A post mortem study of equine digital flexor tendons

The results of a survey are presented in which 589 limbs from 206 horses were dissected. In174 of the limbs lesions were found in either the superficial (131) or deep (43) digital flexor tendons. Changes occurring with age were also recorded. The sites of the abnormalities and their macroscopical appearance are described and the value of the results is considered in relation to the diagnosis and the treatment of clinical lesions.     

Factors affecting the ultrasonic properties of equine digital flexor tendons

Dietary treatment with three diets differing in vitamin E, Low E (15 mg of vitamin E/kg diet), Medium E (150 mg/kg), or High E (1,500 mg/kg), resulted in guinea pigs with low (but nondeficient), intermediate, or high heart alpha-tocopherol concentration. Neither the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reductase, nor the nonenzymatic antioxidants, GSH, ascorbate, and uric acid were homeostatically depressed by increases in heart alpha-tocopherol. Protection from both enzymatic (NADPH dependent) and nonenzymatic (ascorbate-Fe2+) lipid peroxidation was strongly increased by vitamin E supplementation from Low to Medium E whereas no additional gain was obtained from the Medium E to the High E group. The GSH/GSSG and GSH/total glutathione ratios increased as a function of the vitamin E dietary concentration closely resembling the shape of the dependence of heart alpha-tocopherol on dietary vitamin E. The results show the capacity of dietary vitamin E to increase the global antioxidant capacity of the heart and to improve the heart redox status in both the lipid and water-soluble compartments. This capacity occurred at levels six times higher than the minimum daily requirement of vitamin E, even in the presence of optimum dietary vitamin C concentrations and basal unstressed conditions. The need for vitamin E dietary supplementation seems specially important in this tissue due to the low constitutive levels of endogenous enzymatic and nonenzymatic antioxidants present of the mammalian heart in comparison with those of other internal organs.     

Ultrasonographically detected changes in equine superficial digital flexor tendons during the first months of race training

The forelimb superficial digital flexor (SDF) tendons of 6 Thoroughbreds were examined clinically and ultrasonographically during the first 4 months of race training. Sonograms were interpreted clinically and by use of computer-aided analysis. Tendon tissue from all horses was examined histologically at the end of the study. Computer-aided analysis of sonograms of the SDF tendons revealed trends toward an increase in mean cross-sectional area and a decrease in mean echogenicity over time with training. An inverse relation was found between increase in cross-sectional area and decrease in mean echogenicity over time in training. Two of the trained horses developed clinical signs of mild SDF tendonitis. Ultrasonography revealed an increase in cross-sectional area and decrease in mean echogenicity of clinically affected areas of the SDF tendons of 1 horse, compared with changes observed prior to the onset of tendonitis (these changes were not statistically significant). Blood vessels and lymphatics supplying the clinically and ultrasonographically affected tendon sites were large and thick-walled. These changes were not observed in the tendons of the other horses at the end of the study. The authors conclude that equine SDF tendons adapt to the early months of race training by increasing in size and decreasing in echogenicity, as determined by ultrasonography.     

A new method to estimate parameters of linear compartmental models using artificial neural networks

At present, the preferred tool for parameter estimation in compartmental analysis is an iterative procedure; weighted nonlinear regression. For a large number of applications, observed data can be fitted to sums of exponentials whose parameters are directly related to the rate constants/coefficients of the compartmental models. Since weighted nonlinear regression often has to be repeated for many different data sets, the process of fitting data from compartmental systems can be very time consuming. Furthermore the minimization routine often converges to a local (as opposed to global) minimum. In this paper, we examine the possibility of using artificial neural networks instead of weighted nonlinear regression in order to estimate model parameters. We train simple feed-forward neural networks to produce as outputs the parameter values of a given model when kinetic data are fed to the networks' input layer. The artificial neural networks produce unbiased estimates and are orders of magnitude faster than regression algorithms. At noise levels typical of many real applications, the neural networks are found to produce lower variance estimates than weighted nonlinear regression in the estimation of parameters from mono- and biexponential models. These results are primarily due to the inability of weighted nonlinear regression to converge. These results establish that artificial neural networks are powerful tools for estimating parameters for simple compartmental models.     

