By O. Kalan. Barton College.
Finally generic 800mg cialis black with amex, an unusual feature of these receptors is that they are downregulated by prolonged exposure to antagonists buy 800 mg cialis black overnight delivery, as well as agonists. The reason for this is uncertain but it could suggest that drugs which hitherto have been regarded as antagonists are, in fact, inverse agonists. However, little is known about these receptors, mainly because of the shortage, until recently, of selective ligands, their low density and the limited distribution of their mRNA in the brain. However, as information accrued from cloning studies, pharmacological characterisation, and discovery of its second messenger system, it became evident that this receptor shared the characteristics of the 5-HT2 receptor family, rather than those of a 5-HT1 receptor. The switch in classification from a 5-HT1C to a 5-HT2C receptor explains the gap in the 5-HT1 receptor family. The 5-HT2C receptor was first found in the choroid plexus, where it is thought to regulate the formation of CSF, but it has since been found in cortical and limbic areas as well as the basal ganglia. In the choroid plexus, at least, its actions seem to be mediated by activation of phospholipase C with a resulting depolarisation of the host cell. Like the 5-HT2A subtype, 5-HT2C receptors are downregulated by prolonged exposure to antagonists (inverse agonists? The discovery that 5-HT2C receptor mRNA is subject to posttranslational changes suggests that there could be several different isoforms of this receptor and it cannot be assumed that they are functionally the same. As far as can be certain, given the lack of selective ligands, their activation elsewhere in the brain is thought to culminate in reduced locomotor activity and hyperthermia. However, interest in these receptors as possible therapeutic targets is fostered by evidence that their agonists, such as mCPP, appear to be profoundly anxiogenic (see Chapter 19) and reduce food intake (see below). Instead, they comprise a pentameric complex of subunits that incorporates an ion channel. This is selective for the cations Na and K which, when opened, leads to depolarisation of the host cell. However, they are also found elsewhere in lower concentrations, notably in the cortex, amygdala and hippocampus, where they are thought to be associated mainly with GABAergic neurons. Interestingly, their function is modified by many agents that allosterically modify GABAA receptor function (e. A further parallel with the GABAA receptor is that there could well be differences in subunit composition of 5-HT3 receptors such that different heteromeric complexes form receptors which are functionally distinct. These receptors are best known for their stimulation of dopamine release. Indeed, it is attenuation of dopamine release in the area postrema by the 5-HT3 receptor antagonist, ondansetron, that is thought to explain its anti-emetic effects. However, they are also thought to influence release of other neurotransmitters including GABA, acetylcholine and noradrenaline; they are even thought to increase somatodendritic release of 5-HT in the Raphe nuclei. So far, despite vigorous attempts to find other clinical applications for ondansetron, none has proved convincing. So far, the literature on its behavioural effects is somewhat inconsistent but agonists of this receptor are being explored as possible cognitive enhancers. However, studies using antibodies generated against these receptors have shown that they are present on glial cells and investigations of cloned receptors suggest that they are negatively coupled to Gi/o proteins and reduce activation of adenylyl cyclase In contrast, the 5-ht6 receptor is positively coupled to Gs proteins and increases adenylyl cyclase activity. Again, the native 5-ht6 receptor has not been characterised but in situ hybridisation suggests that its mRNA is present in the amygdala, nucleus accumbens, striatum, cortex and olfactory tubercle. Many antipsychotic agents and some antidepressant drugs show high-affinity binding to this receptor where they act as antagonists but it remains to be seen whether this contributes to their therapeutic profile. The recent development of selective antagonists for 5-ht6 receptors could