Diaphragm performance during maximal voluntary ventilation in chronic obstructive pulmonary disease

In normal subjects 2 min of maximal voluntary hyperventilation results in failure of tension generation and low-frequency fatigue of the diaphragm. Patients with severe chronic obstructive pulmonary disease (COPD) do not develop diaphragm fatigue during exhaustive treadmill exercise despite excessive inspiratory muscle loading and we hypothesized that they might be relatively resistant to the development of diaphragm fatigue during maximal ventilation. In six patients with severe COPD (mean FEV1 0.671) we therefore loaded the diaphragm using 2 min of maximal isocapnic ventilation (MIV). Initial mean ventilation was 28.6 L/min and diaphragm pressure-time product (PTPdi) 602 cm H2O x s/min; these values were sustained throughout MIV without significant decline. Mean twitch transdiaphragmatic pressure (Tw Pdi) was 19.7 cm H2O 25 min after a control run and 20.5 cm H2O at the same time after MIV [corrected]. Compared with normal subjects previously studied in our laboratory (Hamnegard, C.-H., et al. Eur. Respir. J. 1996;9:241-247) the reduction in PTPdi was disproportionately greater than the reduction in Tw Pdi. We conclude that, unlike normal subjects, 2 min of MIV causes neither failure of diaphragm performance nor low-frequency diaphragm fatigue in patients with severe COPD. It is likely that the diaphragm makes a relatively limited contribution to the generation of maximal levels of ventilation in severe COPD.     

Smooth muscle cell to elastic lamina connections in developing mouse aorta. Role in aortic medial organization

BACKGROUND: The structural and functional intigration of smooth muscle cells and elastic laminae in the aortic media is not well established. Detailed information concerning normal ultrastructural features of the aortic media will provide a better understanding of the medial changes that occur in vascular diseases such as hypertension and aortic aneurysms. EXPERIMENTAL DESIGN: The ultrastructural development and organization of connections between smooth muscle cells and elastic laminae in the mouse aortic media were studied by light and electron microscopy. RESULTS: Early in development, the smooth muscle cells become linked to the elastic laminae by bundles of microfibrils. These microfibrils become progressively infiltrated with elastin so as to form extensions of elastin from the elastic laminae in the adult media. Each elastin extension spans obliquely from the elastic lamina to the surface of the smooth muscle cell where it attaches in a region of membrane occupied by an intracellular membrane-associated dense plaque. On the cytoplasmic face of the plaque, a contractile filament bundle penetrates and anchors in an orientation similar to that of the extracellular elastin extension. The contractile filament bundle traverses the cell obliquely and anchors in a dense plaque on the opposite side of the cell that is in turn linked to the next elastic lamina by another elastin extension. The extracellular elastin extensions and the intracellular contractile filament bundles thus form a "contractile-elastic unit," a continuous line of structures that links adjacent elastic laminae. The oblique orientation of the contractile-elastic units reverses direction in successive smooth muscle cell layers in a herringbone-like pattern. Thus, tension transmitted to one elastic lamina by the smooth muscle cells on either side results in a uniform force exerted on the elastic lamina in one circumferential direction, that on the adjacent elastic laminae being in the opposite direction. CONCLUSIONS: Results from this study demonstrate the presence of smooth muscle cell to elastic lamina connections that form early in development as contractile-elastic units; basic units of aortic medial ultrastructure. The overall organization of the contractile-elastic units within the aortic media is proposed to provide a means for coordinating contractile and elastic tensions in response to mechanical stresses imposed on the vessel wall.     

The diaphragm in emphysema

Because of hyperinflation, the diaphragm of emphysematous patients operates at a disadvantageous position which affects its mechanical arrangement, modifies the configuration of its zone of apposition, increases its radius of curvature, and decreases its muscle fiber length below optimal configuration. The diaphragm in emphysema therefore displays a suboptimal configuration limiting its ability to function properly but shows no inherent structural insufficiency, unless its contractility is impaired by significant arterial blood gas anomalies or severe malnutrition. The demand imposed on the diaphragm in emphysema is increased by both hyperinflation and air-flow obstruction. With altered performance of the diaphragm and increased demand, force reserve is diminished and diaphragmatic fatigue may occur; this imbalance is targeted in some treatment modalities of emphysema such as pulmonary rehabilitation programs and lung volume reduction surgery.     

