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One crucial buy 10mg metoclopramide fast delivery, additional role for MAO appears to be the NORADRENALINE 177 regulation of the intraneuronal stores of noradrenaline metoclopramide 10 mg with amex. Its predominantly intraneur- onal location would suggest that its primary function is to ensure that there is always a low concentration of cytoplasmic noradrenaline buy metoclopramide 10 mg cheap. What can happen when the concentration of cytosplasmic noradrenaline is increased is illustrated by amphetamine 10mg metoclopramide amex. This drug causes a rise in the cytoplasmic noradrenaline and results in increased binding of this transmitter to the cytoplasmic side of the transporter which then carries it out of the neuron cheap 10mg metoclopramide with mastercard. By maintaining low concentrations of cytoplasmic noradrenaline, MAO will also regulate the vesicular (releasable) pool of transmitter. When this enzyme is inhibited, the amount of noradrenaline held in the vesicles is greatly increased and there is an increase in transmitter release. It is this action which is thought to underlie the therapeutic effects of an important group of antidepressant drugs, the MAO inhibitors (MAOIs) which are discussed in Chapter 20. Because of their lack of selectivity and their irreversible inhibition of MAO, the first MAOIs to be developed presented a high risk of adverse interactions with dietary tyramine (see Chapter 20). However, more recently, drugs which are selective for and, more importantly, reversible inhibitors of MAO-A (RIMAs) have been developed (e. These drugs are proving to be highly effective antidepressants which avoid the need for a tyramine-free diet. Further interest in MAO has been aroused as a result of recent research on drugs with an imidazole or imidazoline nucleus (Fig. Although many of these compounds are potent and selective a2-adrenoceptor ligands (e. It is now known that many of these drugs have their own binding sites that are now classified as imidazoline (I-) receptors. One of these, the so-called I2-receptor, has been found on MAO-B but there is general agreement that the I2-receptor is not the same as the catalytic site on the MAO enzyme. Instead, it is thought that the I2-receptor is an allosteric modulator of the catalytic site on MAO which, when activated, reduces enzyme activity. There is also some evidence for subtypes of COMT but this has not yet been exploited pharmacologically. Certainly, the majority of COMT is found as soluble enzyme in the cell cytosol but a small proportion of neuronal enzyme appears to be membrane bound. The functional distinction between these different sources of COMT is unknown. NORADRENERGIC RECEPTORS The division of adrenoceptors into a-andb-types emerged some 50 years ago and was based on the relative potencies of catecholamines in evoking responses in different peripheral tissues. Further subdivision of b-adrenoceptors followed characterisation of their distinctive actions in the heart (b1), where they enhance the rate and force of myocardial contraction and in the bronchi (b2), where they cause relaxation of smooth muscle. The binding profile of selective agonists and antagonists was the next criterion for classifying different adrenoceptors and this approach is now complemented by molecular biology. The development of receptor-selective ligands has culminated in the characterisation of three major families of adrenoceptors (a1, a2 and b), each with their own subtypes (Fig. All these receptors have been cloned and belong to the superfamily of G-protein-coupled receptors predicted to have seven transmembrane domains (Hieble, Bondinell and Ruffolo 1995; Docherty 1998). The a1-subgroup is broadly characterised on the basis of their high affinity for binding of the antagonist, prazosin, and low affinity for yohimbine but they seem to be activated to the same extent by catecholamines. There are at least three subtypes which for historical reasons (Hieble, Bondinell and Ruffolo 1995) are now designated a1A, a1B and a1D. An alternative classification (also based on sensitivity to prazosin) characterised two classes of receptor: a1H and a1L receptors. Whereas those classified as a1H seem to overlap with a1A, a1B and a1D receptors (and are now regarded as the same), there is no known equivalent of the a1L receptor. Although it is still tentatively afforded the status of a separate receptor, it has been suggested that it is an isoform of the a1A subtype (Docherty 1998). All a1-adrenoceptors are coupled to the Gq/11 family of G-proteins and possibly other G-proteins as well. When activated, they increase the concentration of intracellular Ca2‡ through the phospholipase C/diacyl glycerol/IP pathways (Ruffolo and Hieble 3 1994) but other routes have been suggested too. These include: direct coupling to Ca2‡ (dihydropyridine sensitive and insensitive) channels, phospholipase D, phospholipase A2, arachidonic acid release and protein kinase C.