help to answer this question but, so far, the most promising findings are that their antagonists increase seizure threshold and could turn out to be beneficial in the treatment of epilepsy. However, at least three splice variants are expressed in human tissue and the impact of these different isoforms on the function of these receptors is not known. Radioligand binding and the distribution of 5-HT7 receptor mRNA suggest that the density of these receptors is high in the thalamus, hippocampus and hypothalamus where (in the suprachiasmatic nucleus) they are thought to synchronise circadian rhythms with the light cycle (see Chapter 22). It is obvious that strenuous efforts have been invested in the research of 5-HT receptors and, in particular, in the development of receptor-selective agonists and antagonists. A further ambition is that, by avoiding activation of other 5-HT receptors, the risk of any unwanted side-effects would be eliminated. Of course, it is equally possible that reduction in non-specific receptor interactions could actually unmask some side-effects. Also, the benefits of the 5-HT3 antagonist, ondansetron, in relieving nausea, with minimal side-effects, are undisputed. However, in other respects, this approach to drug development has been disappointing. This is probably because all the 5-HT receptors have a wide and overlapping distribution in the brain and it would be naive to suppose that any physiological response relies exclusively on the activation of any single 5-HT receptor. What the overall physiological consequences of either an increase or decrease in 5-HT transmission in any brain region might be is beyond the scope of this chapter. However, it is certain that the diverse cocktail of 5-HT receptors in every brain region gives scope for flexibility and refinement in the 5-HT response that would not be possible if there were only the two receptors identified by Gaddum. This flexibility applies not only to the qualitative features of the response but also its duration. Another dimension of sophistication is added by the different affinities of 5-HT for each of its receptors and differences in their rates of desensitisation. An interesting discussion of how all these variables could affect overall 5-HT transmission in the brain can be found in Uphouse (1997).
Radiographics 19:1253-1280 joint synovitis: gray-scale and power Doppler US quantifica- 55 best cialis black 800mg. Giovagnorio F purchase cialis black 800 mg without a prescription, Andreoli C, De Cicco ML (1997) Ultrasono- dons: clinical relevance of neovascularisation diagnosed with graphic evaluation of de Quervain’s disease. Serafini G, Derchi LE, Quadri P et al (1996) High resolution Ankle US: technique, anatomy and pathology. Buchberger W, Judmaier W, Birbamer G et al (1992) Carpal fluid in the hindfoot and ankle: detection of amount and dis- tunnel syndrome: diagnosis with high-resolution sonography. Bianchi S, Abdelwahab IF, Zwass A et al (1993) Sonographic Achilles tendon tears: sonographic accuracy and characterization findings in examination of digital ganglia: retrospective study. Van Holsbeeck MT, Eyler WR, Suerman LS et al (1994) De Schepper AM (ed) Imaging of soft tissue tumors. Springer- Detection of infection in loosened hip prosthesis: eficacy of Verlag, Heidelberg, pp 3-18 sonography. Morvan G (2001) Les bursopathies de la racine du ankle tendon impingement with surgical correlation. In: Rodineau J, Saillant G: Actualités sur les 179:949-953 tendinopathies et les bursopathies du membre inférieur. Ortega R, Fessell D, Jacobson J et al (2002) Sonography of an- Masson, Paris, 27-36 kle ganglia with pathologic correlation in 10 pediatric and 39. Connell D, Bass C, Sykes C et al (2003) Sonographic evalua- adult patients. Pollak RA, Bellacosa RA, Dornbluth NC et al (1992) 13:1339-1347 Sonographic analysis of Morton’s neuroma. Pelsser V, Cardinal E, Hobden R et al (2001) Extraarticular 31:534-537 snapping hip: sonographic findings AJR 176:67-73 64. Cardinal E, Bureau N, Lafortune M et al (2002) The streak ar- Morton’s neuromas. AJR 174:1723-1728 tifact using tissue harmonic imaging: a new sign of snapping 65. Griffith J, Wong T, Wong S et al (2002) Sonography of plantar Radiological anatomy of the groin region Eur Radiol 10:661- fibromatosis. Harcke