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Phagocytes bear several different receptors that recognize microbial components and induce phagocytosis cholesterol ratio levels uk cheap ezetimibe 10 mg otc. Upon phagocytosis cholesterol foods to avoid chart ezetimibe 10 mg for sale, macrophages and neutrophils also produce a variety of other toxic products that help kill the engulfed microorganism high density cholesterol foods order 10 mg ezetimibe amex. Neutrophils are short-lived cells, dying soon after they have accomplished a round of phagocytosis. Dead and dying neutrophils are a major component of the pus that forms in some infections; bacteria that give rise to such infections are thus known as pyogenic bacteria. Macrophages, on the other hand, are long-lived and continue to generate new lysosomes. People with this defect are unusually susceptible to bacterial and fungal infections, especially in infancy. Bactericidal agents produced or released by phagocytes on the ingestion of microorganisms. Some of them are toxic; others, such as lactoferrin, work by binding essential nutrients and preventing their uptake by the bacteria. The same substances can be released by phagocytes interacting with large antibody-coated surfaces such as parasitic worms or host tissues. As these agents are also toxic to host cells, phagocyte activation can cause extensive tissue damage during an infection. Macrophages can make this response immediately on encountering an infecting microorganism and this can be sufficient to prevent an infection from becoming established. The great cellular immunologist Elie Metchnikoff believed that the innate response of macrophages encompassed all host defense and, indeed, it is now clear that invertebrates, such as the sea star that he was studying, rely entirely on innate immunity for their defense against infection. Although this is not the case in humans and other vertebrates, the innate response of macrophages still provides an important front line of host defense that must be overcome if a microorganism is to establish an infection that can be passed on to a new host. A key feature that distinguishes pathogenic from nonpathogenic micro-organisms is their ability to overcome innate immune defenses. Pathogens have developed a variety of strategies to avoid being immediately destroyed by macrophages. Many extracellular pathogenic bacteria coat themselves with a thick polysaccharide capsule that is not recognized by any phagocyte receptor. Other pathogens, for example mycobacteria, have evolved ways to grow inside macrophage phagosomes by inhibiting fusion with a lysosome. Without such devices, a microorganism must enter the body in sufficient numbers to simply overwhelm the immediate innate host defenses and establish a focus of infection. The second important effect of the interaction between pathogens and tissue macrophages is activation of macrophages to release cytokines and other mediators that set up a state of inflammation in the tissue and bring neutrophils and plasma proteins to the site of infection. Receptors that signal the presence of pathogens and induce cytokines also have another important role. This is to induce the expression of so-called co-stimulatory molecules on both macrophages and dendritic cells, another type of phagocytic cell present in tissues, thus enabling these cells to initiate an adaptive immune response (see Section 16). The cytokines released by macrophages make an important contribution both to local inflammation and to other induced but nonadaptive responses that occur in the first few days of a new infection. We will be describing the role of individual cytokines in these induced responses in the last part of this chapter. However, since an inflammatory response is usually initiated within minutes of infection or wounding, we will outline here how it occurs and how it contributes to host defense. The first is to deliver additional effector molecules and cells to sites of infection to augment the killing of invading microorganisms by the front-line macrophages. The second is to provide a physical barrier preventing the spread of infection, and the third is to promote the repair of injured tissue, a nonimmunological role that we will not discuss further. Inflammation at the site of infection is initiated by the response of macrophages to pathogens. Inflammatory responses are operationally characterized by pain, redness, heat, and swelling at the site of an infection, reflecting three types of change in the local blood vessels. The first is an increase in vascular diameter, leading to increased local blood flow hence the heat and redness and a reduction in the velocity of blood flow, especially along the surfaces of small blood vessels. The second change is that the endothelial cells lining the blood vessel are activated to express adhesion molecules that promote the binding of circulating leukocytes. The combination of slowed blood flow and induced adhesion molecules allows leukocytes to attach to the endothelium and migrate into the tissues, a process known as extravasation, which we will describe in detail later. All these changes are initiated by the cytokines produced by activated macrophages. Once inflammation has begun, the first cells attracted to the site of infection are generally neutrophils. In the later stages of inflammation, other leukocytes such as eosinophils and lymphocytes also enter the infected site. The third major change in the local blood vessels is an increase in vascular permeability. Instead of being tightly joined together, the endothelial cells lining the blood vessel walls become separated, leading to exit of fluid and proteins from the blood and their local accumulation in the tissue. This accounts for the swelling, or edema, and pain as well as the accumulation of plasma proteins that aid in host defense. These changes are induced by a variety of inflammatory mediators released as a consequence of the recognition of pathogens. Their actions are followed by those of the cytokines and chemokines (chemoattractant cytokines) that are synthesized and secreted by macrophages in response to pathogens. As we will see in the next part of the chapter, another way in which pathogen recognition rapidly triggers an inflammatory response is through activation of the complement cascade. If wounding has occurred, the injury to blood vessels immediately triggers two other protective enzyme cascades. The kinin system is an enzymatic cascade of plasma proteins that is triggered by tissue damage to produce several inflammatory mediators, including the vasoactive peptide bradykinin. This causes an increase in vascular permeability that promotes the influx of plasma proteins to the site of tissue injury. It also causes pain, which, although unpleasant to the victim, draws attention to the problem and leads to immobilization of the affected part of the body, which helps to limit the spread of any infectious agents. The coagulation system is another enzymatic cascade of plasma enzymes that is triggered following damage to blood vessels. This leads to the formation of a clot, which prevents any microorganisms from entering the bloodstream. Both these cascades have an important role in the inflammatory response to pathogens even if wounding or gross tissue injury has not occurred, as they are also triggered by endothelial cell activation. Thus, within minutes of the penetration of tissues by a pathogen, the inflammatory response causes an influx of proteins and cells that will control the infection. It also forms a physical barrier to limit the spread of infection and makes the host fully aware of what is going on. The mammalian body is susceptible to infection by many pathogens, which must first make contact with the host and then establish a focus of infection in order to cause disease.
