Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loosening remains an impediment to the long-term success of total hip replacements despite numerous improvements in the materials used. In cemented prostheses, fatigue and fracture of bone cement have been implicated in the failure of these devices. A new material, self-reinforced composite poly(methyl methacrylate). (SRC-PMMA), has been developed. SRC-PMMA is formed by a novel processing method that will be described. The composite consists of high strength, highly oriented PMMA fibers embedded in a matrix of PMMA. Using a woven form of SRC-PMMA, an in vitro physical and mechanical evaluation was performed to assess the feasibility of its use in an orthopedic prosthesis. Three different weaves of SRC-PMMA were evaluated in bending and fracture toughness in air, after immersion for 30 days in 37 degrees C saline, and after gamma irradiation followed by immersion. Bending modulus and strength were decreased by gamma irradiation followed by saline immersion. The effect of saline immersion alone on bending strength and modulus was negligible. Saline immersion and gamma irradiation followed by saline immersion was shown to have little or no effect on the fracture toughness of woven SRC-PMMA. Differences in the fracture processes of the different weaves were found and can be related to the differing orientation of fibers to the fracture toughness pre-crack. Optimally incorporated SRC-PMMA absorbs the same amount of water as bone cement. Comparison to previous and current work with bone cement controls shows that SRC-PMMA is a material equal to or better than bone cement in all tests performed. It deserves further consideration as a candidate biomaterial.
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PMID:Bending and fracture toughness of woven self-reinforced composite poly(methyl methacrylate). 929 60

Total joint prostheses are often fixed in the bone using bone cement. The cement mantle, however, is prone to fatigue fracture that can lead to failure of the mantle, evolution of bone cement particles, and eventual loosening and failure of the prosthesis. A new material, self-reinforced composite poly(methyl methacrylate) (SRC-PMMA) was developed previously by the authors. This material has a similar chemical composition to bone cement, with the matrix and reinforcing fibers both fabricated from PMMA. One potential use for this material is as a precoat for hip prostheses or other stemmed prostheses. This study sought to examine the strength of the bonds that SRC-PMMA forms with simulated prostheses and bone cement. SRC-PMMA was woven about Co-Cr rods and push out tests were performed. Samples were tested in air as processed or after immersion in saline for 30 days at 37 degrees C. Three different weaves were investigated and compared to bone cement. Bone cement and SRC-PMMA formed interfacial bonds with Co-Cr rods that failed at an average load (stress) of 980 N (2.0 MPa). After saline immersion, the bone cement's interfacial bond strength was 642 N (1.23 MPa) and the tight weave SRC-PMMA was statistically stronger at 973 N (1.86 MPa). The shear strength within bone cement alone as measured by push out tests was an order of magnitude higher at 9210 N (15.2 MPa) in air and 9900 N (15.7 MPa) after saline immersion. The bond between SRC-PMMA and bone cement was 10,900 N (17.9 MPa) in air and 9610 N (15.8 MPa) after immersion in saline. Woven SRC-PMMA performed as well or better than bone cement in these push out tests.
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PMID:Interfacial properties of self-reinforced composite poly(methyl methacrylate). 961 33

A physiologically based mathematical model for skeletal muscle activated by neural impulses is presented. This model is developed specifically to capture the behavior for mammalian skeletal muscle activated by N-lets (sets of N high-frequency pulses with variable interpulse intervals). N-let pulse trains have been demonstrated as a possible means of producing contractions with reduced fatigue and fiber-type transformation, while maximizing the force-time integral per pulse (FTIpP) of electrically stimulated muscle. This model is developed by modeling the underlying biophysical processes responsible for the initiation and maintenance of force generation in muscle. The release and reaccumulation dynamics of calcium ions from the sarcoplasmic reticulum are modeled and proposed as the governing mechanism for the observed N-let effects. It is found that the new model is robust, numerically stable and easily implemented. Simulation results are presented that demonstrate the model's ability to capture a variety of the nonlinear summation, force and stiffness variation effects seen experimentally when activating skeletal muscle with N-lets. General properties of FES muscle are also predicted by the model. The significant insight provided by this model into the internal dynamics of skeletal muscle is used to assess a variety of mechanisms proposed for N-let behavior. It is postulated that the calcium release and reaccumulation dynamics, as incorporated in this model, are responsible for the N-let effects found in experiment.
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PMID:A mathematical model for skeletal muscle activated by N-let pulse trains. 974 6