Test of Stice''s dual pathway model: dietary restraint and negative affect as mediators of bulimic behavior

Many investigators have used animal models to clarify the role of the human anterior cruciate ligament (ACL). Because none of these models are anatomically and biomechanically identical to the human ACL, there exists a need for an objective comparison of these models. To do this, we used a universal force-moment sensor to measure and compare the in situ forces, including magnitude and direction, of the ACL and the anteromedial (AM) and posterolateral (PL) bundles of human, pig, goat, and sheep knees. An Instron was used to apply 50 and 100 N anterior tibial loads at 90 degrees of knee flexion, while a universal force-moment sensor was used to measure the forces applied by the ACL to the tibia, the in situ force of the ACL. We found significant differences between the magnitude of force experienced by the goat and sheep ACL and AM and PL bundles when compared with the human ACL and AM and PL bundles. Also, the direction of the in situ force in the ACL and AM bundles of the goat and sheep were different from the human. The pig knee differed from the human only in the magnitude and direction of the in situ force in the PL bundle in response under anterior tibial loading. A tally of the significant differences between the animal models and the human knees indicates that goat and sheep knees may have limitations in modeling the human ACL, while the pig knee may be the preferred model for experimental studies.     

N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.     

Role of caffeine in combined analgesic drugs from the point of view of experimental pharmacology

3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.     

Aberrations of spherocylindrical spectacle lenses

A procedure has been developed for tracing a bundle of rays through and ophthalmic lens and a schematic eye with its primary line of sight pointed through various parts of the lens. A bundle of eight rays can provide data for assessing the quality of the image formed by such a system. To test the procedure and to generate data which can help in selecting a method for evaluating image quality, we selected a single lens as an example. The lens selected has a spherical back surface (-5.00 diopters) and a toric front surface (+15.00 diopters in the vertical and /10.00 diopters in the horizontal). It has a center thickness of 5 mm and glass of index 1.523. Spot diagrams were generated with the eye pointed in various directions through the ophthalmic lens. The data generated showed that peripheral bundles which fall between the principal meridians emerge as astigmatic bundles. This leads to the proposal that blur circle theory can be used for evaluating the quality of the optical image and that it suffices in the case of a spherocylindrical ophthalmic lens to base the tolerances for refractive power on measurements made in the principal meridians.     

Control of human jaw elevator muscle activity during simulated chewing with varying bolus size

During chewing, a small part of the observed muscle activity is needed for the basic open-close movements of the mandible, and additional muscle activity (AMA) is needed to overcome the resistance of the food. The AMA consists of two contributions: a large peripherally induced contribution, starting after food contact and a small anticipating contribution, starting before food contact. We investigated whether the latencies of these contributions depend on the expected or actual bolus size. Subjects made rhythmic open-close movements near their natural chewing frequency controlled by a metronome. This frequency was determined while the subjects were chewing gum. Food resistance was simulated by an external force, acting on the jaw in a downward direction during part of the closing movement. Bolus size was simulated by the jaw gape at which the force started. Jaw movement and surface EMG of the masseter and anterior temporal muscles on both sides and the suprahyoid muscles were recorded during experiments in which the jaw gape at which the force started was varied. The peripherally induced contribution to the AMA started about 20 ms after the onset of the force, irrespective of the jaw gape at which the force started. It is concluded that the onset of this contribution depends solely on food contact in the actual cycle. The function of the observed mechanism for jaw elevator muscle control may be to enable a highly automatic control of the muscle activity required to overcome the resistance of food of different hardness and different size. The onset of the anticipating contribution to the AMA showed neither a relationship with the actual jaw gape at which force onset occurred nor with the expected jaw gape of force onset. It is suggested that the onset of the anticipating AMA is related to the jaw gape at the onset of closing. The function of this contribution may be the regulation of the mechanical response of the jaw after an expected disturbance of the closing movement by food contact, by tuning the muscle stiffness to the expected hardness of the food.     