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Will cardiovascular medicine lose its soul by forsaking the primacy of the physical examination cholesterol ratio calculator nz purchase ezetimibe 10 mg line, or will we enhance our ability to cholesterol lowering foods and supplements discount ezetimibe generic help patients through examination that cholesterol definition biology buy online ezetimibe, in the right hands, promises prompt and accurate evaluations? First, whatever their specialty, training, or background, those who wish to add acquisition and/or interpretation of echocardiograms to their skill set can benefit remarkably from this clear and readable text. Second, by integrating echocardiography into the physiological tradition of cardiovascular medicine, Solomon and colleagues provide a firm foundation for those who wish to supplement the complete and careful physical examination by the aware practitioner with state-of-the-art information available from the latest technological advances in noninvasive diagnosis. Despite the existence of other methods to image the heart, such as nuclear imaging, angiography, cardiac magnetic resonance, and cardiac computed tomography, echocardiography continues to be the "bread and butter" imaging modality of cardiologists worldwide. Echocardiography has become so central to our care of patients precisely because it is almost universally available, can be performed in the outpatient setting or the intensive care unit, provides usable clinical information on the vast majority of patients, is relatively inexpensive, and has significant clinical and prognostic value. Although most previous echocardiography books have been designed either for physicians-generally cardiologists-or cardiac sonographers, the basic principles of echocardiography are the same regardless of the learner. Indeed, sonographers are often the first to make an important diagnosis; conversely, in many institutions, physicians, not sonographers, perform echocardiographic scans. Echocardiography is the perfect marriage between anatomy and physiology, and an essential understanding of both is required of the echocardiographer. A substantial amount of this text is dedicated to the underlying physical and physiological principles. The principles discussed in the text will be reinforced by the abundant echocardiographic images and dedicated illustrations demonstrating relevant cardiac anatomy and physiology. Our experience teaching echocardiography to fellows suggests that it can be difficult to learn a dynamic imaging modality such as echocardiography from static images. Even as we embrace other emerging cardiac imaging technologies, advances in ultrasound technology in general and cardiac ultrasound in particular are leading to continued improvements in image quality and new techniques and applications of cardiac ultrasound. These advances will ensure that echocardiography will continue to remain the leading cardiac imaging modality for some time to come. Solomon, and Rajesh Janardhanan Echocardiographic Assessment of Diastolic Function. Bermudez Adult Congenital Heart Disease in General Echocardiography Practice: An Introduction. The individual video clips are cited in the text along with the figure to which they correspond by number. The image files are organized into folders by chapter number and are viewable in most Web browsers. The number following "f" at the end of the file name identifies the corresponding figure in the text. The basic principles of echocardiography, including the mechanical features of echocardiographic equipment, are no different from diagnostic ultrasound in general. Nevertheless, there are aspects of echocardiography that set it apart from general ultrasonography. Because the heart is a moving organ, and because echocardiography must additionally capture that movement, an understanding of echocardiography requires an understanding of both cardiac anatomy and physiology. This chapter reviews the basic principles of echocardiography and serves as a basis for understanding the specific disease processes discussed in the remainder of this text. Frequency and wavelength are inversely related, but this relationship is dependent on the propagation velocity (speed) of ultrasound. Sound waves traverse different media-water, tissue, air, bone-at different speeds. The following equation defines the relationship between frequency, wavelength, and propagation velocity: c=. This relationship is important because the resolution of ultrasound-the ability to discern small structures-is dependent on the wavelength; the shorter the wavelength, the higher the resolution. Sound frequency is measured in hertz (cycles per second); humans can hear sounds between 20 and 20,000 Hz. From that transit time, the machine can calculate the depth within the body of the reflecting structure(s). This information can be used to generate a scanline in which reflecting structures are depicted on a screen along the scanline based on the distance from the transducer and the amplitude of the reflected waves. Early ultrasound machines utilized a single directional beam of ultrasound that was manually directed toward different reflecting structures; this technique is called "M-Mode" echocardiography and is still used today. In M-Mode echocardiography, the resulting scanline is displayed along a moving paper sheet (or on a screen) so that time is recorded on the x-axis and distance from the transducer on the y-axis. The amplitude of the reflection is recorded as the intensity of an individual point along the scanline. M-mode echocardiography is utilized as part of the standard echocardiographic examination (see Chapters 2 and 3). Modern ultrasound machines utilize multiple scanlines (up to 512) to generate a two-dimensional (2D) image. Early 2D echocardiographic machines generated multiple scanlines by utilizing a mechanically rotating transducer. Modern equipment, however, use electronically steered phased array transducers to generate multiple scanlines. Most ultrasound machines use between 128 and 512 phased array elements to generate pulses of ultrasound in an orderly sequence, with the result being similar to that which can be achieved with a mechanically rotating transducer, but with better spatial resolution. For standard imaging, ultrasonic transducers emit sound waves in pulses rather than continuously. An M-mode image represents a single scan line on the y-axis with time on the x-axis. The small 2D image in the upper right-hand corner shows where the M-mode "slice" is made. Although scanlines were visible in early ultrasound images, modern ultrasound equipment performs interpolation between scanlines to generate a smooth image without the appearance of scanlines. These reflections form the clearest boundaries on ultrasonic images and are termed specular reflections in which a significant proportion of the ultrasound energy is reflected back to the transducer. In contrast, reflections that occur from within relatively homogeneous tissues, such as myocardium, tend to be scattered in a variety of directions. Although some of the scattering ultrasound returns back to the transducer, the energy associated with these reflections is significantly lower than that emitted by the transducer. Finally, refraction occurs when ultrasound is reflected at an angle from the original ultrasound beam. All of these interactions with tissue are important in the ultimate image that is generated. Although ultrasound can easily traverse through bodily fluids, including water and blood, as well as most soft tissues, ultrasound does not pass easily through bone or air. This limitation represents a major problem in cardiac imaging because the heart is surrounded by the thorax (bone) and the lungs (air). Indeed, patients with emphysema, who have overexpanded lungs, can be extremely challenging to image. The limit of the resolution of ultrasound is approximately one-half of the wavelength. Although resolution can be increased by increasing the frequency of the ultrasound used, higher frequency ultrasound is less able to penetrate through tissues.
