David P. White, MD
- Harvard Medical School and Brigham and Women?
- Hospital, Boston, MA, USA
For example erectile dysfunction yohimbe purchase levitra 10mg without a prescription, Simon [23] abraded articular cartilage from human patellae and canine femoral heads with a stainless steel rotary file fast facts erectile dysfunction order levitra 10mg otc, measuring the depth of penetration with time and the amount of wear debris generated erectile dysfunction doctors in pa discount 10 mg levitra fast delivery. The latter researchers carried out several in vitro studies of wear of articular cartilage using bovine cartilage plugs or specimens in sliding contact against stainless steel plates impotence bicycle seat generic levitra 10mg without prescription. They developed a means of measuring cartilage wear by determining the hydroxyproline content of both the lubricant and solid wear debris. Using this system and technique, effects of variables such as time, applied load, and chemical modification of articular cartilage on wear and profile changes were determined. This work is of particular importance in that they addressed the question of cartilage wear and damage rather than friction, recognizing that wear and friction are different phenomena. Special note is also made of two researchers, Swann and Sokoloff, who considered biochemistry as an important factor in synovial joint lubrication. This was based on friction measurements using cartilage in sliding contact against a glass disc. An excellent summary of this work with additional references is presented in a chapter by Swann in the Joints and Synovial Fluid: I [6]. The research was extended to other in vitro friction tests using cartilage obtained from the nasal septum of cows and widely differing artificial surfaces [30]. As a result of this work, a new model of boundary lubrication by synovial fluid was proposed - the structuring of boundary water. The postulate involves adsorption of one part of a glycoprotein on a surface followed by the formation of hydration shells around the polar portions of the adsorbed glycoprotein; the net result is a thin layer of viscous "structured" water at the surface. This work is of particular interest in that it involves not only a specific and more detailed mechanism of boundary lubrication in synovial joints but also takes into account the possible importance of water in this system. The definition of "lubricating ability" was based on friction measurements made with a latex-covered stainless steel stud in oscillating contact against polished glass. The above summary of major synovial joint lubrication theories is taken from References 10 and 31 as well as the thesis by Burkhardt [33]. Two more recent studies are of interest since cartilage wear was considered although not as a part of a theory of joint lubrication. One finding was evidence of a load limit to lubrication of cartilage, beyond which high friction and damage occurred. A special note should be made concerning the doctoral thesis by Lawrence Malcom in 1976 [36]. This is an excellent study of cartilage friction and deformation, in which a device resembling a rotary plate rheometer was used to investigate the effects of static and dynamic loading on the frictional behavior of bovine cartilage. The contact geometry consisted of a circular cylindrical annulus in contact with a concave hemispherical section. It was found that dynamically loaded specimens in bovine synovial fluid yielded the Joint Lubrication 50-11 more efficient lubrication based on friction measurements. It does not, however, consider cartilage wear and damage except in a very preliminary way. And it does not consider the influence of fluid biochemistry on cartilage friction, wear, and damage. In short, the Malcom work represents a superb piece of systematic research along the lines of mechanical, dynamic, rheological, and viscoelastic behavior - one important dimension of synovial joint lubrication. The basic approach used involved in vitro tribological experiments using bovine articular cartilage, with an emphasis on the effects of fluid composition and biochemistry on cartilage wear and damage. In that study, bovine cartilage test specimens were loaded against a polished steel plate and subjected to reciprocating sliding for several hours in the presence of a fluid. Cartilage wear was determined by sampling the test fluid and determining the concentration of 4-hydroxyproline - a constituent of collagen. However, since the total quantities of collected fluids varied somewhat, the values shown in the bar graph should not be taken as exact or precise measures of fluid effects on cartilage wear.