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These two fluids The mucous membranes that line the tympanic cavity 10mg metoclopramide sale, the provide a liquid-conducting medium for the vibrations involved mastoidal air cells metoclopramide 10mg without a prescription, and the auditory tube are continuous with in hearing and the maintenance of equilibrium discount metoclopramide 10mg fast delivery. For this reason generic metoclopramide 10mg, infections that spread to The bony labyrinth is structurally and functionally divided the nose or throat may spread to the tympanic cavity and cause a into three areas: the vestibule cheap metoclopramide 10 mg free shipping, semicircular canals, and cochlea. Forcefully blowing the nose advances the The functional organs for hearing and equilibrium are located in spread of the infection. Sensory Organs © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 520 Unit 5 Integration and Coordination FIGURE 15. Vestibule Cochlea The vestibule is the central portion of the bony labyrinth. It con- The snail-shaped cochlea is coiled two and a half times around a tains the vestibular (oval) window, into which the stapes fits, and central core of bone (fig. There are three chambers in the the cochlear (round) window on the opposite end (fig. Both the utricle and sac- vestibuli and the scala tympani are filled with perilymph. They are cule contain receptors that are sensitive to gravity and linear completely separated, except at the narrow apex of the cochlea, movement (acceleration) of the head. Between the scala vestibuli and the scala tympani is Semicircular Canals the cochlear duct, the triangular middle chamber of the cochlea. The roof of the cochlear duct is called the vestibular membrane, Posterior to the vestibule are the three bony semicircular canals, and the floor is called the basilar membrane. Sensory Organs © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 15 Sensory Organs 521 FIGURE 15. Within the cochlear duct is a specialized structure called the spiral organ (organ of Corti). The sound receptors that transform mechanical vibrations into nerve impulses are located along the basilar membrane of this structure, making it the func- Hair tional unit of hearing. The epithelium of the spiral organ consists cells of supporting cells and hair cells (figs. The bases of the hair cells are anchored in the basilar membrane, and their tips are embedded in the tectorial membrane, which forms a gelatinous canopy over them. Kardon, Tissues and Organs: A Text-Atlas of Scanning Electron Microscopy. Sensory Organs © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 522 Unit 5 Integration and Coordination FIGURE 15. The scala vestibuli and the scala tympani, which contain perilymph, are continuous at the helicotrema. The cochlear duct, which con- tains endolymph, separates the scala vestibuli and the scala tympani. Sounds of low frequency (blue arrow) cause pressure waves of perilymph to pass through the helicotrema and displace the basilar membrane near its apex. Sounds of medium frequency (green arrow) cause pressure waves to displace the basilar membrane near its center. Sounds of high frequency (red arrow) cause pressure waves to displace the basilar membrane near its base. For example, striking the high C on a piano produces a high frequency of sound that has a high pitch. Pathways for Hearing The intensity, or loudness of a sound, is directly related to the amplitude of the sound waves. Sound intensity is measured Sound Waves in units known as decibels (dB). A sound that is barely audible— Sound waves travel in all directions from their source, like rip- at the threshold of hearing—has an intensity of zero decibels. These waves of energy are Every 10 decibels indicates a tenfold increase in sound intensity: characterized by their frequency and their intensity. The fre- a sound is 10 times higher than threshold at 10 dB, 100 times quency, or number of waves that pass a given point in a given higher at 20 dB, a million times higher at 60 dB, and 10 billion time, is measured in hertz (Hz). The healthy human ear can detect very related to its frequency—the higher the frequency of a sound, small differences in sound intensity—from 0. Sensory Organs © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 15 Sensory Organs 523 Thalamus Auditory cortex (temporal lobe) Inferior colliculus Medial geniculate Midbrain body of thalamus Cochlear nucleus Medulla oblongata Vestibulocochlear nerve From spiral organ (of Corti) FIGURE 15. A snore can be as loud as 70 dB, as compared with 105 dB Sounds of low pitch (with frequencies below about 50 Hz) for a power mower.