The purpose of this study was to determine how chronic exertional fatigue and sleep deprivation coupled with negative energy balance affect thermoregulation during cold exposure. Eight men wearing only shorts and socks sat quietly during 4-h cold air exposure (10 degreesC) immediately after (<2 h, A) they completed 61 days of strenuous military training (energy expenditure approximately 4,150 kcal/day, energy intake approximately 3,300 kcal/day, sleep approximately 4 h/day) and again after short (48 h, SR) and long (109 days, LR) recovery. Body weight decreased 7.4 kg from before training to A, then increased 6.4 kg by SR, with an additional 6.4 kg increase by LR. Body fat averaged 12% during A and SR and increased to 21% during LR. Rectal temperature (Tre) was lower before and during cold air exposure for A than for SR and LR. Tre declined during cold exposure in A and SR but not LR. Mean weighted skin temperature (Tsk) during cold exposure was higher in A and SR than in LR. Metabolic rate increased during all cold exposures, but it was lower during A and LR than SR. The mean body temperature (0.67 Tre + 0.33 Tsk) threshold for increasing metabolism was lower during A than SR and LR. Thus chronic exertional fatigue and sleep loss, combined with underfeeding, reduced tissue insulation and blunted metabolic heat production, which compromised maintenance of body temperature. A short period of rest, sleep, and refeeding restored the thermogenic response to cold, but thermal balance in the cold remained compromised until after several weeks of recovery when tissue insulation had been restored.
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PMID:Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia. 976 Mar 7

Our objective was to compare the effect of 2 regimens for treatment of Mycobacterium avium complex (MAC) bacteraemia in an HIV-positive population on symptoms and health status outcomes using a substudy of an open-label randomized controlled trial. The study was conducted in 24 hospital-based human immunodeficiency virus (HIV) clinics in 16 Canadian cities. Patients had HIV infection and MAC bacteraemia and were given either rifampin 600 mg, ethambutol 15 mg/kg daily, clofazimine 100 mg daily and ciprofloxacin 750 mg twice daily (4-drug arm) or rifabutin 600 mg daily (amended to 300 mg daily in mid-trial), ethambutol 15 mg/kg daily and clarithromycin 1000 mg twice daily (3-drug arm). The primary health status outcome was the change on the 8-item symptom subscale of the Medical Outcome Study (MOS)-HIV Health Survey adapted for MAC. Changes on other MOS-HIV subscales and on the Karnofsky score were also evaluated. Patients on the 3-drug arm had better outcomes on the MOS-HIV symptom subscale at 16 weeks (P=0.06), with statistically significant differences restricted to night sweats and fever and chills (P < 0.001). The proportion of patients improving on the symptom subscale relative to baseline was 55% on the 3-drug arm and 40% on the 4-drug arm. Patients on the 3-drug arm also had better Karnofsky score at 16 weeks (P < 0.001) and better outcomes on the social function, mental health, energy/fatigue, health distress and cognitive function subscales of the MOS-HIV. The 3-drug arm is superior to the 4-drug arm in terms of impact on MAC-associated symptoms, functional status and other aspects of health status.
Int J STD AIDS 2000 Apr
PMID:Symptomatic and health status outcomes in the Canadian randomized MAC treatment trial (CTN010). Canadian HIV Trials Network Protocol 010 Study Group. 1077 83

This short communication is a preliminary report on a study concerning slowing down the rate of muscle fatigue when FES (Functional Electrical Stimulation) is applied for standing and walking by complete (traumatic) thoracic-level paraplegics. It is shown that randomly modulating the inter-pulse interval between FES pulses (which serve to trigger action potentials in the peripheral nerves concerned) results in a significantly lower rate of muscle fatigue, as tested in a series of leg extensions, when FES was applied at the quadriceps. Specifically, we report that the best results (longest durations of leg extension prior to onset of muscle-fatigue) were achieved with a +/- 5 msec uniformly-distributed (pseudo-) white-noise modulation at a 42 msec inter-pulse interval (24 pulses per sec). These resulted in an average increase in duration of leg extension of approximately 37% in this pilot study, as compared with unmodulated (fixed-rate) trains of FES pulses. This significant increase, even in a very preliminary study appears to merit careful further examination, since it may allow a possibly significant increase in standing duration and in walking range of paraplegics using FES for ambulation.
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PMID:Stochastically-modulated stimulation to slow down muscle fatigue at stimulated sites in paraplegics using functional electrical stimulation for leg extension. 1109 76