EMG responses to maintain stance during multidirectional surface translations

To characterize muscle synergy organization underlying multidirectional control of stance posture, electromyographic activity was recorded from 11 lower limb and trunk muscles of 7 healthy subjects while they were subjected to horizontal surface translations in 12 different, randomly presented directions. The latency and amplitude of muscle responses were quantified for each perturbation direction. Tuning curves for each muscle were examined to relate the amplitude of the muscle response to the direction of surface translation. The latencies of responses for the shank and thigh muscles were constant, regardless of perturbation direction. In contrast, the latencies for another thigh [tensor fascia latae (TFL)] and two trunk muscles [rectus abdominis (RAB) and erector spinae (ESP)] were either early or late, depending on the perturbation direction. These three muscles with direction-specific latencies may play different roles in postural control as prime movers or as stabilizers for different translation directions, depending on the timing of recruitment. Most muscle tuning curves were within one quadrant, having one direction of maximal activity, generally in response to diagonal surface translations. Two trunk muscles (RAB and ESP) and two lower limb muscles (semimembranosus and peroneus longus) had bipolar tuning curves, with two different directions of maximal activity, suggesting that these muscle can play different roles as part of different synergies, depending on translation direction. Muscle tuning curves tended to group into one of three regions in response to 12 different directions of perturbations. Two muscles [rectus femoris (RFM) and TFL] were maximally active in response to lateral surface translations. The remaining muscles clustered into one of two diagonal regions. The diagonal regions corresponded to the two primary directions of active horizontal force vector responses. Two muscles (RFM and adductor longus) were maximally active orthogonal to their predicted direction of maximal activity based on anatomic orientation. Some of the muscles in each of the synergic regions were not anatomic synergists, suggesting a complex central organization for recruitment of muscles. The results suggest that neither a simple reflex mechanism nor a fixed muscle synergy organization is adequate to explain the muscle activation patterns observed in this postural control task. Our results are consistent with a centrally mediated pattern of muscle latencies combined with peripheral influence on muscle magnitude. We suggest that a flexible continuum of muscle synergies that are modifiable in a task-dependent manner be used for equilibrium control in stance.     

Influence of lung volume and electrode position on electromyography of the diaphragm

In cats anesthetized with Nembutal, electromyograms of the diaphragm (Edi) were recorded from an anchored esophageal electrode, a pair of silver hooks inserted in the paratendinous region, and a pair of silver hooks and a pair of clips of small surface inserted in the costal region of the diaphragm facing the rib cage at FRC but covered with lung tissue at FRC + 80 ml. When single supramaximal electrical stimuli were applied to an isolated phrenic nerve, changes in lung volume from RV to near TLC had a negligible effect on muscle potentials from esophageal or paratendinous hooks, but increased the amplitude of potentials recorded from peripheral hooks and clips. In addition, it was found that small displacements of the esophageal electrode caused substantial changes in the amplitude of the recorded muscle potentials. The integration of the Edi spontaneously generated during occluded inspirations, recorded from paratendinous hooks and the esophageal electrode was linearly related to transdiaphragmatic pressure up to 50 cmH2O at all lung volumes. Above that level, esophageal electrode recordings showed a curvilinear Edi/Pdi relationship, while hook recordings showed a rectilinear relationship.     

