The importance of the elastic and plastic components of strain in tensile and compressive fatigue of human cortical bone in relation to orthopaedic biomechanics.

The longevity, success, or failure of an orthopaedic implant is dependent on its osseointegration especially within the initial six months of the initial surgery. The development of strains plays a crucial role in both bone modelling and remodelling. For remodelling, in particular, strains of substantial values are required to activate the osteoblastic and osteoclastic activity for the osseointegration of the implant. Bone, however, is subject to "damage" when strain levels exceed a certain threshold level. Damage is manifested in the form of microcracks; it is linked to increased elastic strain amplitudes and is accompanied by the development of "plastic" (irrecoverable, residual) strains. Such strains increase the likelihood for the implant to subside or loosen. The present study examines the rates (per cycle) by which these two components of strain (elastic and "plastic") develop during fatigue cycling in two loading modes, tension and compression. The results of this study show that these strain rates depend on the applied stress in both loading modes. It also shows that elastic and plastic strain rates can be linked to each other through simple power law relationships so that one can calculate or predict the latter from the former and vice versa. We anticipate that such basic bone biomechanics data would be of great benefit to both clinicians and bioengineers working in the field of FEA modelling applications and orthopaedic implant surgery.

Strain patterns during tensile, compressive, and shear fatigue of human cortical bone and implications for bone biomechanics.

It is a common theme in basic bone biomechanics and in biomechanical applications that much of the behavior can be determined and is dictated by the level of strain, whether this pertains to bone physiology, bone remodeling, osseoinduction, osseointegration, or the development of damage. The development of damage, demonstrated by stiffness loss measurements, has already been reported in detail in the literature. However, the systematic study of the development of "plastic" (residual) strains, which are associated with the inelastic mechanical behavior of bone tissue, has generally been overlooked. The present study compares the rates at which the elastic (e(a)) and plastic components (e(p)) of strain developed during tensile, compressive, and shear fatigue in human cortical bone of six individuals aged between 53 and 79 years. The overall hypothesis of this investigation is that there is a common underlying factor in the damage-related behavior of bone, which may allow us to link together the various aspects of the damage related behavior of bone. The rate of development of plastic strain (Deltae(p)/DeltaN) and the rate of growth in elastic strain amplitude (Deltae(a)/DeltaN) are described as a function of the stress (sigma), and/or stress normalized by the modulus of elasticity (sigma/E). The implications of our findings are discussed with respect to simple models/mechanisms, which may underlie the observed behavior.

Effect of fluid forcing on vestibular hair bundles.

A dynamic 3-D hair bundle model including inertia and viscous fluid drag effects based on the finite element method is presented. Six structural components are used to construct the hair bundle--kinocilium, stereocilia, upper lateral links, shaft links, tip links, and kinocilial links. Fluid drag is distributed on the surface of cilia columns. Bundle mechanics are analyzed under two distinct loading conditions: (1) drag caused by the shear flow of the surrounding endolymph fluid (fluid-forced), (2) a single force applied to the tip of the kinocilium (point-forced). A striolar and a medial extrastriolar vestibular hair cell from the utricle of a turtle are simulated. The striolar cell bundle shows a clear difference in tip link tension profile between fluid-forced and point-forced cases. When the striolar cell is fluid forced, it shows more evenly distributed tip link tensions and is far more sensitive, responding like an on/off switch. The extrastriolar cell does not show noticeable differences between the forcing types. For both forcing conditions, the extrastriolar cell responds serially--the nearest tip links to the kinocilium get tensed first, then the tension propagates to the farther tip links.

Mood and cognitive performance effects of "energy" drink constituents: caffeine, glucose and carbonation.

Three studies using healthy volunteers (n = 271) investigated the effects of caffeine, carbohydrates and carbonation in functional "energy" drinks (EDs) with the aim of determining their benefit in every-day life. The results showed caffeine to be the main ED constituent responsible for the effects found, with possible minor, relatively weak effects of carbohydrates. EDs were found to improve and/or maintain mood and performance during fatiguing and cognitively demanding tasks relative to placebo. In terms of absolute values, EDs maintained levels of arousal compared to a deterioration in arousal where placebo was consumed. These effects were found in caffeine-deprived participants, and so may be largely due to "withdrawal reversal". There were only minor differences in the effects of water vs. "sensory-matched" placebo, supporting previous findings indicating that the type of placebo does not alter the conclusions drawn about the effects of the full ED. Finally, carbonation had various effects on mood, some of which were present immediately following consumption, others were consistent with slower absorption of caffeine (and possibly carbohydrates) from carbonated drinks.