Exercise-induced increases in cardiac output (CO) and oxygen uptake (VO2) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function - such as calcitonin gene related peptide (CGRP) - may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 +/- 2 min to fatigue. Voluntary cycling performed both at VO2 similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33.8 +/- 3.1 pmol l(-1) (rest) to 39.5 +/- 4.3 (14%, P<0.05)) with a mean extraction over the working leg of 10% (P<0.05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33.2 +/- 3.8 to 46.9 +/- 3.6 pmol l-1, P<0.05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0.05). The exercise induced increase in leg blood flow was 10-12 fold in both spinal cord injured and controls at similar VO2 (P<0.05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 +/- 7 to 132 +/- 15 bpm) compared with controls and tetraplegics (P<0.05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.
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PMID:Leg uptake of calcitonin gene-related peptide during exercise in spinal cord injured humans. 1116 94

The aim of the study was to assess adherence with antiretroviral medication in a sample of HIV patients in Hong Kong and identify predictors of adherence. The study used a cross-sectional correlational design. Adherence behaviour was assessed with the use of self-reports. Other scales assessed knowledge with HIV medication, coping, health locus of control, anxiety, depression and fatigue. A blood sample was also obtained to assess CD4+ counts and viral load. Sociodemographic characteristics and medical information were obtained from the medical records. A high adherence rate was found in this sample of 136 predominantly Chinese patients. There were only 13.7% of the patients being classified as non-adherent. Predictors of adherence included high self-efficacy in terms of being certain that the medication schedule will be followed all or most of the time as directed, low tension-anxiety scores, and low intensity of nausea and vomiting (R2=0.304). An expanded regression model revealed additional factors influencing adherence, including coping variables, pain and numbness in the hands and feet, age, disease stage, internal locus of control, fatigue, family support and taking medication twice daily. This model explained 49% of the variance in adherence. The results suggest that adherence is a multidimensional concept. Every effort should be made to assess in individuals those variables found to affect adherence and alter them whenever possible. Continuous support of patients and individualized medication programmes that will help patients adjust their treatment to their lifestyle are recommended.
Int J STD AIDS 2002 May
PMID:Factors associated with adherence to antiretroviral medication in HIV-infected patients. 1197 33

There is an optimal load and corresponding velocity at which peak power output occurs. It is reasonable to expect that these conditions will change as a result of fatigue during 30 s of all-out cycling. This study evaluated optimal velocity after 30 s of maximal isokinetic cycle ergometer exercise and tested the hypothesis that progressive adjustment of velocity (optimized) during 30 s of all-out cycling would permit greater short-term work capacity (STWC). Non-fatigued optimal cadence [NF(OC), 109.6 (2.5) rpm] was determined for ten males on an SRM ergometer using regression analysis of the torque-angular velocity relation during a 7-s maximal acceleration. Fatigued optimal cadence [73.4 (2.4) rpm] was determined in the same way, immediately after a 30-s isokinetic test at NF(OC). A subsequent trial with cadence decreasing in steps from NF(OC) to a conservative estimate of fatigued optimal cadence [83.9 (2.8) rpm] was completed to see if more work could be done with a more optimal cadence during the test. STWC was not different ( P=0.50) between the constant [23,681 (764) J] and optimized [23,679 (708) J] conditions. Another more radical progressive change in cadence with four subjects yielded the same result (no increase in STWC). Extraneous factors apparently contribute more to variability in STWC than differences between constant and adjusted optimization of conditions.
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PMID:Fatigue and optimal conditions for short-term work capacity. 1524 93

A novel material, self-reinforced composite poly(methyl methacrylate) (SRC-PMMA) has been previously developed in this laboratory. It consists of high-strength PMMA fibers embedded in a matrix of PMMA derived from the fibers. As a composite material, uniaxial SRC-PMMA has been shown to have greatly improved flexural, tensile, fracture toughness and fatigue properties when compared to unreinforced PMMA. Previous work examined one empirically defined processing condition. This work systematically examines the effect of processing time and temperature on the thermal properties, fracture toughness and fracture morphology of SRC-PMMA produced by a hot compaction method. Differential scanning calorimetry (DSC) shows that composites containing high amounts of retained molecular orientation exhibit both endothermic and exothermic peaks which depend on processing times and temperatures. An exothermic release of energy just above Tg is related to the release of retained molecular orientation in the composites. This release of energy decreases linearly with increasing processing temperature or time for the range investigated. Fracture toughness results show a maximum fracture toughness of 3.18 MPa m1/2 for samples processed for 65 min at 128 degrees C. Optimal structure and fracture toughness are obtained in composites which have maximum interfiber bonding and minimal loss of molecular orientation. Composite fracture mechanisms are highly dependent on processing. Low processing times and temperatures result in more interfiber/matrix fracture, while higher processing times and temperatures result in higher ductility and more transfiber fracture. Excessive processing times result in brittle failure.
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PMID:The effect of processing temperature and time on the structure and fracture characteristics of self-reinforced composite poly(methyl methacrylate). 1534 21


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