Tension and bending, but not compression alone determine the functional adaptation of subchondral bone in incongruous joints

In the present study, we tested the hypothesis that tension and bending, rather than compression alone, determine the functional adaptation of subchondral bone in incongruous joints. We investigated whether tensile stresses in the subchondral bone of the humero-ulnar articulation are affected by the direction of muscle and joint forces, and whether the tensile stresses are large enough to cause microstructural adaptation, specifically a preferential alignment of the trabeculae and the subchondral collagen fibres. Using a previously validated finite element model of the human humero-ulnar joint, we calculated the contact pressure, the principal compressive and tensile stresses, and the strain energy density in the subchondral bone for various flexion angles. A bicentric (ventro-dorsal) pressure distribution was found in the joint at 30 degrees to 120 degrees of flexion, with contact pressures of up to between 2.5 and 3 MPa in the ventral and dorsal aspects of the ulnar joint surface, but less than 0.5 MPa in the centre. The principal tensile stress in the subchondral bone of the trochlear notch quantitatively exceeded the principal compressive stress at low flexion angles (maximum 8.2 MPa), and the distribution of subchondral strain energy density differed substantially from that of the contact stress (r=-0.72 at 30 degrees and r=+0.58 at 90 degrees of flexion). No important tensile stress was computed in the trochlea humeri. On contact radiography, we found sagittally orientated subarticular trabeculae in the notch, running tangential to the surface. Furthermore, we observed sagittally orientated split lines in the subchondral bone of the notch of 20 cadaver joints, suggesting a ventro-dorsal orientation of the collagen fibres. The trochlea humeri, on the other hand, did not show a preferential direction of the subchondral split lines, these findings confirming the predictions of tensile stresses in the model. We conclude that, due to the important contribution of tension to subchondral bone stress, the distribution of subchondral density cannot be directly employed for assessing the long term distribution of joint pressure at the cartilage surface. The magnitude of the tensional stress varies considerably with the direction of the muscle and joint forces, and it appears large enough to cause functional adaptation of the subchondral bone on a microstructural level.     

Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.     

Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.     

Hypertrophic pyloric stenosis in infancy. An analysis of treatment outcome

The anatomy of the double or bifid zygomaticus major muscle is investigated in a series of 50 hemifacial cadaver dissections. The double zygomaticus major muscle represents an anatomical variation of this muscle of facial expression. This bifid muscle originates as a single structure from the zygomatic bone. As it travels anteriorly, it then divides at the sub-zygomatic hollow into superior and inferior muscle bundles. The superior bundle inserts at the usual position above the comer of the mouth. The inferior bundle inserts into the modiolus below the corner of the mouth. The incidence of the double zygomaticus major muscle was 34% in the present study, as it was found to be present in 17 of 50 cadaver dissections. This study shows that variation in the individual morphology of the mimetic muscles can be a common finding. Clinically, the double or bifid zygomaticus major muscle may explain the formation of cheek "dimples." The inferior bundle was observed in several specimens to have a dermal attachment along its mid-portion, which tethers the overlying skin. When an individual with this anatomy smiles, traction on the skin may create a dimple due to this dermal tethering effect.     

Adrenergic innervation of the urinary bladder body in the cat with special reference to structure of the detrusor muscle: an immunohistochemical study of noradrenaline and its synthesizing enzymes

The distribution of adrenergic nerves in the body detrusor muscle of the cat urinary bladder was studied by means of the immunohistochemical identification of noradrenaline (NA) and the NA synthesizing enzymes tyrosine hydroxylase, aromatic L-aminoacid decarboxylase and dopamine beta-hydroxylase. We identified the basic structural organization of the detrusor muscle, which had previously been described as lacking discernible layers. In the lateral wall, both outer longitudinal and inner circular muscle bundles were present, the latter extending in both anterior and posterior directions. The posteriorly running bundles came to lie on the outside of the posterior wall where they enabled recognition of inner longitudinal muscle bundles. Those running anteriorly were dispersed to enter the longitudinal bundles in the anterior wall. NA-immunoreactive nerve fibers in the detrusor muscle of the bladder were found to be similar to those immunoreactive for NA synthesizing enzymes in both distribution and density. In the upper and middle bladder body--including the dome (apex)--immunoreactive nerve fibers were always more abundant in the outer part of the detrusor muscle than in the inner part, regardless of the course of muscle bundles. Even in individual muscle bundles running from the inside to the outer surface, the outer part was more richly innervated by immunoreactive fibers than the inner part. In the bladder dome, a moderate number of immunoreactive nerve fibers preferentially innervated the outer part of the muscle layer. In the lower bladder body, these nerve fibers increased in density in the inner part of the detrusor muscle. There was no sexual difference in density or distribution of nerve fibers. NA- and NA synthesizing enzyme-immunoreactive nerve fibers were markedly decreased in number after 6-hydroxydopamine treatment. No dopamine- or phenylethanolamine-N-methyltransferase-immunoreactive nerve fibers were present in the bladder. The findings of this study indicate that the cat bladder musculature includes longitudinal and circular muscle bundles, both of which are extensively innervated by adrenergic nerves, particularly in the outer part of the bladder.     