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Skeletal and cardiac muscle have repeat- derstood and many transmitter systems may be in- ing sarcomeres metoclopramide 10mg visa, but smooth muscle does not order metoclopramide 10mg line. The width of the I band changes be- ing system and convey information to the cortex order metoclopramide 10 mg line. These nuclei are critical for the maintenance of arousal The Z lines move closer together purchase 10mg metoclopramide fast delivery. Without the intralaminar nuclei generic 10 mg metoclopramide with amex, band width and the moving of the Z lines together are beta rhythms and attention would be severely compro- proportional, but there is no change in A band dimen- mised. ATP must bind to the myosin heads the reticular activating system and its input. Relaxed skeletal muscle is in a state of which does not generate language. The enzymatic activity of myosin what the object is, the information must cross to the is greatly enhanced by its interaction with actin. This crossing occurs through the cor- role of calcium is as an activator, not an inhibitor; at rest, pus callosum. The fornix and hippocampus would be the concentration of free calcium is low. Neither the primary so- ament space into the sarcoplasmic reticulum (not the matic sensory cortex on the left side nor the visual cor- extracellular space) is an absolute requirement for nor- tex on either side plays a role in identifying an object mal relaxation. A reduction of ATP would promote placed in the left hand by tactile cues. When the myofilament overlap is de- formation of long-term (declarative) memory. With- creased above the optimal length, fewer crossbridges APPENDIX A Answers to Review Questions 713 (borne on the myosin filaments) are able to interact events and will not be affected by the blocked postsy- with actin, and there is a proportionate decrease in the naptic membrane. The contraction will be twitch-like, gether as the muscle becomes thinner. The sarcoplasmic reticulum releases ditional calcium released from the SR in response to calcium rapidly and in close proximity to the myofila- the second stimulus. Calcium diffuses away from the tro- change the size of the contraction but have nothing to ponin complex because the intracellular concentration do with whether it is isometric. As long as the muscle is actually lift- Calcium does not bind to active sites on myosin mole- ing the afterload, this is the only factor that determines cules, and individual actin molecules do not have en- the force. This is a statement of relationship that that provide energy, via several routes, into the ATP is graphically represented in the force-velocity curve. They are not used directly in the crossbridge cy- Regarding choice D, note that it is force that deter- cle. This is a point at the maximum of the velops after death because the processes that generate power output curve. The forearm/biceps combination, be- bic pathways (glycolysis), the muscle keeps function- cause of the proportions involved, operates at a me- ing at the expense of generating end products that will chanical disadvantage with regard to force, trading de- eventually require oxygen consumption for their fur- creased hand force for increased hand velocity. Choice A is a possibility, but almost all mus- ability of the sarcoplasmic reticulum would leave a cles have some mixture of fiber types. The diffusion of calcium when the volume of the organ is prevented from away from the regulatory proteins would be slower, changing, as by a closed sphincter. Any shortening of and crossbridges would detach less rapidly; conse- smooth muscle in a hollow organ would be against quently, the muscle would relax more slowly. Both sodium and potassium pass through myosin-based regulation in smooth muscle. Choice A it simultaneously down their respective electro- represents the skeletal muscle condition, while choices chemical gradients. The endplate potential and the action in particular, choice D is the reverse of the truth. While smooth and skeletal muscle but the postsynaptic channels in the endplate region can exert about the same amount of force per cross- are not voltage-sensitive. This means that the endplate sectional area, smooth muscle does it much more eco- potential cannot regenerate and be propagated. It is capable of extreme shortening when cause the channels do not select between sodium and conditions external to the muscle allow. The crossbridge cycle of smooth such, it can never assume a large inside-positive value.

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J Trauma 24:448-451 Arthroscopy 9:17-21 Erickson SJ purchase metoclopramide 10mg with amex, Fitzgerald SW buy generic metoclopramide 10 mg on-line, Quinn SF buy metoclopramide 10mg visa, Carrera GF discount 10 mg metoclopramide with mastercard, Black KP generic 10 mg metoclopramide with amex, Parsonage MJ, Turner JWA (1948) Neuralgic amyotrophy. The Lawson TL (1992) Long bicipital tendon of the shoulder: nor- shoulder-girdle syndrome. Radiol Clin N Am; 235-249 New York, 29-53 Fleckenstein JL, Watumull D, Conner KE et al (1993) Denervated Rokito AS, Bilgen OF, Zuckerman JD, Cuomo F (1996) Medial human skeletal muscle: MR imaging evaluation. Am J Orthop 25:314, 318-323 Greenan TJ, Zlatkin MB, Dalinka MK, Estehai JL (1993) Shanley DJ, Mulligan ME (1990) Osteochondrosis dissecans of the Posttraumatic changes in the posterior glenoid and labrum in glenoid. MacGraw-Hill, New York, 1994, Fritz RC, Helms