A pharmacodynamic approach to the estimate of carbamazepine autoinduction

Population-based pharmacokinetic prediction algorithms have been developed for several medications. A fundamental assumption has been that the kinetics remain constant over time. Carbamazepine (CBZ), however, induces its own metabolism in a concentration- and time-dependent manner. A Bayesian estimation program is presented that models the changing catabolic enzyme activity, linearly related to hepatic microsomal enzyme concentration, along with the serum drug concentration. An Emax model is used for enzyme formation with respect to drug concentration: elimination of enzyme activity is modeled as a first-order process. This program was tested in 22 drug-naive outpatients begun on CBZ monotherapy. The 1 week concentrations were used to prospectively predict concentrations at 1 month of therapy and were very close to actual measurements: prediction bias (mean error of prediction) = -0.1 micrograms/mL and precision (median absolute error of prediction) = 1.2 micrograms/mL. Comparison estimates, made by assuming a constant concentration/dose ratio, had bias = 2.6 micrograms/mL (p < 0.001) and precision = 2.2 micrograms/mL (p = 0.01). We conclude that (1) CBZ autoinduction is not complete after 1 week of therapy and (2) the methodology permits accurate estimation of CBZ pharmacokinetics.     

A graphical analysis method to estimate blood-to-tissue transfer constants for tracers with labeled metabolites

The Patlak graphical analysis technique is a popular tool for estimating blood-to-tissue transfer constants from multiple-time uptake data. Our objective was to extend this technique to tracers with labeled metabolites, the presence of which can cause errors in the standard Patlak analysis. METHODS: Based on previously described formulations, we generalized the graphical technique for use under specific conditions. To test the extended graphical approach, we applied the method to both simulated and patient data using a preliminary compartmental model for the PET tumor proliferation marker, 2-[11C]-thymidine. RESULTS: When given conditions are met, a linear relationship exists between the normalized tissue activity (tissue activity/blood activity) and a new set of graphical analysis basis functions, including a new definition of normalized time, which takes the presence of labeled metabolites into account. Graphical estimations of the tumor thymidine incorporation rate for simulated data were accurate and showed close agreement to the results of detailed compartmental analysis. In patient studies, the graphical and compartmental estimates showed good agreement but a somewhat poorer correlation than in the simulations. CONCLUSION: The extended graphical analysis approach provides an efficient method for estimating blood-tissue transfer constants for tracers with labeled metabolites.     

Fixation of canine tendons to metal

For the purpose of developing a method to attach tendons directly to the prosthesis, canine supraspinatus tendons were attached in vitro to a metallic surface, using 3 different fixation devices: a spiked polyacetal washer (Synthes), a spiked soft tissue fixation plate (Synthes), and a newly designed Enhanced Tendon Anchor (ETA), which straddled the tendon with interlocking spikes oriented at a 20-degree angle. 2 methods were used: 1) the tendon was fixed directly to the metallic surface, or 2) a bone block containing the tendon insertion was fixed to the metallic surface. The specimens were tested for initial fixation strength in tension to failure; intact bone-muscle-tendon-bone units were used as controls. Bone block fixations were stronger than direct tendon fixations when the spiked washer or the ETA was used; this was not true of the fixation plate. The ETA was stronger than the other techniques in ultimate strength in both direct tendon fixation and bone block fixation. The soft tissue fixation plate was found to be weaker than the other techniques in bone block fixation.     

Simple method to estimate cardiac output using first-pass data on RI angiography

In order to estimate cardiac output (CO) without using data equilibrium state, a simple index (cardiac output index, COI) was developed from the first-pass data as a ratio of the integrated radioactivity on the right ventricle to the total injected radioactivity. COI was well correlated with CO calculated by the conventional Stewart-Hamilton method (r = 0.894, p < 0.01), and thus, CO could be readily estimated from COI. This index might be useful to estimate CO since it can be obtained even with the agents which distribute to organs.     