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Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects safe cholesterol levels nz buy ezetimibe us. Determination of left ventricular filling pressure by Doppler echocardiography in patients with coronary artery disease: critical role of left ventricular systolic function cholesterol levels by age ezetimibe 10 mg overnight delivery. Assessment of mitral filling patterns in response to cholesterol levels natural remedies purchase 10mg ezetimibe otc alterations in loading conditions (administration of sublingual nitroglycerin to decrease preload or passive leg raising to increase preload). Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. An 80-yr-old male with a history of hypertension who presented with acute onset of chest pain associated with mild shortness of breath and palpitations, lasting a total of 20 min by the time he was transported to the hospital. On physical exam he appeared uncomfortable, diaphoretic, tachycardic, and with a blood pressure of 90/60 mmHg. Lungs were clear to auscultation, and a cardiac exam revealed an S3 without murmurs or rub. Cardiac enzymes were sent, and the patient started on aspirin and heparin in addition to lytic therapy with Retavase. The patient was ultimately transferred to a tertiary care institution for cardiac catheterization. Apparent hypokinesis/ dyskinesis in the postero-inferior walls (B,D, arrows) was a result of external pressure from tense ascites secondary to his end-stage liver disease. Abnormal wall motion owing to insufficient blood supply to the myocardium may be graded as hypokinetic (thickening, but less than normal), akinetic (no thickening), and dyskinetic or aneurysmal (no thickening, with outward movement of the segment during systole, owing to increased intraventricular pressure on a scarred and noncontractile area of myocardial fibrosis). In general, myocardium that is transmurally infarcted tends to have more severe dysfunction, with akinetic or dyskinetic motion. It is important to carefully distinguish between wall thickening, as opposed to just epicardial or endocardial border movement during systole. Pitfalls in diagnosing wall motion abnormalities abound: these include both false-positives owing to poor visualization of the endocardium (the artifact of echo "dropout"), superior angulation of the probe such that the membranous, nonmuscular portion of the upper interventricular septum is misinterpreted as an infarct, extracardiac compression of the inferior wall by ascites or abdominal contents ("pseudodyskinesis," see. Compare these regions to the segments and coronary artery territories depicted in. In some cases, the injection of an intravenous contrast agent can help delineate endocardial borders. The main epicardial coronary arteries supply distinct territories that should be individually evaluated during the ultrasound exam. At the basal and midventricular levels, the septal and lateral walls are further subdivided into anterior and inferior sections. These main epicardial arteries give rise to intramural branches that further subdivide into subepicardial and subendocardial arterioles and capillary plexuses. In the normal heart, anastomotic branches and networks connect the major coronary arteries. These serve as the framework for collateral circulation development following total or near-total occlusion of a major epicardial artery. Anatomical left ventricular segments used in reporting regional wall motion (American Heart Association classification) and their corresponding blood supply. At least a 70% reduction in cross-sectional diameter is required before the stenosis becomes hemodynamically significant. An acute left main coronary artery occlusion can be lethal, as it supplies an extensive territory, and only the inferior septum and inferior wall would be spared. An 89-yr-old male with multiple malignancies and pre-existing coronary artery disease. This 89-yr-old male with three-vessel disease and multiple malignancies presented with chest pains and dyspnea. Diastolic images show infero-postero basal hypokinesis that were less apparent during systole. Collateral circulation develops in response to significant ischemia, and make a significant contribution to blood flow and improved ventricular function. The wall motion score index score is equal to the sum of these numbers/number of segments visualized, such that a normokinetic ventricle should have a score of 1. However, it should be kept in mind that smaller (subendocardial) coronary arteries can cause more subtle or more localized wall motion abnormalities, and thus the sensitivity of echocardiography for subendocardial ischemia is reduced. However, in the absence of visualized wall motion abnormalities, other causes of chest pain should be considered. Although noncardiac chest pain is frequently the case, other etiologies such as aortic or coronary artery dissection, pericarditis, myocarditis, and endocarditis should be considered in the differential diagnosis. Small collateral vessels from other unobstructed coronary arteries can develop and perfuse the peripheral territory of affected vessels, thus diminishing the dysfunctional territory. The segmental myocardial dysfunction can be extensive enough to cause a drop in cardiac output, leading to leftsided (and occasionally right-sided) heart failure. Many of these complications are associated with more extensive Q-wave or transmural infarcts, and their cumulative incidence appears to be decreasing in the current era of reperfusion by angioplasty or thrombolysis. Nevertheless, when they occur, they are often heralded by abrupt clinical decline (hypotension and flash pulmonary edema, i. Clinically a new harsh holosystolic murmur may be appreciated, although if the patient is extremely hypotensive and in cardiac shock, one may not be appreciated. Hence, papillary muscle rupture is seen more frequently with inferior infarcts, and more frequently involves the posterior leaflet (although there is crossover between chordae from individual papillary muscles and the corresponding leaflet). It is more common to see one head, or tip, of a papillary muscle disrupted, rather than the entire muscle trunk. By two-dimensional (2D) echocardiography, one will see a flail (or partially flail) leaflet corresponding to the ruptured supporting muscle and chordae, which prolapses into the left atrium during systole. A triangular or pyramidal mobile echodensity, which represents the head of the papillary muscle, attached to the tip of the flail leaflet is pathognomic. Flail anterior mitral valve leaflet in a 53-yr-old male with dilated cardiomyopathy. The latter risk factor is presumed to be a result of the absence of collateral flow preserving infracted segments. This 74-yr-old male presented with severe dyspnea and mitral regurgitation post-myocardial infarction. Echocardiographic images revealed avulsed papillary muscle and chordae attached to anterior mitral leaflet that prolapsed intermittently into the left atrium (apical four-chamber and apical three-chamber [A3C] views, A,C). At surgery for emergency mitral valve replacement, two-thirds of the posterolateral papillary muscle was totally detached.
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It should be noted that the human eye-and-brain is not a densitometer cholesterol cell membrane buy generic ezetimibe 10mg on-line, but a recognizer of interfaces cholesterol test affected by food purchase cheap ezetimibe. Bone density measurement by X-ray densitometry techniques is less accurate in children than adults cholesterol journal pdf discount 10mg ezetimibe visa. Recognition of osteoporosis and hyperparathyroidism by evaluations of interfaces works well in childhood. The amount of bone mass in childhood and adolescence affects quantity of bone mineral later in adulthood. In acutely and chronically demineralized bone, the trabeculae are thinner than normal, although remaining trabeculae may thicken to buttress the bone. Increased fragility may be caused by osteocytic osteolysis or by decreased bone formation. In hyperparathyroidism, less bone is also present, but cortices are more tunneled than normal, rather than thinned. Since some trabeculae are lost by the process, the remaining trabeculae thicken (possibly an attempt to maintain bony strength). Primary hyperthyroidism is due to parathyroid overactivity from adenoma or hyperplasia. The lamina dura around teeth, the equivalent of tubular bone cortex, becomes washed out and difficult to define on radiographs. The bony changes of hyperparathyroidism secondary to rickets take longer to heal than treated rickets. Metaphyseal lucent bands on radiographs during stress represent bone laid down without as much mineral content as otherwise, presumably because the body is expending energy elsewhere during a relative crisis or stress. The lucent bands are known as leukemic lines, but are also seen from intrauterine stress, from adapting to extrauterine life, or from serious illness that lasts for some time. D Clinical Presentation Almost all conditions of generalized bone demineralization are associated with increased incidence of fracture (as do the "overmineralization" conditions of osteopetrosis). Children under 10 years of age who have a slip of their capital femoral epiphysis usually have an underlying endocrine abnormality, especially hyperparathyroidism or hypothyroidism (some