CA, Steinbach LS, Genant HK. Tirman PF, Feller JF, Janzen DL, Peterfy CG, Bergman AG (1994) Radiology 182:437-444 Association of glenoid labral cysts with labral tears and gleno- Helms CA, Martinez S, Speer KP (1999) Acute brachial neuritis humeral instability: radiologic findings and clinical signifi- (Parsonage-Turner syndrome): MR imaging appearance-report cance. Radiology 207:255-259 Tuckman GA (1994) Abnormalities of the long head of the biceps Jee WH, McCauley TR, Katz LD, Matheny JM, Ruwe PA, tendon of the shoulder: MR imaging findings. Am J Daigneault JP (2001) Superior labral anterior posterior Roentgenol 163:1183-1188 (SLAP) lesions of the glenoid labrum: reliability and accura- Uetani M, Kuniaki H, Matsunaga N, Imamura K, Ito N (1983) cy of MR arthrography for diagnosis. Radiology 189:511- Kramer J, Recht M, Deely DM, Schweitzer M, Pathria MN et al 515 (1993) MR appearance of idiopathic synovial osteochondro- Walch G, Nove-Josserand L, Boileau P, Levigne C (1998) matosis. J Comput Assist Tomogr 17:772-776 Subluxations and dislocations of the tendon of the long head Lin J, Jacobson JA, Jamadar DA, Ellis JH (1999) Pigmented vil- of the biceps. J Shoulder Elbow Surg 7:100-108 lonodular synovitis and related lesions: the spectrum of imag- Yu JS, Greenway G, Resnick D (1998) Osteochondral defect of the ing findings. Am J Roentgenol 172:191-197 glenoid fossa: Cross-sectional imaging features. Radiology Linker CS, Helms CA, Fritz RC (1993) Quadrilateral space syn- 206:35-40 drome: evaluation of median nerve circulation with dynamic Zanetti M, Weishaupt D, Jost B, Gerber C, Hodler J (1999) MR contrast-enhanced MR imaging. Radiology 188:675-676 imaging for traumatic tears of the rotator cuff: High prevalence McCarty DJ, Halverson PB, Carrera GF et al (1981) “Milwaukee of greater tuberosity fractures and subscapularis tendon tears. Steinbach2 1 University of California, San Diego, and VAHCS, CA, USA 2 Musculoskeletal Imaging, University of California San Francisco, San Francisco, CA, USA Elbow injuries are common, especially in the athlete, and impaction and shearing forces applied to the articular sur- can be basically classified into acute or chronic injuries. The overall configuration of the humeroradial ar- The following discussion of magnetic resonance imaging ticulation, in this case, can be likened to a mortar and (MRI) of the elbow will address variations in normal pestle, with the capitellar articular surface impacting that anatomy that represent pitfalls in imaging diagnosis, and of the radius to result in a chondral or osteochondral le- commonly encountered osseous and soft-tissue pathology. These acute post-traumatic lesions are manifested on MRI as irregularity of the chondral surface, disruption or irregularity of the sub- Osseous Anatomic Considerations and Pathology chondral bone plate, and or the presence of a fracture line. The acuity of the lesion and a post-traumatic etiolo- The lateral articulating surface of the humerus is formed gy are implied by the presence of marrow edema and by the capitellum, a smooth, rounded prominence that joint effusion. Close inspection of the location of the le- arises from its anterior and inferior surfaces. As it does sion on coronal and sagittal MRI is of the utmost impor- so, its width decreases from anterior to posterior. This tance in order to distinguish a true osteochondral lesion morphology of the capitellum (smooth surface), in con- from the pseudodefect of the capitellum. Correlation with junction with the knowledge that the adjacent lateral epi- presenting clinical history is also helpful in determining condyle (rough surface) is a posteriorly oriented osseous the etiology of imaging findings. Osteochondritis dissecans is thought the configuration of a figure of eight. At the waist of the to occur in immature athletes between 11 and 15 years of eight, or junction between anterior and posterior aspects age, rarely in adults. Osteochondritis dissecans of the of the ulna, the articular surface is traversed by a carti- elbow involves primarily the capitellum, but reports have lage-free bony ridge. This trochlear ridge is 2 to 3 mm described this process in the radius and trochlea. It should not be mistaken for a central os- the role of imaging is to provide information regarding the teophyte. The waist of the figure of eight is formed by the integrity of the overlying articular cartilage, the viability tapered central surfaces of the coronoid and olecranon of the separated fragment, and the presence of associated processes both medially and laterally, forming small cor- intra-articular bodies. On sagittal MRI, these and MRI with and without arthrography can provide this focal regions devoid of cartilage could be mistaken for a information to varying degrees, although no scientific in- focal chondral lesion. MRI, with its excellent Osteochondral Lesions soft-tissue contrast, allows direct visualization of the ar- ticular cartilage, as well as of the character of the interface In the case of acute medial elbow injury, the involvement of the osteochondral lesion with native bone (Fig. The of a valgus force is usually described as one of the most presence of joint fluid or granulation tissue at this inter- common mechanisms of injury. Subchondral bone face, manifested as increased signal intensity on fluid-sen- and cartilage injuries that occur in this setting result from sitive MRI, generally indicates an unstable lesion.

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