Studies in animals and humans have shown that removal of the meniscus is a prelude to degenerative knees manifested by the development of osteoarthritis [Hede and Sarberg erectile dysfunction vacuum pumps reviews 10mg levitra otc, 1992; Shapiro and Glimcher erectile dysfunction treatment patanjali order 10 mg levitra, 1980] erectile dysfunction treatment abu dhabi quality levitra 10mg. Purified collagen materials have been used either as implants or have been extensively tested in clinical studies as implants without adverse effects zyrtec causes erectile dysfunction generic levitra 10 mg overnight delivery. The meniscus template can be fabricated from purified type I collagen fibers that are further crosslinked chemically to increase the stability and reduce the immunogenicity in vivo. In addition, small amounts of noncollagenous materials such as glycosaminoglycans and growth factors can be incorporated into the collagen matrix to improve the osmotic properties as well as the rate of tissue ingrowth. Since the primary structure of a collagen molecule from bovine is homologous to human collagen [Miller, 1984], the in vivo degradation of bovine collagen implant should be similar to the normal host tissue remodeling process during wound healing. For a resorbable collagen template, the matrix is slowly degraded by the host over time. It is known that a number of cell types such as polymorphonuclear leukocytes, fibroblasts, and macrophages, during the wound healing period, are capable of secreting enzyme collagenases which cleave a collagen molecule at 1/4 position from the C-terminal end of the molecule [Woolley, 1984]. The enzyme first reduces a collagen molecule to two smaller triple helices which are not stable at body temperature and are subsequently denatured to random coiled polypeptides. These polypeptides are further degraded by proteases into amino acids and short peptides that are metabolized through normal metabolic pathways [Nimni and Harkness, 1988]. Despite the safety record of collagen materials for implantation, during the process of preparing the collagen template, small amounts of unwanted noncollagenous materials could be incorporated into the device such as salts and crosslinking agents. Therefore, a series of biocompatibility testing must be conducted to ensure the residuals of these materials do not cause any safety issues. Thus, the size of the collagen template should match the tissue defect to be repaired. A properly sized meniscal substitute has been found to function better than a substitute which mismatches the physical dimension of the host meniscus [Rodkey et al. For a porous, elastic matrix such as the one designed from collagen for meniscal tissue repair, the shape of the meniscus is further defined in vivo by the space available between the femoral condyles and tibial plateau within the synovial joint. Thus, the apparent density is a direct measure of the empty space which is not occupied by the matrix material Biologic Biomaterials: Tissue-Derived Biomaterials (Collagen) 43-15 per se in the dry state. The apparent density is also directly related to the mechanical strength of a matrix. In weight-bearing applications, the apparent density has to be optimized such that the mechanical properties are not compromised for the intended function of the resorbable implant as described in the mechanical properties section. In order for cells to infiltrate into the interstitial space of a matrix, the majority of the pores must be significantly larger than the dimension of a cell such that both the cell and its cellular processes can easily enter the interstitial space. In a number of studies using collagen-based matrices for tissue regeneration, it has been found that pore size plays an important role in the effectiveness of the collagen matrix to induce host tissue regeneration [Chvapil, 1982; Dagalailis et al. Similar observations were also found to be true for porous metal implants in total hip replacement [Cook et al. The question of interconnecting pores may not be a critical issue in a collagen template as collagenases are synthesized by most inflammatory cells during wound healing and remodeling processes. The interporous membranes which exist in the noninterconnecting pores should be digested as part of resorption and wound healing processes. In order to accomplish this goal, one must first be certain that the initial mechanical properties are adequate for supporting the weight-bearing application. For example, compressing the implant with multiple body weights should not cause fraying of the collagen matrix material. It is also of particular importance to design an implant having an adequate and consistent suture pullout strength in order to reduce the incidence of detachment of the implant from the host tissue. The suture pullout strength is also important during surgical procedures as the lack of suture pull strength may result in retrieval and reimplantation of the template. In meniscal tissue repair the suture pullout strength of 1 kg has been found to be adequate for arthroscopically assisted surgery in simulated placement procedures in human cadaver knees, and this suture pullout strength should be maintained as the minimal strength required for this particular application.
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A more accurate representation of the control signal is Pmus (t) which drives the respiratory pump erectile dysfunction and diabetes leaflet buy levitra 20 mg with amex. The model of Poon and coworkers [1992] assumes a compound optimization criterion impotence treatment devices purchase 20mg levitra otc, Equation 11 erectile dysfunction with condom 10 mg levitra overnight delivery. The optimal Pmus (t) output is found by minimization of J subjects to the constraints set by the chemical and mechanical plants erectile dysfunction due to diabetes levitra 10mg mastercard, Equation 11. Because Pmus (t) is generally a continuous time function with sharp phase transitions, this amounts to solving a difficult dynamic nonlinear optimal control problem with piecewise smooth trajectories. Poon and colleagues [1992] have shown that the dynamic optimization model predicts closely the Pmus (t) trajectories under various conditions of ventilatory loading as well as respiratory muscle fatigue and weakness (Figure 11. In addition, the model also accurately predicts the ventilatory and breathing pattern responses to combinations of chemical and exercise stimulation and ventilatory loading [Poon et al. There is increasing evidence that the respiratory system is an adaptive control system [Poon, 1992a]. The first is that in order to adapt to changes, the system signals must be constantly fluctuating or persistently exciting. This should be readily satisfied by the respiratory system which is inherently oscillatory [Yamamoto, 1962] and chaotic [Donaldson, 1992; Sammon and Bruce, 1992]. Another requirement is that the system must be able to learn and then memorize the changes in the environment. Similar short and long-term memories have been identified recently in brain stem cardiorespiratory-related region in vitro [Zhou et al. It has been shown that learning and memory in the brain are sufficient to achieve an optimal behavior characterized by the chemoreflex response and isocapnic exercise response [Poon, 1991]. In other words, the controller gain may be adaptively increased or decreased depending on the coupling between the cause and effect of respiration. During exercise, ventilatory neural output and chemical feedback are strongly negatively correlated (since Spco2 has a large negative value) so that the controller learns to increase its gain, G0, in proportion to metabolic load. Respiratory short- and long-term potentiation have been variously reported as indicated above. The possibility of synaptic depression was recently demonstrated in the nucleus tractus solitarius of the medulla [Zhou et al. However, experimental and simulation data are presently lacking for verification of this conjecture. The classical chemostat model is useful in describing chemoreflex responses but may be too simplistic to explain the variety of system responses to exercise input and mechanical disturbances. This remarkable ability of the respiratory neural network is interesting from both biologic and engineering standpoints. Understanding how it works may shed light on not only the wisdom of the body [Cannon, 1932] but also on the design of novel intelligent control systems with improved speed, accuracy and economy. Simulations of a ventrolateral medullary neural network for respiratory rhythmogenesis inferred from spike train cross-correlation. The minimization of muscular energy expenditure during inspiration in linear models of the respiratory system. Central and peripheral chemoreflex loop gain in normal and carotid body-resected subjects. Neural network implementation of the three-phase model of respiratory rhythm generation. On a pseudo-rebreathing technique to assess the ventilatory sensitivity to carbon dioxide in man. Principles of feedback control and their application to the respiratory control system. Effects of various respiratory stimuli on the depth and frequency of breathing in man.