also have Down syndrome). Children with rickets may have swollen wrists and knees and knobby anterior rib ends (rachitic rosary) at presentation. The child who walks despite secondary hyperparathyroidism and rickets may develop bowed femurs and tibias. Pathology/Histopathology In osteoporosis, a child has less osseous tissue than normal. Imaging For generalized osteoporosis on plain images, a single lateral image of a calcaneus and nearby bones should be 622 Demineralization, Bone, Childhood selected. For rickets, a frontal image of the left knee and one of the left wrist should be obtained. For hyperparathyroidism, a hand and wrist image and, if possible, an oblique image of the mandible to observe for lamina dura around the teeth should be obtained. The hand and wrist image is a good study for all three of the above metabolic demineralization conditions. Similarly, in rickets, unmineralized cartilage extends even further into the expected metaphyseal region. Bone densitometry is valuable in clinical use especially in the evaluation of bone mineralization (see Table 1). In active hyperparathyroidism, a superscan of generalized increased activity is seen on technetium bone scan. Apparent reflex sympathetic dystrophy in children is almost always pain- or immobilization-induced disuse osteoporosis, and hence not hyperactive on bone scan, except at a fracture. Diagnosis Human beings are not densitometers, but are excellent recognizers of interfaces. As osteoporosis is established, cortices (from membranous bone) Nuclear Medicine Bone scanning is useful for detecting or confirming fractures in osteoporosis or hyperparathyroidism. Technetium-99m sestamibi scanning is used to investigate for parathyroid tumors in primary hyperparathyroidism. In oncogenic rickets or osteomalacia, nuclear imaging may Demineralization, Bone, Childhood. Osteomalacia (after Same causes as rickets in earlier physes have fused) childhood Demineralization, Bone, Childhood. The cuboid and its neighbors show a highly conspicuous difference in density between the thin surrounding zone of provisional calcification and the demineralized bone. Figure 2 (a) Florid nutritional rickets at age 6 months, with absence of the zone of provisional calcification of distal radius and ulna physes, as well as at the distal radius epiphysis, with lack of a metaphyseal collar; (b) a few days after initiation of vitamin D therapy, the zones of provisional calcification have returned, as have the collars, and unossified osteoid is beginning to fill in within the collar. Figure 3 An extraordinarily severe secondary hyperparathyroidism in an infant, with very coarse remaining trabeculae and cortex so washed out as to be barely perceivable. Metaphyseal fracture of at least the radius is one result of the metabolic change. In hyperparathyroidism, cortices have increased tunneling and appear washed out and indistinct. In hyperparathyroidism, the lamina dura around teeth vanishes by a similar process, and the calvarium may appear demineralized in a salt and pepper pattern. In both forms of osteopenia, namely, osteoporosis and hyperparathyroidism, fractures are common because of bone of decreased strength. In severe hyperparathyroidism, callus from fracture may, however, not calcify sufficiently to be seen on radiographs after 10 days, a rarity. The margins of the terminal tufts of phalanges may become discontinuous in rickets/hyperparathyroidism. Sharply defined lucent bone lesions, the so-called brown tumors, can appear in advanced hyperparathyroidism. Densitometry imaging methods usually define a value deviating from an age-matched expected value; the greater the deviation, the less bone substance is judged present. Metaphyseal and metaphyseal-equivalent (areas adjacent to acrophyseal growth plates) lucent bands are a sign of general stress for some time on the body, be it intrauterine stress, birth, leukemia and other major illness, and occasionally child abuse. A well-documented cause of lucent bands at birth is infants whose mothers received magnesium therapy late in the 624 Demography, Breast Cancer pregnancy. The most common cause of "leukemic lines" is birth, with the lucency appearing after about 10 days of age and lasting for a few months in most infants. Local demineralization is relatively well defined (termed "geographic") from slow-growing, frequently benign processes. Less-defined margins ("moth-eaten" and more severely "permeated") are signs of aggressiveness or malignancy, as popularized by Gwilym Lodwick (3). Interestingly, the sharpest margins of all are from the most sudden situation, acute fracture. Although Langerhans cell histiocytosis skull lesions tend to have geographic margins, long bone lesions in this condition often have poorly defined margins, although associated periosteal reaction can be quite solid. In general, thick, solid periosteal reaction reflects slower processes than thin, multilayered, or perpendicular hair-on-end periosteal reaction. Carcinoma, Breast, Demography Benign tumor which may become very aggressive with extensive local invasion.
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Additional diversity cholesterol and sugar purchase ezetimibe online pills, termed combinatorial diversity cholesterol lowering foods beans purchase 10mg ezetimibe otc, results from the random recombination of separate V cholesterol levels total order ezetimibe 10mg on line, D, and J gene segments to form a complete V-region exon. Variability at the joints between segments is increased by the insertion of random numbers of P- and N-nucleotides and by variable deletion of nucleotides at the ends of some coding sequences. The association of different light- and heavy-chain V regions to form the antigen-binding site of an immunoglobulin molecule contributes further diversity. Finally, after an immunoglobulin has been expressed, the coding sequences for its V regions are modified by somatic hypermutation upon stimulation of the B cell by antigen. The combination of all these sources of diversity generates a vast repertoire of antibody specificities from a relatively limited number of genes. The mechanism by which B-cell antigen receptors are generated is such a powerful means of creating diversity that it is not surprising that the antigen receptors of T cells bear structural resemblances to immunoglobulins and are generated by the same mechanism. In this part of the chapter we describe the organization of the T-cell receptor loci and the generation of the genes for the individual T-cell receptor chains. The T-cell receptor loci comprise sets of gene segments and are rearranged by the same enzymes as the immunoglobulin loci. Like immunoglobulin heavy and light chains, T-cell receptor and chains each consist of a variable (V) aminoterminal region and a constant (C) region (see Section 3-10). The organization of the gene segments is broadly homologous to that of the immunoglobulin gene segments (see Sections 4-2 and 4-3). A cluster of 61 J gene segments is located a considerable distance from the V gene segments. The T-cell receptor gene segments rearrange during T-cell development to form complete V-domain exons. T-cell receptor gene rearrangement takes place in the thymus; the order and regulation of the rearrangements will be dealt with in detail in Chapter 7. Essentially, however, the mechanics of gene rearrangement are similar for B and T cells. All known defects in genes that control V(D)J recombination affect T cells and B cells equally, and animals with these genetic defects lack functional lymphocytes altogether (see Section 4-5). Functional - and -chain genes are generated in the same way that complete immunoglobulin genes are created. For the chain (upper part of figure), a V gene segment rearranges to a J gene segment to create a functional V-region exon. For the chain (lower part of figure), like the immunoglobulin heavy chain, the variable domain is encoded in three gene segments, V, D, and J. The and chains pair soon after their biosynthesis to yield the: T-cell receptor heterodimer. Not all J gene segments are shown, and the leader sequences preceding each V gene segment are omitted for simplicity. The numbers of human T-cell receptor gene segments and the sources of T-cell receptor diversity compared with those of immunoglobulins. Somatic hypermutation as a source of diversity in immunoglobulins is not included in this figure. The main differences between the immunoglobulin genes and those encoding T-cell receptors reflect the fact that all the effector functions of B cells depend upon secreted antibodies whose different heavy-chain C-region isotypes trigger distinct effector mechanisms. The effector functions of T cells, in contrast, depend upon cell-cell contact and are not mediated directly by the T-cell receptor, which serves only for antigen recognition. There is only one C gene and, although there are two C genes, they are very closely homologous and there is no known functional distinction between their products. The extent and pattern of variability in T-cell receptors and immunoglobulins reflect the distinct nature of their ligands. The antigen-recognition sites of T-cell receptors would therefore be predicted to have a less variable shape, with most of the variability focused on the bound antigenic peptide occupying the center of the surface in contact with the receptor. In spite of differences in the sites of