HT (1995) The role of ultrasound in diagnosis and bodies in soft tissue: Detection at US. Radiology 206:45-48 PEDIATRIC SATELLITE COURSE “KANGAROO” IDKD 2005 The Spectrum of Non-accidental Injury and Its Imitators in Children* P. Kleinman Department of Radiology, Children’s Hospital, Boston, MA, USA Introduction. In recent years, increasing attention has been given to those conditions that may simulate inflicted injury. A Skeletal injuries are the most common findings noted on variety of normal variants, naturally occurring diseases, imaging studies in cases of child abuse. In infants, they and accidental skeletal injuries may be confused with the result from shaking and other forms of manual assault findings of child abuse. In contrast to central nervous system and other with the defense against allegations of abuse are often visceral injuries, they are rarely life threatening. It is therefore essential that diagnostic imaging spe- tral to the diagnosis of abuse. In infants, certain lesions cialists involved with cases of alleged abuse conduct their are sufficiently characteristic to point strongly to the di- studies in a thorough and conscientious fashion that will agnosis of inflicted trauma (Table 1). Other fractures are provide the greatest likelihood of a correct diagnosis that less specific for abuse, but when correlated with other can be sustained in a highly adversarial legal arena. In the 50 years since Caffey’s original description, ra- Classic Metaphyseal Lesion diologists have become familiar with the imaging fea- tures of commonly encountered inflicted skeletal injuries The corner fracture and bucket handle lesions de- scribed in 1957 by Caffey are frequent findings in young abused infants. Specificity of radiologic findings (From with permission) by assailants. Repro- duced with permis- High specificitya sion from) Classic metaphyseal lesions Rib fractures, especially posterior Scapular fractures Spinous process fractures Sternal fractures Moderate specificity Multiple fractures, especially bilateral Fractures of different ages Epiphyseal separations Vertebral body fractures and subluxations Digital fractures Complex skull fractures Common but low specificity Subperiosteal new bone formation Clavicular fractures Long bone shaft fractures * This chapter originally appeared in: von Schulthess GK, Zolli- Linear skull fractures kofer Ch L (2001) Musculoskeletal Diseases - Diagnostic Imaging and Interventional Techniques. Springer-Verlag Italia, Milan a Highest specificity applies in infants 170 P. Kleinman extends in a planar fashion through the primary spon- fracture may extend partially or completely across the giosa. The fractures are most common in seous junction, and peripherally, the fracture veers the distal femur, proximal and distal tibia, and proxi- from the physis to undercut a larger peripheral seg- mal humeri and are much less common at the elbow, ment encompassing the subperiosteal bone collar. Corner fracture and bucket-handle patterns of the classic b metaphyseal lesion (CML). Fractures (arrows) extend adjacent to the chondroosseous junction and then veer toward the diaphysis to under- cut the large peripheral segment that encompasses the subperiosteal bone collar. The frac- tures may also occur with the sudden acceleration and Most cases of osteogenesis imperfecta are accompa- deceleration of the extremities as the infant is shaken nied by blue sclera, frank bony demineralization and violently while grabbed by the thorax. When present in other typical clinical and radiologic features (Type I). However, a variety of bone fractures involve the shafts or metadiaphyseal differential considerations for the classic metaphyseal regions. The presence of demineralization Rickets and other radiologic features of osteogenesis imper- fecta confirm the diagnosis. Paterson and colleagues Metaphyseal irregularity, cupping, physeal widening and have described a group of children with metaphyseal bony demineralization are the hallmarks of rickets, how- lesions as well as other osseous injuries characteristic ever, on occasion discrete osseous fragments resembling of abuse. They coined the term “temporary brittle corner fractures may be identified in the absence of more bone disease” to explain these injuries.