A finite element method for mechanical response of hair cell ciliary bundles.

This paper describes the development of a methodology for performing a mechanical analysis of hair cell ciliary bundles. The cilia were modeled as shear deformable beams, and interconnections were modeled as two-force members. These models were incorporated into software, which performs a finite element analysis of a user-defined bundle. The algorithm incorporates aspects of the bundle such as geometric realignment and buckling of compressed side links. A sample bundle is introduced and results of modeling it are presented.

Replacement of dietary fat with sucrose polyester: effects on energy intake and appetite control in nonobese males.

In previous experiments using the fat substitute sucrose polyester (SPE, or olestra), no compensatory response was observed on day 2 after experimental manipulations, which reduced the percentage of energy from fat to approximately equal to 30% from 40% on day 1. In the present study a more severe manipulation was made; the amount of energy from fat was reduced from 32% to 20% to determine whether such a reduction would provoke any physiologic or behavioral response. Subjects came to the unit for two, 2-d test sessions. Intake on day 1 was fixed: subjects were given meals containing either control fat (11319 kJ, 32% of energy as fat) or SPE (9561 kJ, 20% of energy as fat). On day 2, intake was ad libitum. On day 1 subjects rated themselves as more hungry while consuming the fat-substituted meals than when consuming the control meals and they disclosed greater hunger in the end-of-day questionnaires. The effect of the manipulation was carried over into day 2. By the end of day 2, subjects had compensated for 74% of the energy (fat) deficit caused by the previous day's manipulation. These results differ from those obtained when fat was reduced from 40% to 30% of energy; this more severe reduction reveals that a reduction in fat of this size can lead to a biobehavioral response. Together, these data suggest that people could change their diet to meet dietary guidelines; however, if a more severe reduction is attempted, adherence may be made more difficult by the strength of the compensatory response.

Fat substitution and food intake: effect of replacing fat with sucrose polyester at lunch or evening meals.

The objective of the present study was to determine the effect of replacement of fat by sucrose polyester (SPE) within a lunch or evening meal on subsequent energy intake and appetite control. The 2 x 2 design was intended to examine the effect on appetite of reducing the total energy and fat content of a meal (lunch or dinner) by replacement of natural fat with 55 g SPE. The effects were monitored by measuring motivation to eat or actual food consumption during the remainder of the test day (day 1) and throughout the following day (day 2). The 2 x 2 design yielded four conditions which were a control meal (5192 kJ, 73.2 g fat) and a fat-replaced meal (3305 kJ, 54.6 g SPE, 24 g fat) at midday (lunch) or in the early evening (dinner). No significant differences were seen in ad lib. energy intake after the test meals on day 1 or day 2. Certain differences were detected in fat intake on day 2 but these did not suggest nutrient compensation in response to the fat replacement. Subjective assessment of motivation to eat did not indicate that the fat-reduced meal had a weaker satiating efficiency than the control meal. A reduction in fat content, using fat replacement, did not reduce the satiating efficiency of a test meal given at lunch or dinner. No energy or macronutrient compensation occurred following the reduction in energy or fat intake during the rest of the test day or during the whole of the next day.

Control of human appetite: implications for the intake of dietary fat.

The human appetite system contains central and peripheral mechanisms that interact with environmental features, especially with the physical and nutrient composition of the food supply. Foods varying in nutrient composition exert different physiologic effects, some of which function as satiety signals. High-fat diets (low food quotient) lead to high levels of energy intake. This effect is termed passive overconsumption and overcomes fat-induced physiological satiety signals. High-fat foods exert a weak effect on satiation (intra-meal satiety), and fat has a weaker effect, joule for joule, on postingestive satiety than do other macronutrients. The frequency of obesity is greater among high-fat than low-fat consumers. However, the development of obesity on a high-fat diet is not a biological inevitability. The investigation of people who resist the weight-inducing properties of high-fat diets is a key research strategy. Understanding the appetite control system suggests behavioral, nutritional, and pharmacologic strategies for modifying dietary fat intake.

Theoretical mechanical frequency response of the otolithic organs.

