superfície Celular/metabolismo , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/metabolismo , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Interleucina-12/genética , Lipopolissacarídeos/imunologia , Lipoproteínas/química , Lipoproteínas/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , NF-kappa B/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Regiões Promotoras Genéticas , Transdução de Sinais , Receptores Toll-Like , Transcrição Gênica , Transfecção , Células Tumorais CultivadasRESUMO
Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary hypertension (PH) is associated with vasoconstriction, thrombosis and proliferation, and the lack of endogenous prostacyclin may considerably contribute to this condition. This supports a strong rationale for prostanoid use as therapy for this disease. The first experiences of prostanoid therapy in PH patients were published in 1980. Epoprostenol, a synthetic analogue of prostacyclin, and the chemically stable analogues iloprost, beraprost and treprostinil were tested in randomised controlled trials. The biological actions are mainly mediated by activation of specific receptors of the target cells; however, new data suggest effects on additional intracellular pathways. In the USA and some European countries, intravenous infusion of epoprostenol and treprostinil, as well as subcutaneous infusion of treprostinil and inhalation of iloprost, have been approved for therapy of pulmonary arterial hypertension. Iloprost infusion and beraprost tablets have been approved in few other countries. Ongoing clinical studies investigate oral treprostinil, inhaled treprostinil and the combination of inhaled iloprost and sildenafil in pulmonary arterial hypertension. Combination of other targeted therapies with prostanoids appears to be effective and safe. After 25 yrs of continued knowledge, prostanoids remain a mainstay in the treatment of pulmonary arterial hypertension.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Prostaglandinas Sintéticas/farmacologia , Prostaglandinas Sintéticas/uso terapêutico , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vias Biossintéticas/efeitos dos fármacos , Ensaios Clínicos como Assunto , Hemodinâmica/efeitos dos fármacos , Humanos , Prostaglandinas Sintéticas/classificação , Alvéolos Pulmonares/efeitos dos fármacos , Vasodilatadores/classificaçãoRESUMO
Clearance of trebananib (AMG 386), a 64-kD antiangiogenic peptibody, has been associated with estimated glomerular filtration rate (eGFR). We prospectively evaluated trebananib pharmacokinetics and safety/tolerability in advanced solid tumor patients with varying degrees of renal function. Patients were assigned to normal renal function, mild, moderate, or severe renal dysfunction cohorts based on eGFR, received trebananib 15 mg/kg i.v. weekly, and underwent week 1 and week 5 pharmacokinetic and weekly safety assessments. For 28 patients, trebananib clearance decreased from normal renal function (1.52 mL/hr/kg), to mild (1.20 mL/hr/kg), moderate (0.79 mL/hr/kg), and severe (0.53 mL/hr/kg) renal dysfunction (P ≤ 0.001). Treatment-related adverse events showed no association with clearance. Trebananib clearance was proportional to eGFR and unrelated to pretreatment protein excretion. These data confirm a role for renal clearance of a recombinant peptibody with molecular weight <69 kD and support a longer dosing interval for patients with severe renal dysfunction.
Assuntos
Nefropatias/metabolismo , Rim/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacocinética , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Nefropatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: Treprostinil is approved for the treatment of pulmonary arterial hypertension (PAH) via continuous intravenous (IV) infusion. Treprostinil's anti-platelet aggregation characteristics and stability at room temperature may allow for low infusion rates (0.1-0.2 mL/hr) using a miniaturized infusion pump. METHODS: A 12-week, multi-center, open-label study in 12 adult PAH patients, evaluated the feasibility and safety of low-flow IV treprostinil administration via the 407C miniaturized pump. Patients receiving IV treprostinil at a stable dose were transitioned from their current CADD-Legacy pump to the 407C and were assessed for adverse events including catheter occlusions, pump alarms, and efficacy (six minute walk distance (6MWD), Borg Dyspnea Score (BDS), NYHA functional class, and PAH signs/symptoms). All patients were also maintained on therapeutic doses of warfarin, heparin or low molecular weight heparin throughout the study. RESULTS: Baseline mean (+/-SD) 6MWD was 477 +/- 76 m (n = 9) with mean BDS of 2.1 +/- 1.2 (n = 9). Week 12 mean 6MWD and BDS were 500 +/- 92 m and 2.3 +/- 1.7, respectively (n = 9). Four patients discontinued the study prematurely (3 AEs and 1 consent withdrawn). Adverse events included headache, flushing, and nausea. Pump complications occurred in 5 of 12 patients, and although no catheter occlusions occurred in any patient during the 12-week study, further study is needed regarding pump complications. CONCLUSION: This study demonstrates that treprostinil can be administered intravenously at infusion rates as low as 0.1 mL/hr for 12 weeks without catheter occlusions. Further studies are warranted because the potential for adverse events is of some concern.