Use of a correlational method to estimate a listener's weighting function for speech

The purpose of this study was to determine if it is feasible to use the correlational method (Lutfi, 1995; Richards and Zhu, 1994) to estimate how listeners use or weight the information contained within various frequency bands of speech. Three naturally spoken vowel-consonant-vowel (VCV) syllables (/aba/, /aga/, and /ada/) were presented monaurally to listeners. Each of the VCV waveforms were filtered into three separate frequency bands (i.e., low, mid, and high). Each band was then independently and randomly degraded at various signal-to-noise (S/N) levels (-7, -5, -3, -1, or +1). On each trial, listeners were asked to identify the VCV that was presented to them. For each trial, the S/N level of each frequency band, the stimulus that was presented, and the listener's responses were all recorded and stored in a file. From this trial-by-trial data, a point biserial correlation was computed between the listener's response (correct or incorrect identification) and the degradation within each frequency band. The stronger the correlation, the greater influence that given frequency band had on the listener's performance on the task. From these relations it was shown that it is possible to obtain a listener's weighting function for speech. Results showed that although most listeners weighted the mid-frequency band the greatest, several of the listeners used different weighting strategies to perform the task. Several methodological issues are discussed in regard to improving the future application of the correlational method to speech.     

A pessimistic estimate of the time required for an eye to evolve

Theoretical considerations of eye design allow us to find routes along which the optical structures of eyes may have evolved. If selection constantly favours an increase in the amount of detectable spatial information, a light-sensitive patch will gradually turn into a focused lens eye through continuous small improvements of design. An upper limit for the number of generations required for the complete transformation can be calculated with a minimum of assumptions. Even with a consistently pessimistic approach the time required becomes amazingly short: only a few hundred thousand years.     

Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial length

For single pliometric (lengthening) contractions initiated from optimal fiber length (Lf), the most important factor determining the subsequent force deficit is the work input during the stretch. We tested the hypothesis that regardless of the initial length, the force deficit is primarily a function of the work input. Extensor digitorum longus muscles of mice were maximally activated in situ and lengthened at 2 Lf/s from one of three initial fiber lengths (90, 100, or 120% of Lf) to one of three final fiber lengths (150, 160, or 170% of Lf). Maximal isometric force production was assessed before and after the pliometric contraction. No single mechanical factor, including the work input (r2 = 0.34), was sufficient to explain the differences in force deficits observed among groups. Therefore, the force deficit appears to arise from a complex interaction of mechanical events. With the data grouped by initial fiber length, the correlation between the average work and the average force deficit was high (r2 = 0.97-0.99). Consequently, differences in force deficits among groups were best explained on the basis of the initial fiber length and the work input during the stretch.     

原始疲劳质量模型描述方法改进

提出了用神经网络插值代替拉氏插值计算裂纹形成时间(TTCI)值,用极大似然估计代替均秩估计法估计分布参数的方法.考虑到仅对一组TTCI值进行参数估计具有较大的随机性,文中对每种参考裂纹尺寸对应的TTCI值均进行极大似然估计,得出多组TTCI分布参数;然后利用不同参考裂纹尺寸对应的TTCI分布参数之间的关系确定结构细节的当量初始缺陷尺寸分布参数.对某零件的疲劳实验及其原始疲劳质量分析证明了该方法的可行性和合理性.     

A population approach to initial dose selection

Before a drug can be marketed, an initial dose must be established. Sheiner et al. argue that a population approach leads to the most informed and rational decision making. We discuss the choice of an initial dose from both a predictive and estimative viewpoint. Our criteria are based upon evaluating the probabilities that a patient from the specified population obtains a response that is at least of a specified size. We demonstrate the approach using a simulation study and compare estimation of population parameters and initial dose using Bayesian and likelihood-based methods.     

A simple method of intraoperative limb length measurement in total hip arthroplasty

Avascular necrosis affects 3% of transplant recipients. In the lower limb, the femoral heads or condyles may be involved. We report the hitherto unrecorded complication of avascular necrosis of the calcaneum. Conservative management resulted in resolution without long-term complications.     

A model to estimate the potential economic benefits of measles eradication for the United States

Measles incidence is at a nadir in many parts of the world due to vaccination efforts. Although the technical feasibility of eradication has been acknowledged, financial and political commitment need to be concomitantly identified on the national and global level. We demonstrate the potential value of measles eradication by identifying the potential cost-savings to one country resulting from measles eradication. For the US, measles eradication would save $45 million annually. If achieved by the year 2010, the US would save $500 million to $4.1 billion depending on the year of elimination, post-eradication schedule and discount rate. Intensification of measles control efforts in the US beyond current levels would have minimal marginal benefits on disease burden reduction. Allocation of resources to achieve global measles eradication is the next level of efficiency which would provide substantial savings. Countries may adapt this model to estimate their savings for consideration of the required political and financial contribution towards a global measles eradication program.