Ultrastructural observations of the human uterine smooth muscle cells during gestation

At term pregnancy, the myometrium consists of bundles of smooth muscle cells bound together by varying amounts of connective tissue. Each bundle contains both dark and light muscle cells. During uterine contractions it is believed that the smooth muscle cells become darker, decrease in volume, and exhibit changes in diameter. This is accompanied by widening of the interspaces and by a decrease in the areas of cellular contact. Between contractions, there are more light cells which become arranged closer to each other and exhibit large areas of interdigitation. The significance of these observations in the mechanism of uterine contraction and retraction is discussed. Cell believed to be modified smooth muscle cells occupy the myoendometrial junction and the decidua basalis. They are irregular in shape, poor in myofilament content, and rich in other cytoplasmic organelles and form a loosely arranged layer of cells between the myometrium and the trophoblast. The possible functional significance of these cells is also discussed.     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.     

An analysis of the capillary forces in liquid-phase sintering of spherical particles

The interparticle force due to capillary action of a liquid contact between two solid spheres is shown rigorously to have two contributions, one the surface tension force itself and the other due to the pressure difference caused by surface curvature. Numerical means are used to solve for the shape of the liquid surface and to evaluate this interparticle force as a function of contact angle, volume of liquid, size of sphere, and surface tension. The rigorous solution is then compared to the often-used circle approximation. We also evaluate the effect of neglecting one of the terms in the force equation, as is sometimes done in the literature. The general force relations are then used to draw several practical conclusions concerning liquid-phase sintering of spherical powders.     

Structure-function correlations in the human medial rectus extraocular muscle pulleys

PURPOSE: Fibroelastic pulleys function like the trochlea to fix the position and pulling direction of the recti extraocular muscles within the orbit. This study characterized the fine structure of the human medial rectus muscle pulley. METHODS: Human medial rectus muscle pulley tissue was dissected at autopsy, immersed in aldehyde fixative solution, and processed for and examined with light and electron microscopy. RESULTS: Pulley structure were located within posterior Tenon's fascia, closely surrounding the medial rectus muscle. Pulleys were comprised of a dense collagen matrix with alternating bands of collagen fibers precisely arranged at right angles to one another. This three-dimensional organization most likely confers high tensile strength to the pulley. Elastin fibrils were interspersed in the collagen matrix. Fibroblasts and mast cells were scattered throughout the relatively acellular and avascular collagen latticework. Connective tissue and smooth muscle bundles suspended the pulley from the periorbita. Smooth muscle was distributed in small, discrete bundles attached deeply into the dense pulley tissue. CONCLUSIONS: Fine structural observations confirm the existence and substantial structure of a pulley system in association with the medial rectus extraocular muscle. The presence of pulleys must be considered in models of the oculomotor plant. The cytoarchitecture and placement of pulleys suggest that they are internally rigid structures and are consistent with the idea that they determine functional origins for the extraocular muscles. However, the nature of the connective tissue-smooth muscle struts suspending the pulley system to the orbit supports the notion that the pulley position, and thus the vector force of the eye muscles, may be adjustable.     

Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.