A distributed parameter model, which consisted of three coupled partial differential equations, describing the mechanical response of the otolithic organs, was used to develop a system mechanical transfer function. The equations were Laplace transformed and combined to yield a transfer function for otoconial layer displacement relative to an acceleration stimulus. Acceleration is either skull acceleration or gravity. In addition, transfer functions for the gel layer and endolymph fluid layer were also developed which included a spatial coordinate as a transfer function variable. Frequency response diagrams were constructed from the transfer functions, using numerical values of nondimensional parameters developed in an earlier study. The otoconial layer transfer function was compared to physiologic data on utricular primary afferent neurons and there was good agreement except at low frequencies. The discrepancy between the theoretical transfer function and the primary afferent response can be attributed to contributions of the spike encoder, which has been measured experimentally, additional non-mechanical components in the transduction process, and even non-linear elements in the mechanical system.

Dietary fat and the control of energy intake: evaluating the effects of fat on meal size and postmeal satiety.

Three separate experiments in lean subjects confirmed that a 1.52-MJ (362-kcal) carbohydrate supplement at breakfast suppressed appetite 90 min later but had no effect on a test meal given after 270 min. A 1.52-MJ (362-kcal) fat supplement produced no detectable action on measures of appetite at any time point. Therefore, fat and carbohydrate do not have identical effects on the appetite profile. In a further study in obese subjects, a novel experimental design was used to assess the satiating efficiency and compensatory response of fat. Eating from a range of either high-fat or high-carbohydrate foods, obese subjects voluntarily consumed twice as much energy from the fat items, thereby indicating a weak action of fat on satiation. In turn, this large intake of fat exerted a disproportionately weak effect on satiety. These studies suggest that the appetite-control system may have only weak inhibitory mechanisms to prevent the passive overconsumption of dietary fat. The results indicate how this action could induce a positive energy balance and lead to a gradual upward drift in body mass index.

A model for otolith dynamic response with a viscoelastic gel layer.

The otolith organs were modeled mathematically as a 3-element system consisting of a viscous endolymph fluid in contact with a rigid otoconial layer that is attached to the skull by a gel layer. The gel layer was considered to be viscoelastic solid, and was modeled as a simple Kelvin material. The governing differential equations of motion were derived and nondimensionalized, yielding 3 nondimensional parameters: nondimensional density, nondimensional viscosity, and nondimensional elasticity. The equations were solved using finite difference techniques on a digital computer. By comparing the model's response with previous experimental research, values for the nondimensional parameters were found. The results indicate that the inclusion of viscous and elastic effects in the gel layer are necessary for the model to produce otoconial layer deflections that are consistent with physiologic displacements. Future experimental data analysis and mathematical modeling effects should include viscoelastic gel layer effects, as this is a major contributor to system damping and response.

Correction of uremic cellular injury with a protein-restricted amino acid-supplemented diet.

Untreated patients with uremia show an abnormally low resting transmembrane potential (Em) of skeletal muscle cells. This finding corresponds to impaired sodium transport. Adequate hemodialysis corrects this abnormality. Toxins derived from protein precursors have been implicated as the hypothetical cause of impaired transport and membrane depolarization in untreated uremia. To inferentially examine this hypothesis in further detail, we deliberately reduced dialysis time until Em fell in six uremic patients in whom it had been previously corrected. When Em fell, we examined the effect of reducing crude protein in their diet in conjunction with adding an essential amino acid supplement. Five of six patients who complied with the diet showed correction of their abnormally low Em despite continued reduction of dialysis time. These findings support the notion that in patients with uremia, a product of crude dietary protein may be responsible for membrane depolarization and, in addition, direct measurement of resting muscle transmembrane potential may be a useful index to determine adequacy of dialysis therapy.

Thrombotic thrombocytopenic purpura after a dogbite.

A man bitten by a pet dog had fulminant thrombotic thrombocytopenic purpura within 72 hours. Rhabdomyolysis was severe and acute anuric renal failure was present. The suspected causative agent was Pastuerella multocida or clostridia with possible endotoxemia, though early treatment precluded a definitive diagnosis. The patient responded dramatically to a combined therapeutic approach of antibiotics, steroids, splenectomy, and supportive hemodialysis.

Resting skeletal muscle membrane potential as an index of uremic toxicity. A proposed new method to assess adequacy of hemodialysis.