variability, the three-dimensional structure of the antigen-recognition site of a Tcell receptor looks much like that of an antibody molecule (see Sections 3-11 and 3-7, respectively). T-cell receptor loci have roughly the same number of V gene segments as do the immunoglobulin loci, but only B cells diversify rearranged V-region genes by somatic hypermutation. Thus, the center of the T-cell receptor will be highly variable, whereas the periphery will be subject to relatively little variation. A minority of T cells bear T-cell receptors composed of and chains (see Section 3-19). Increased junctional variability in the chains may compensate for the small number of V gene segments and has the effect of focusing almost all of the variability in the: receptor in the junctional region. As we have seen, the amino acids encoded by the junctional regions lie at the center of the T-cell receptor binding site. Uniquely, the locus encoding the chain is located entirely within the -chain locus. T cells bearing: receptors are a distinct lineage of T cells whose functions are at present unknown. Detailed analysis of the rearranged V regions of: T-cell receptors shows that they resemble the V regions of antibody molecules more than they resemble the V regions of: T-cell receptors. When we discussed the generation of antibody diversity in Section 4-9, we saw that somatic hypermutation increases the diversity of all three complementarity-determining regions of both immunoglobulin chains. Why T-cell and B-cell receptors differ in their abilities to undergo somatic hypermutation is not clear, but several explanations can be suggested on the basis of the functional differences between T and B cells. Because the central role of T cells is to stimulate both humoral and cellular immune responses, it is crucially important that T cells do not react with self proteins. T cells that recognize self antigens are rigorously purged during development (see Chapter 7) and the absence of somatic hypermutation helps to ensure that somatic mutants recognizing self proteins do not arise later in the course of immune responses. This constraint does not apply with the same force to B-cell receptors, as B cells usually require T-cell help to secrete antibodies. A B cell whose receptor mutates to become self reactive would, under normal circumstances, fail to make antibody for lack of self-reactive T cells to provide this help (see Chapter 9). However, the strongest argument for this difference between immunoglobulins and T-cell receptors is the simple one that somatic hypermutation is an adaptive specialization for B cells alone, because they must make very high-affinity antibodies to capture toxin molecules in the extracellular fluids. We will see in Chapter 10 that they do this through somatic hypermutation followed by selection for antigen binding. T-cell receptors are structurally similar to immunoglobulins and are encoded by homologous genes. T-cell receptor genes are assembled by somatic recombination from sets of gene segments in the same way as are the immunoglobulin genes. Diversity is distributed differently in immunoglobulins and T-cell receptors; the T-cell receptor loci have roughly the same number of V gene segments but more J gene segments, and there is greater diversification of the junctions between gene segments during gene rearrangement. Moreover, functional T-cell receptors are not known to diversify their V genes after rearrangement through somatic hypermutation. This leads to a T-cell receptor in which the highest diversity is in the central part of the receptor, which contacts the bound peptide fragment of the ligand. So far we have focused on the structural variation inherent in the assembly of the V regions of the antibody molecule and T-cell receptor. We have seen how this variation creates a diverse repertoire of antigen-specificities, and we have also considered how these variable regions are attached to constant regions in the monovalent heterodimeric T-cell receptor, and the Y-shaped four-chain structure of the divalent immunoglobulin molecule.
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Although all immunoglobulin molecules are constructed from a basic unit of two heavy and two light chains cholesterol levels below 100 10mg ezetimibe mastercard, both IgM and IgA can form multimers cholesterol cell membrane definition cheapest ezetimibe. An additional separate 15 kDa polypeptide chain called the J chain promotes polymerization by linking to cholesterol levels good range order generic ezetimibe on-line the cysteines of the tailpiece, which is found only in the secreted forms of the and chains. IgM molecules are found as pentamers, and occasionally hexamers (without J chain), in plasma, whereas IgA in mucous secretions, but not in plasma, is mainly found as a dimer (see. In pentameric IgM, the monomers are cross-linked by disulfide bonds to each other and to the J chain. IgM can also form hexamers that lack a J chain but are more efficient in complement activation. The polymerization of immunoglobulin molecules is thought to be important in the binding of antibody to repetitive epitopes. The dissociation rate of an individual epitope from an individual antibody binding site influences the strength of binding, or affinity, of that site: the lower the dissociation rate, the higher the affinity (see Appendix I, Section A-9). An antibody molecule has two or more identical antigen-binding sites, and if it attaches to two or more repeating epitopes on a single target antigen, it will only dissociate when all sites dissociate. The dissociation rate of the whole antibody from the whole antigen will therefore be much slower than the rate for the individual binding sites, giving a greater effective total binding strength, or avidity. This consideration is particularly relevant for pentameric IgM, which has ten antigen-binding sites. IgM antibodies frequently recognize repetitive epitopes such as those expressed by bacterial cell-wall polysaccharides, but the binding of individual sites is often of low affinity because IgM is made early in immune responses, before somatic hypermutation and affinity maturation. Multisite binding makes up for this, dramatically improving the overall functional binding strength. When an immunoglobulin is used as an antigen, it will be treated like any other foreign protein and will elicit an antibody response. Anti-immunoglobulin antibodies can be made that recognize the amino acids that characterize the isotype of the injected antibody. Such anti-isotypic antibodies recognize all immunoglobulins of the same isotype in all members of the species from which the injected antibody came. It is also possible to raise antibodies that recognize differences in immuno-globulins from members of the same species that are due to the presence of multiple alleles of the individual C genes in the population (genetic polymorphism). In contrast to anti-isotypic antibodies, anti-allotypic antibodies will recognize immuno-globulin of a particular isotype only in some members of a species. Finally, as individual antibodies differ in their V regions, one can raise antibodies against unique sequence variants, which are called idiotypes. A schematic picture of the differences between idiotypes, allotypes, and isotypes is given in. Historically, the main features of immunoglobulins were defined by using isotypic and allotypic genetic markers identified by antisera raised in different species or in genetically distinct members of the same species (see Appendix I, Section A10). The independent segregation of allotypic and isotypic markers revealed the existence of separate heavy-chain, and genes. The isotypes of immunoglobulins are defined by their heavy-chain C regions, each isotype being encoded by a separate C-region gene. Unlike V(D)J recombination, isotype switching is always productive and occurs only in B cells activated by antigen. The immunological functions of the various isotypes differ; thus, isotype switching varies the response to the same antigen at different times or under different conditions. In this way, the B-cell antigen receptor has the same specificity as the antibody that the B cell secretes upon activation. Lymphocyte receptors are remarkably diverse, and developing B cells and T cells use the same basic mechanism to achieve this diversity. In each cell, functional genes for the immunoglobulin and T-cell receptor chains are assembled by somatic recombination from sets of separate gene segments that together encode the V region. The substrates for the joining process, arrays of V, D, and J gene segments, are similar among all the receptor loci, though there are some important differences in the details of their arrangement. As each type of gene segment is present in multiple, slightly different, versions, the random selection of gene segments for assembly is the source of enormous potential diversity. During the process of assembly, further diversity is introduced at the gene segment junctions through imprecise joining mechanisms. The independent association of the two chains of immunoglobulins or T-cell receptors multiplies the overall diversity of the complete antigen receptor. An important difference between immunoglobulins and T-cell receptors is that immunoglobulins exist in both membrane-bound (B-cell receptors) and secreted forms (antibodies). Heavy-chain C regions contain three or four immunoglobulin domains, whereas the T-cell receptor chains have only one. Antibodies also have a variety of effector functions that are mediated by their C regions. Moreover, there are several alternative heavy-chain C regions for immunoglobulins, each with different effector functions. The same V region can be expressed along with different C regions through a process known as isotype switching. In this way, the progeny of a single B cell can express multiple different isotypes, thus maximizing the possible effector functions of any given antigen-specific antibody. The changes in immunoglobulin and T-cell receptor genes that occur during B-cell and T-cell development are summarized in. Changes in immunoglobulin and T-cell receptor genes that occur during B-cell and T-cell development and differentiation. The B-cell-specific processes, such as switch recombination, allow the same variable (V) region to be attached to several functionally distinct heavy-chain C regions, and thereby create functional diversity in an irreversible manner. By contrast, the expression of IgM versus IgD, and of membrane-bound versus secreted forms of all immunoglobulin types, can in principle be reversibly regulated. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions Proc. The arrangement of immunoglobulin and T-cell receptor genes in human lymphoproliferative disorders Adv. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain Proc. Mouse variable-region gene families complexity, polymorphism, and use in nonautoimmune responses Immunol. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene Proc. Sequences at the somatic recombination sites of immunoglobulin light-chain genes Nature 1979. Lack of N regions in antigen receptor variable region genes of TdTdeficient lymphocytes [published erratum appears in Science 1993, 262:1957] Science 1993. Rearrangement of genetic information may produce immunoglobulin diversity Nature 1978. Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots Proc. Monitoring and interpreting the intrinsic features of somatic hypermutation Immunol. TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line Immunity 1998.
- Smog or chemicals in the air or wind
- Breathing problems
- If so, what type (blurring, reduced vision, or other) and how much?
- Making excuses to use drugs
- Bluish skin due to lack of oxygen (cyanosis) - emergency treatment is needed
- Over-the-counter antihistamines (such as Dramamine)
- Avoid taking medicines that cause blood vessels to tighten or spasm.
- Have severe chest pain or tightness
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It must be stressed that all drugs have to cholesterol levels chart in uk purchase ezetimibe with amex be carefully titrated according to nutrition cholesterol lowering foods buy on line ezetimibe response cholesterol control chart buy cheap ezetimibe 10mg line. Many patients in low-resource countries have had limited exposure to opioids and can be very sensitive to them. Poor renal and liver function could lead to reduced metabolism and excretion, increasing the cumulative effects of drugs. Careful titration, use of multiple analgesics, and good monitoring hold the key to safe and successful management. This patient must be pain-free to mobilize quickly and have physiotherapy in the perioperative period. Complications from drug interactions and complications from multiple drug usage should be avoided. What is the incidence and severity of postoperative pain in joint replacement patients? Joint replacements constitute some of the most destructive types of surgery and are usually very painful. Most of these patients have been in a lot of pain even before surgery and are already on many drugs and other forms of treatment. Their pain will be moderate (Grade 3) or severe (Grade 4), and bad enough to limit movement and normal activity. We can therefore assume that most will have unbearable pain after their surgery, especially when physiotherapists start mobilizing them within one or two days after the operation. Very poor-risk patients like this one ideally will require respiratory and cardiovascular support in a high-dependency or intensive care unit. Since most hospitals in low-resource countries do not have these facilities, great caution must be exercised when using any drugs for pain relief, and careful monitoring of the cardiovascular, respiratory, and urine output should be routine. Central nervous system manifestations such as agitation or coma may make it difficult to interpret the sedation score. The delayed recovery of consciousness could also be due to the cumulative effects of sedatives and longacting opioids used for sedation and ventilation. The take-home message would be: the general poor state of the patient and the fear of hypotension should not be reasons to avoid the use of opioids in this What other problems do we have to consider regarding pain management? Some may be on steroids and other drugs for rheumatoid arthritis and other medical conditions. These drugs may have been taken for long periods, and side effects or drug interactions are not uncommon in the perioperative period. The elderly have considerable multisystem pathology, and they may be on cardiovascular, respiratory, central nervous system, and genitourinary drugs. They may be on blood-thinning drugs such as warfarin, aspirin, and any of the heparins, which may affect our regional and local anesthetic blocks. Pain Management after Major Surgery the socioeconomic status of these patients is very important. If they have dementia and cannot communicate very well, pain management can be very difficult. Intravenous acetaminophen is now more affordable and convenient than rectal acetaminophen and should be used more often, even in low-resource countries. For pain relief during and immediately after the operation, regional anesthesia is probably best for this group of patients. The duration of the operation, patient cooperation, and technical difficulties, as well as anticoagulant therapy, may make general anesthesia mandatory. Spinal anesthesia with long-acting local anesthetic drugs together with intrathecal opioids will provide a simple and effective anesthesia and good postoperative analgesia. This method is well suited for any lowresource country because patients receiving this type of anesthesia require less resources and care than patients who have general anesthesia. Small doses of diamorphine given intrathecally with the local anesthetic drugs can provide good analgesia for up to 24 hours postoperatively. The clinician should, however, only use preservativefree morphine in the intrathecal or epidural space and should be aware of the problems associated with morphine use, which include delayed respiratory depression, itching, nausea, vomiting, and urinary retention. Patients on aspirin and some prophylactic anticoagulation can have spinal anesthesia, provided that hematological profiles are kept within normal ranges and that care is taken with timing and concurrent use of prophylactic heparins. Clopidogrel and some newer drugs used in richer countries cause more problems and have to be stopped at least 7 days before surgery and regional anesthesia. This treatment is more expensive, and the incidences of complications with anticoagulants are higher. Perioperative pain management plans should be meticulously put in place well in advance of operations like this one. The surgeon, anesthetist, and acute pain team (if available) should involve the patient and the relatives before the operation to discuss the options. Special forms, written instructions, and guidelines make things easier for patients and hospital staff. In uncooperative or demented patients with no family support, the safest and most appropriate techniques should be used, and extra care should be taken in monitoring them. These are just two examples of major surgery that one can come across in poorly resourced countries. There are many other operations, types of patients, and issues that one will come across in managing pain after major surgery in these countries. It only became possible to perform major operations safely and painlessly after modern anesthesia was introduced about a century ago. In the perioperative period, certain pathophysiological 106 changes caused by pain threaten the wellbeing and the rehabilitation of the patient. Pain is part of the "stress response complex" to prepare the patient for "fight or flight. One must therefore understand the pain process and make good use of available resources judiciously, wherever one is practicing. Frank Boni need treatment, these figures suggest that only about half of patients will need postoperative analgesia after major surgery. A closer look at publications, which are mostly from developed countries, reveals that these figures are for patients who have had analgesia during and after operations and yet still had pain. A good proportion of patients in developing countries will not complain of pain-although they may be in agony-because of cultural and other reasons. In the absence of reliable data in poorly resourced countries, we can only assume that most patients will have moderate to severe pain after major surgery. The real incidence of untreated postoperative pain may never be known because it would be unethical to carry out properly controlled studies by deliberately allowing some patients to have pain after major surgery.