Assuntos
Anti-Hipertensivos/administração & dosagem , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Bombas de Infusão , Adulto , Anti-Hipertensivos/efeitos adversos , Dispneia/fisiopatologia , Epoprostenol/administração & dosagem , Epoprostenol/efeitos adversos , Desenho de Equipamento , Tolerância ao Exercício/efeitos dos fármacos , Estudos de Viabilidade , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Bombas de Infusão/efeitos adversos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , CaminhadaRESUMO
Novel characterization of patterns of adverse events (AEs) of kinase inhibitors (KIs) could reveal new insights on human molecular physiology and methods to improve the therapeutic index of KIs. Incidence and severity of AEs for each of 157 patients enrolled in sorafenib clinical trials were determined for three clinically relevant treatment intervals: weeks 0-3, weeks 3-7, and after 7 weeks. The most common within patient co-occurrences were mucositis with dermatologic events: hand-foot syndrome (HFS; odds ratio [OR] = 4.36; p = 0.0017) and rash (OR = 5.32; p < 0.001). Prevalence of severe: alopecia (p = 0.02), diarrhea (p < 0.001), and fatigue (p = 0.005) increased over the course of therapy. Incidence of HFS (60%) and diarrhea (25%) increased up to a minimum steady-state concentration (approximately 5 mcg mL-1 ) and plateaued thereafter. Common AEs of sorafenib occur in distinct temporal and tissue distribution patterns and this analysis identified unrecognized relationships among mechanism-dependent and independent effects of a KI.
RESUMO
Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.
Assuntos
Determinação de Ponto Final , Modelos Biológicos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X , Proliferação de Células , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Humanos , Cinética , Controle de Qualidade , Carga TumoralRESUMO
During the past 10 years, the philosophy of heart failure treatment has evolved from symptom control to a combined prevention and symptom-management strategy. Recent clinical trials have proved that early detection can delay progression. Treatment of asymptomatic left ventricular dysfunction is as important as treatment of symptomatic disease. The purpose of this review is to simplify recent guidelines for pharmacological management of chronic systolic heart failure for the primary care physician and the heart failure specialist. Early recognition and prevention therapies, combined with lifestyle modification, are essential in the treatment of heart failure. Therapy with angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics is now standard. Digoxin is added to improve clinical symptoms, especially in patients with atrial fibrillation. Aldosterone antagonists may be recommended in select patients with stable New York Heart Association class III or IV heart failure. If angiotensin-converting enzyme inhibitors are not tolerated, angiotensin receptor blockers, hydralazine hydrochloride, and isosorbide dinitrate are recommended. The data on antiarrhythmic and anticoagulation therapies are inconclusive.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antiarrítmicos/uso terapêutico , Progressão da Doença , Enalapril/uso terapêutico , Humanos , Estilo de Vida , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunção Ventricular Esquerda/tratamento farmacológicoRESUMO
To selectively stain polyanionic macromolecules of growth plate cartilage and to prevent artifacts induced by aqueous fixation, proximal tibial growth plates were excised from rats, slam-frozen, and freeze-substituted in 100% methanol containing the cationic dye Alcian blue. Electron microscopic examination showed the tissue stained with Alcian blue to be comparable in ultrastructural preservation to tissues slam-frozen and freeze-substituted in the absence of Alcian blue. The extracellular matrix exhibited a characteristic staining pattern when stained by this method. The pericellular rim was identified as a band of varying width encircling the chondrocyte and its cell processes. Peripheral to the pericellular rim the heterogeneity of staining within the extracellular matrix increased, taking the form of polymorphic densities. X-ray microanalysis showed that the visual interpretation of electron density was related to the concentration of copper present, and that the concentration of sulfur was variable in the pericellular rim and in the interterritorial matrix. The difficulties associated with aqueous fixation and staining procedures are discussed in contrast to the improved preservation achieved by cryogenic methods.