Which of the following sets of attrib- (A) The cycle involves only isometric muscle shortens utes best characterizes cardiac muscle? The factor common to most changes in (A) Large cells buy 800mg cialis black with amex, electrically isolated buy 800 mg cialis black visa, (B) Isometric relaxation occurs at a cardiac muscle contractility is the neurally stimulated shorter length than isometric (A) Amplitude of the action potential (B) Small cells, electrically coupled, contraction (B) Availability of cellular ATP chemically stimulated (C) The muscle relaxes along the same (C) Cytoplasmic calcium (C) Small cells, electrically coupled, combination of lengths and forces that concentration spontaneously active it took during contraction (D) Rate of neural stimulation (D) Small cells, electrically isolated, (D) The complete cycle in cardiac 10. At a given muscle length, the velocity spontaneously active muscle is isotonic of contraction depends on 2. What is the physiological role of the (A) Only the afterload electrical and a mechanical syncytium. The regulation of contraction in preload SUGGESTED READING cardiac muscle is (D) It prevents a contraction from American Heart Association. Website: (A) Most like that of smooth muscle having an isometric phase at shorter http://www. Why does cardiac muscle shorten less Mechanisms of Contraction of the (i. Boston: Lit- (C) Independent of filament-related (A) Higher loads cause a reduction in tle, Brown, 1976. New York: McGraw-Hill, stimulation (B) Higher loads cause rapid fatigue, 1981. Carmel, IN: Biological Sci- (A) The rate of neural stimulation is premature relaxation ences Press-Cooper Group, 2000. Oxford: Oxford University potential lasts into the relaxation phase important limit to force production in Press, 1979. CASE STUDIES FOR PART III • • • CASE STUDY FOR CHAPTER 8 four limbs, but the woman does not complain of muscu- lar soreness. She is somewhat underweight, slightly Polymyositis in an Older Patient short of breath, and speaks in a low voice. Laboratory A 67-year-old woman consulted her physician because of tests show a moderately elevated creatine kinase level. She reported There is no family history of muscle problems, and she is difficulty in rising out of a chair and had intermittent diffi- not currently taking any medication. Physical examination reveals the Because of the symptoms present, no muscle biopsy presence of a light purple rash around her eyes and on or electromyographic study is carried out. Muscle weakness is noted in all agnosis of polymyositis/dermatomyositis was made. The (continued) 188 PART III MUSCLE PHYSIOLOGY woman is placed on high-dose prednisone, and arrange- steroidal drug to manage the pain and inflammation and ments are made for periodic tests for circulating muscle is told to lessen the pain by applying ice packs to the af- enzymes. He is advised to avoid stair climbing as specialist to screen for a possible underlying malig- much as possible during this time, but to begin walking nancy, and physical therapy is strongly recommended. On a fol- In follow-up visits, the woman shows gradual im- low-up visit 2 weeks later, he is experiencing little im- provement in muscle strength, and her rash is much less pairment in walking, although the strength of the leg is apparent. She maintains a still less than normal and stair climbing is still somewhat regimen of physical therapy and is able to have the pred- of a problem. He is advised to return to regular activity, nisone dosage progressively reduced over the course of but to avoid any undue overloading of the affected leg the next year. Could the shortness of breath also have been a result of pose a special risk for injury? Does the pattern of recovery suggest that the diagnosis was this injury? Why was the patient given a limited supply of the pain med- life threatening. Although several things could contribute to shortness of Answers to Case Study Questions for Chapter 9 breath, weakness of the respiratory muscles can lead to hy- 1. The muscle was undergoing an eccentric contraction; that poventilation; this, too, can be life threatening. The response to therapy was what one would expect for a landing, and the body weight extended it while it was ac- person suffering from polymyositis. Such a stretch can produce a force considerably in ex- muscular dystrophy would not have responded as well to cess of the maximal isometric capability of a muscle. Second, because the patient was not accustomed to sidered, like most cases of polymyositis, to be of idiopathic the activity in question, the muscle was not conditioned to origin. Third, the height from References which the patient jumped could potentially generate a force Dalakas MC, ed. The pain was localized in the general area of the myotendi- Maddison PJ, et al. Given the same conditions, a similar jump to the one caus- ing the injury would be quite likely to result in reinjury. In CASE STUDY FOR CHAPTER 9 general, any activity that would lead to an eccentric contrac- A Muscle-Pull Injury tion of the muscle would put it at risk. This would explain A 35-year-old man visited his family physician early on a the caution against stair climbing during the early stages of Monday morning. There should be a gradual return to full activity, with ade- vious discomfort. When he arose from the waiting-room quate time for healing and repair, without any sudden in- chair, it was with some difficulty and with considerable crease in the use of the muscle. The initial precipitating be- assistance from his arms and his left leg. The use of the anti-inflammatory medication should be lim- backyard tree for his children. At one point during the ited because its continued use has been shown to delay the work, he jumped to the ground from a ladder leaning healing process, and it could also mask warning signs of against the tree, a distance of about 4 feet. Clin Sports Med considerable discomfort, and the pain did not lessen 1997;16:419–434.
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