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Diagnosis the diagnosis of nasopharyngeal neoplasms is based on histopathology obtained by biopsy during rhinoscopy cholesterol medication starts with l purchase ezetimibe 10 mg. Nuclear Medicine Nuclear medicine techniques are not routinely employed in nasopharyngeal neoplasms cholesterol chart mmol generic 10 mg ezetimibe free shipping, but they can provide relevant information in certain cases cholesterol test results non fasting purchase 10 mg ezetimibe otc. Nevertheless, the major role of this nuclear medicine technique is its high value in detecting residual or recurrent neoplastic tissue following radiotherapy. Although tumors of the nose and paranasal sinuses are uncommon, accounting for only 0. The tumor behaves like a benign infectious disease in the beginning, with the actual diagnosis only being made in the advanced stage thereby explaining the overall poor prognosis of malignancies in this region. An increased risk is observed in those exposed to nickel, chromium pigment, bantu snuff, thorotrast, mustard gas, polycyclic hydrocarbons, and cigarette smoke, as well as in wooden furniture, isopropyl alcohol, and radium production workers (2, 3). Adenoid cystic carcinoma is the most common minor salivary gland tumor, accounting for one-third of these malignancies, and more than 80% originate from the maxillary sinus and nasal cavity (3). Perineural invasion with secondary invasion of the orbit and intracranial compartments is common. Approximately one-half of the patients have distant metastasis to the lungs, brain, and bones (3). Adenocarcinomas are more commonly found in the upper nasal cavity and ethmoid sinuses. The prognosis depends on the differentiation of the tumor and is comparable with that of adenoid cystic carcinoma (2, 3). It is believed that nasal melanomas originate from melanocytes that migrated from the neural crest to the mucosa of the sinonasal cavity during embryological development. The cervical nodal metastasis rate is 40% and local recurrence is seen in two-thirds of patients. Nasal melanomas have a better prognosis than those originating in the paranasal sinuses (3). Olfactory neuroblastomas (esthesioneuroblastomas) are rare neoplasms of the cribriform region and arise from the olfactory nerves. Subarachnoid seeding occurs because of direct extension of the tumor or after surgery (3). A variety of benign neoplasms such as osteoma, chondroma, schwannoma, neurofibroma, ossifying fibroma, cementoma, and odontogenic tumors can arise from the sinonasal cavity. Some are classified as intermediate neoplasms, such as inverted papilloma, meningioma, hemangioma, and hemangiopericytoma. Juvenile fibroangioma can be considered as a rare, benign, highly vascularized tumor of the nasosinusal region because of its particular growth. Recurrence is likely due to the locally aggressive behavior of hemangiopericytoma (3). N Clinical Presentation the clinical presentation of sinonasal tumors depends on the site of origin, size, vascularization, and pathway of tumor diffusion. The main symptoms can be summarized as follows: nasal obstruction, epistaxis and nasal discharge, exophthalmos due to orbital involvement, and cranial nerve impairment due to involvement of the skull base with secondary perineural extension. To distinguish the clinical and radiological appearance of neoplasms in the paranasal sinuses and nasal cavity from coexistent inflammatory changes that usually occur with such tumors, it is necessary to be familiar with the normal anatomy or anatomical variations and the drainage pattern of sinus secretions. Basically, the paranasal sinuses are composed of four pairs of sinuses: frontal, maxillary, ethmoidal, and sphenoid sinuses. The most prognostically significant structures are above and behind the maxillary antrum. The sphenoid sinus is in the center of the head and is related to very complex structures: the optic nerve and pituitary gland are superior to it and the internal carotid artery and cavernous sinuses sit laterally. Thus, the complete resection of a malignancy involving the sphenoid is occasionally possible (2). Detailed knowledge about the anatomical boundaries of the paranasal sinuses is essential to map the extent of the disease and to plan the surgical resection and reconstruction preoperatively (2). Note the extensive destruction of the bones and invasion into the paranasal soft tissues. Figure 2 Olfactory neuroblastoma, a rare neoplasm arising from the olfactory epithelium and found in the upper nasal cavity. The role of the radiologist is to provide accurate information about the tumor location and mapping, and to detect critical areas of involvement, which may alter surgical approach and treatment planning. The hallmark of malignancies involving the sinonasal cavity is the presence of osseous destruction (4). Skull base invasion is more commonly seen in malignant lesions such as carcinomas, lymphomas, and sarcomas. The pattern of osseous destruction of benign and malignant lesions is similar at the skull base, because osseous remodeling in this location is unusual (3). Osseous destruction with the involvement of orbital fat suggests orbital invasion. Presence of nodularity at the interface between the tumor and periorbita, assessment of the extraocular muscles (enlargement, displacement, and signal abnormalities), and evaluation of the integrity of the osseous structures including the orbital walls adjacent to the tumor are further criteria for orbital invasion. Carcinomas of the nasal cavity and paranasal sinuses share similar gross and microscopic pathological characteristics. In postoperative patients, differentiating the residue and the recurrent tumor from the granulation tissue is also a problem. In conclusion, paranasal sinus neoplasms are difficult to diagnose in early stages of the disease. A high index of clinical suspicion leading to more detailed studies is therefore necessary. Use of different imaging technologies is essential and crucial for planning a treatment strategy. Interventional Radiological Treatment Embolization of juvenile angiofibroma is the only application of radiological interventional procedures. They are in the majority of cases benign although some malignant odontogenic tumors have been reported. Odontogenic carcinoma is a carcinoma arising within the jawbone without a lesion of the mucosa (1). It can be subcategorized in: malignant ameloblastoma, when it represents a malignant transformation of a benign ameloblastoma; primary intraosseous carcinoma; carcinoma arising in preexisting odontogenic cyst. Goldenberg D, Golz A, Fradis M et al (2001) Malignant tumors of the nose and paranasal sinuses: a retrospective reveiw of 291 cases. Odontogenic cysts are epithelial-lined structures derived from odontogenic epithelium containing fluid or semisolid material (2). Odontogenic tumors may the most common odontogenic cyst is periapical (radicular) cyst, an inflammatory cyst that results from a periapical granuloma. It arises by Malassez epithelial rests stimulation by chronic apical periodontitis due to periapical diffusion of a pulp infection in carious teeth. The cyst wall, lined by stratified nonkeratinizing squamous epithelium, may show inflammatory changes. Dentigerous (follicular) cyst, the second most common odontogenic cyst, forms within the normal dental follicle.