Assuntos
Azul Alciano , Lâmina de Crescimento/análise , Indóis , Proteoglicanas/análise , Coloração e Rotulagem/métodos , Animais , Cobre/análise , Microanálise por Sonda Eletrônica , Matriz Extracelular/análise , Congelamento , Lâmina de Crescimento/ultraestrutura , Microscopia Eletrônica , Ratos , Ratos Endogâmicos , Enxofre/análiseRESUMO
The purpose of this study was to develop a method to prospectively quantify passive knee stability in an animal model of joint injury over time. Knee stability is defined here as the amount of translation or rotation of the tibia relative to the femur for a given application of force or moment, respectively. Five animals that had undergone transection of the anterior cruciate ligament and three control animals that had undergone a sham operation were anaesthetized and positioned in a stereotaxic frame. Motion of the tibia relative to the femur was quantified with use of reflective markers secured to modified bone pins and a three-dimensional motion analysis system. External forces and moments in the transverse plane of the tibia were measured with use of force transducers based on a strain-gauge design. Longitudinal measurements of knee stability were made before either sham surgery (control animals) or transection of the ligament (experimental animals), immediately after surgery, and at 2 and 4 months after transection. The results showed that the animals tolerated the procedures well and that systematic measurements could be obtained. The method described here has the practical advantage over cross-sectional experimental designs in that the number of subjects can be decreased while maintaining statistical power and has the further conceptual advantage that individual changes can be accounted for over time.
Assuntos
Lesões do Ligamento Cruzado Anterior , Instabilidade Articular/fisiopatologia , Traumatismos do Joelho/fisiopatologia , Articulação do Joelho/fisiopatologia , Animais , Ligamento Cruzado Anterior/fisiopatologia , Ligamento Cruzado Anterior/cirurgia , Gatos , Modelos Animais de Doenças , Desenho de Equipamento , Articulação do Joelho/cirurgia , Estudos Longitudinais , Amplitude de Movimento Articular/fisiologia , Gravação de Videoteipe , Suporte de Carga/fisiologiaRESUMO
Passive anterior-posterior displacement and medial-lateral rotation of the tibia on the femur in the feline knee were assessed before transection of the anterior cruciate ligament, immediately after transection, and 2 and 4 months after transection. Four anaesthetized experimental and three sham-operated control animals were positioned in a stereotaxic frame. Motions of the tibia relative to the femur were measured with use of 60-Hz video motion analysis, while a strain-gauged system allowed measurement of forces and moments applied to the tibia. Displacement at 15 N of anterior force and 30 degrees of knee flexion increased by an average of 6 mm following transection, and stiffness decreased by an average of 6 N/mm. At 2 and 4 months following transection, there were statistically significant reductions in this abnormal displacement. Stiffness during anterior displacement of the tibia at 30 degrees increased significantly from immediately after transection to 4 months. At 90 degrees, mean anterior displacement decreased from 5.1 mm immediately after transection to 2.9 mm at 4 months. Medial rotation at 30 degrees of knee flexion was significantly decreased from a mean of 16.5 degrees after transection to a mean of 10.7 degrees at 4 months. Changes in medial rotation at 90 degrees, lateral rotation at 90 degrees, and lateral rotation at 30 degrees were not statistically significant. These results indicate a significant change in secondary constraints to tibial motion in response to knee instability.
Assuntos
Lesões do Ligamento Cruzado Anterior , Fêmur/fisiologia , Instabilidade Articular/fisiopatologia , Articulação do Joelho/fisiologia , Amplitude de Movimento Articular/fisiologia , Tíbia/fisiologia , Animais , Ligamento Cruzado Anterior/fisiopatologia , Fenômenos Biomecânicos , Gatos , Estudos Longitudinais , Maleabilidade , Fatores de Tempo , Gravação de VideoteipeRESUMO
The relationship between the thickness of the myelin sheath and the square area of the axon was measured in both short-term and long-term remyelinated axons following demyelination in the central nervous system, and compared with that of controls. The normal linear relationship between thickness of myelin sheath and axon size was not present in either group of remyelinated axons even though there was a trend, not statistically significant, in the long-term remyelinated animals to approach that of normal animals.