Different species have sensory systems that respond to stimuli that are important to them for survival erectile dysfunction drugs at walgreens buy levitra 20 mg with amex. Often one nervous system responds to conditions that are not sensed by another nervous system [4 erectile dysfunction grand rapids mi best 10 mg levitra,5] erectile dysfunction treatment garlic order levitra 10 mg otc. The transduction causes of erectile dysfunction in 50s effective levitra 10 mg, processing, and transmission of signals in any nervous system, produces a survival mechanism for an organism but only after these signals have been further modified by effector organs. Although the nerve impulses that drive a muscle as explained earlier are discrete events, a muscle twitch takes much longer to happen, a fact that allows for responses to overlap and produce a much smoother output. Neural control of motor activity of skeletal muscle is accomplished entirely by the modification of the muscle excitation, which involves changes in velocity, length, stiffness, and heat production. The importance of accurate timing of inputs, and the maintenance of this timing across several synapses, is obvious in sensory pathways of the nervous system. Cells are located next to other cells that have overlapping or adjacent receptive or motor fields. The dendrites provide important and complicated sites of interactions as well as channels of variable effectiveness for excitatory inputs, depending on their position relative to the cell body. Among the best examples are the cells of the medial superior olive in the auditory pathway. These cells have two major dendritic trees extending from opposite poles of the cell body. One receives synaptic inhibitory input from the ipsilaterial cochlear nucleus and the other from the contralateral, which normally is an excitatory input. When a sound is present at the contralateral side, most cells are excited while ipsilateral sounds cause inhibition. It has been shown that the cells can go from complete excitation to full inhibition with a difference of only a few hundred milliseconds in arrival time of the two inputs. The question then arises: how does the nervous system put together the signals available to it so that a determination of our output takes place To arrive at an understanding of how the nervous system intergrates incoming information at a given moment of time, we must understand that the processes that take place depend both on cellular forms and a topological architecture as well as on the physiological properties that relate input to output. One of the important factors determining weighting is the area of synaptic contact. Electronic spread is the means of mixing, smoothing, attenuating, delaying, and summing postsynaptic potentials. The spatial distribution of input is often not random but systematically restricted. Also, the wide variety of characteristic geometries of synapses is, no doubt, important not just for the weighting of different combinations of inputs. When repeated stimuli are presented at various intervals at different junctions, higher amplitude synaptic potentials are generated, if the intervals between them are not too short or too long. If the response lasts longer than the interval between impulses, so that the second response rises from the residue of the first, then it is called temporal summation. If in addition, the response increment due to the second stimulus is larger than the previous one, then it is facilitation. Facilitation is an important function of the nervous system and is found in quite different forms and durations ranging from a few milliseconds to tenths of seconds. Facilitation may grade from forms of sensitization to learning, especially at long intervals. A special case is the so-called posttetanic potentiation which is the result of high frequency stimulation for long periods of time (about 10 sec). The latter is an interesting case since, no effects can be seen during stimulation but Nervous System 3-5 afterward any test stimulus at various intervals creates a marked increase in response up to many times more than the "tetanic" stimulus. Antifacilitation, is the phenomenon where a decrease of response from the neuron is observed at certain junctions, due to successive impulses. Both facilitation and antifacilitation may be observed on the same neuron but when different functions are performed. Since what is communicated is nothing more than impulses - spike trains - the only basic variables in a train of events are the number of and the interval between spikes. With respect to that, the nervous system acts like a pulse coded analog device since the intervals are continuously graded. There exists a distribution of interval lengths between individual spikes, which in any sample can be expressed by the shape of the interval histogram.
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