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Do not clean probes with chlorhexidine type of cholesterol in shrimp order ezetimibe 10mg mastercard, isopropyl alcohol cholesterol under eyes ezetimibe 10 mg cheap, or alcohol-containing cleaners as they will damage the probe cholesterol test how much blood purchase 10 mg ezetimibe with mastercard. Ensure adequate contact by using enough ultrasound gel and applying comfortable pressure on the skin. Depth: Adjust to visualize structure of interest and at least a centimeter of tissue below that structure. Indications: Blood sampling in infants for laboratory studies less affected by hemolysis. Puncture heel using a lancet on the lateral part of the heel, avoiding the posterior area. Puncture finger using a lancet on the palmar lateral surface of the finger near the tip. Wipe away the first drop of blood, and then collect the sample using a capillary tube or container. Alternate between squeezing blood from the leg toward the heel (or from the hand toward the finger) and then releasing the pressure for several seconds. Indications: Blood sampling and access to peripheral venous circulation to deliver fluid, medications, or blood products. After removing tourniquet, attach a syringe and apply gentle negative pressure to withdraw blood for serum sampling. With ultrasound, identify a vein that does not appear to branch or to be tortuous. Perform this by sliding the probe along the course of the vessel and identifying its direction and branching. The saphenous veins in the calves, veins in the forearms, antecubital areas, inside of the upper arms, and external jugular veins are areas where ultrasound guidance can help. Prepare the site, and in the case of limb vessels, place a tourniquet proximal to the insertion site. Infiltration around deeper vessels is also a risk, as a shorter length of catheter resides in the vessel after insertion. Insert the needle into the skin at a shallow (usually <30-degree) angle to the skin at the midline of the probe near where it contacts the skin. With the probe visualizing the vessel transversely, slowly advance the needle and follow the tip of the needle by sliding the probe away from you. Proceed with cannulation of the vessel and secure the intravenous catheter per standard procedure. Indications: Blood sampling in patients with inadequate peripheral vascular access or during resuscitation. Restrain patient securely and place with head turned away from side of cannulation. Position with towel roll under shoulders or with head over side of bed to extend neck and accentuate the posterior margin of the sternocleidomastoid muscle on the side of venipuncture. The external jugular vein will distend if its most proximal segment is occluded or if the child cries. The vein runs from the angle of the mandible to the posterior border of the lower third of the sternocleidomastoid muscle. With continuous negative suction on the syringe, insert the needle at about a 30-degree angle to the skin. Enter the vein at the point where it crosses the 3 34 Part I Pediatric Acute Care sternocleidomastoid muscle. Indications: Arterial blood sampling or frequent blood gas and continuous blood pressure monitoring in an intensive care setting. Complications: Infection, bleeding, occlusion of artery by hematoma or thrombosis, ischemia if ulnar circulation is inadequate. Before the procedure, test adequacy of ulnar blood flow with the Allen test: Clench the hand while simultaneously compressing ulnar and radial arteries. It is optional to infiltrate the area over the point of maximal impulse with lidocaine. Puncture: Insert a butterfly needle attached to a syringe at a 30-to 60-degree angle over the point of maximal impulse. Once the sample is obtained, apply firm, constant pressure for 5 minutes and then place a pressure dressing on the puncture site. Prepare the wrist with sterile technique and infiltrate over the point of maximal impulse with 1% lidocaine. Alternatively, pass the needle and catheter through the artery to transfix it, and then withdraw the needle. Very slowly, withdraw the catheter until free flow of blood is noted, then advance the catheter and secure in place using sutures or tape. Apply a sterile dressing and infuse heparinized isotonic fluid (per protocol) at a minimum of 1 mL/hr. Suggested size of arterial catheters based on weight: (1) Infant (<10 kg): 24 G or 2. After the sterile field has been prepped, apply gel to the probe and place within a sterile cover. Place the ultrasound probe transverse to the artery on the radial, posterior tibial, or dorsalis pedis pulse. In the left image, the radial artery is seen in cross section with veins on either side. On the right image, pressure has been applied and the veins are collapsed while the artery remains patent. Insert the needle into the skin at a 45-degree angle at the midline of the probe near where it contacts the skin. With the probe visualizing the vessel transversely, slowly advance the needle and follow the tip of the needle by sliding the probe away. Indications: Arterial blood sampling when radial artery puncture is unsuccessful or inaccessible. Posterior tibial artery: Puncture the artery posterior to medial malleolus while holding the foot in dorsiflexion. Dorsalis pedis artery: Puncture the artery at dorsal midfoot between first and second toes while holding the foot in plantar flexion. Complications: Infection, bleeding, arterial or venous perforation, pneumothorax, hemothorax, thrombosis, catheter fragment in circulation, air embolism. Ultrasound guidance: Has become standard practice to facilitate placement of internal jugular vein central venous catheters. It has been shown to reduce insertion time as well as complication rates when effectively implemented in certain anatomic areas. Subclavian vein: Risks include pleural injury, pneumothorax, hemothorax, or pleural infusion causing hydrothorax as well as subclavian artery injury. The artery below the clavicle is not compressible and therefore inadvertent puncture is life threatening in patients with a coagulopathy.