Electrochemical disturbances of skeletal muscle cells in untreated uremia are characterized by an increase in the intracellular sodium and chloride content, a decrease in intracellular potassium, and a low resting membrane potential. In this study, we have reexamined the foregoing and, in addition, have examined the effects of hemodialysis. Three groups of patients were studied. In the first group of 22 uncomplicated uremic patients, whose creatinine clearance (Ccr) ranged from 2 to 12 cm(3)/min per 1.73 m(2), resting transmembrane potential difference (Em) of skeletal muscle cells was measured. In each of the nine patients whose Ccr ranged between 6.3 and 12 cm(3)/min, the Em was normal (i.e., -90.8+/-0.9 mV, mean+/-SEM). However, as Ccr dropped below 6.3 cm/min, the Em became progressively reduced and assumed a linear relationship with the Ccr. In the second study, nine individuals with end-stage renal disease, whose mean Ccr was 4.3 cm(3)/min, underwent measurement of Em and intracellular electrolyte concentration before and after 7 wk of hemodialysis. Before dialysis, the Em was -78.5+/-2.1 mV, intracellular sodium and chloride were elevated, and the intracellular potassium was reduced. After 7 wk of hemodialysis the Em rose to -87.8+/-1.3 mV, and the intracellular sodium, chloride, and potassium became normal. In the third study, seven patients who were stable on 6-h thrice-weekly dialysis were studied before and after reduction of dialysis to 6 h twice weekly. In those individuals whose Em remained normal after 6 wk, dialysis time was reduced further. On thrice-weekly dialysis the Em was -91.2+/-1.0 mV. With reduced dialysis, the Em fell to -80.1+/-0.8 mV (P < 0.001). In each case, the Em became abnormal before significant signs or symptoms of uremia were noted. These findings demonstrate that end-stage renal disease is associated with serious electrochemical changes in the muscle cell which are reversed by hemodialysis and recur when dialysis time is reduced. Thus, serial observations of muscle Em may be a potentially powerful tool to assess adequacy of dialysis therapy.

Hypophosphatemia and rhabdomyolysis.

Clinical observations suggest that overt rhabdomyolysis may occur if severe hypophosphatemia is superimposed upon a pre-existing subclinical myopathy. To examine this possibility, a subclinical muscle cell injury was induced in 23 dogs by feeding them a phosphorus- and calorie-deficient diet until they lost 30% of their original weight. To induce acute, severe hypophosphatemia in the animals after partial starvation, 17 of the dogs were given large quantities of the same phosphorus-deficient diet in conjunction with an oral carbohydrate supplement, which together provided 140 kcal/kg per day. After phosphorus and caloric deprivation, serum phosphorus and creatine phosphokinase (CPK) activity were normal. Total muscle phosphorus content fell from 28.0+/-1.3 to 26.1+/-2.5 mmol/dg fat-free dry solids. Sodium, chloride, and water contents rose. These changes resembled those observed in patients with subclinical alcoholic myopathy. When studied after 3 days of hyperalimentation, the animals not receiving phosphorus showed weakness, tremulousness, and in some cases, seizures. Serum phosphorus fell, the average lowest value was 0.8 mg/dl (P <0.001). CPK activity rose from 66+/-357 to 695+/-1,288 IU/liter (P <0.001). Muscle phosphorus content fell further to 21.1+/-7.7 mmol/dg fat-free dry solids (P <0.001). Muscle Na and Cl contents became higher (P <0.01). Sections of gracilis muscle showed frank rhabdomyolysis.6 of the 23 phosphorus- and calorie-deprived dogs were also given 140 kal/kg per day but in addition, each received 147 mmol of elemental phosphorus. These dogs consumed their diet avidly and displayed no symptoms. They did not become hypophosphatemic, their CPK remained normal, and derangements of cellular Na, Cl, and H(2)O were rapidly corrected. The gracilis muscle appeared normal histologically in these animals. These data suggest that a subclinical myopathy may set the stage for rhabdomyolysis if acute, severe hypophosphatemia is superimposed. Neither acute hypophosphatemia nor rhabdomyolysis occur if abundant phosphorus is provided during hyperalimentation.

Acute renal failure following halothane anesthesia.

Acute renal failure was observed postoperatively in a patient after halothane anesthesia. The clinical and pathologic findings in this case were remarkably similar to those found in patients with renal failure after methoxyflurane anesthesia.