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By L. Kan. University of North Dakota--Lake Region.

For motor behaviors that are performed in two dimensions — for example generic extra super levitra 100 mg with amex, the reaching movements in monkeys — one might conceptualize such a field as a plane with a relatively shallow slope extra super levitra 100 mg visa. Of course 100mg extra super levitra mastercard, we currently lack the type of complete quantitative data that would be necessary in order to construct such putative gain fields accurately buy extra super levitra 100 mg online, but systematic studies of this issue are currently being conducted. We predict that the slope of such gain fields is likely to be small and that the representation of space by the motor cortex, as in the parietal cortex,56 is likely to be distributed. Bizzi and colleagues57–60 have shown, in experiments in the frog and rat, that a set of “motor primitives,” which could form the basis of activating specific sets of muscles during multiple joint movement, can be elicited through microsimulation of the spinal gray matter. These primitives may form the building blocks for voluntary movement by translating spatial signals from the motor cortex into appropriate muscle output. Recent data from experiments using long trains of intracortical microstimulation suggest that the motor cortex may be able to access such primitives directly. These propriospinal interneurons may participate in the integration of reaching movements at a spinal level, and may effectively translate signals from cells in the motor cortex that relate to the direction of force output of the whole limb55 into appropriate patterns of muscle activation. It is likely that the association between motor cortex cell activity and motor primitive “modules” at another level in the motor system is established through learning and adaptation. Though conceptually attractive, the idea of successive coordinate transforma- tions in frontal motor areas culminating in a muscle or joint based coding of motor output in motor cortex63 does not have strong experimental support and should be abandoned, at least as applied to skilled movements. The search for a direct reflection of the motor periphery in the motor cortex is likely to be as futile as the quest for the representation of the single muscle. The well- defined goal, moving the hand to a spatial location, makes it a popular paradigm for exploring sensorimotor function. This conversion of sensory to motor signals involves many cortical and subcortical regions of the CNS, and a major focus of research is to identify the role played by each of these regions. While cells are unlikely literally to code any engineering- inspired variable, it is nonetheless valuable (and even necessary) to relate neural activity to some features of behavior reflecting sensory, cognitive, or motor aspects of the task. How one chooses which variable to correlate depends highly on the conceptual framework used to develop the experiment. This chapter starts with the important issue of how theoretical concepts guide experimental design and data analysis. I will describe two conceptual frameworks for interpreting neural activity during reaching: sensorimotor transformations and inter- nal models. Both frameworks address the same biological problem: How does the brain control the limb to reach toward a spatial target? The key difference is that each framework focuses attention on a different aspect of the motor task and thus each leads to different experiments. The sensorimotor transformations framework has been used extensively over the past 20 years to guide neurophysiological exper- iments on reaching, whereas the internal models framework has only recently had an impact on experimental design. The second half of this chapter illustrates how the notion of internal models can be used to explore the neural basis of movement. A new experimental facility is described that can sense and perturb multiple-joint planar movements and this is followed by a brief description of the mechanics of limb movement. Finally some preliminary observations are presented on neural correlates in the primary motor cortex (M1) of the mechanical properties of the limb and of external mechanical loads. The use of intermediary repre- sentations to plan and control movement seems like a reasonable assumption, par- ticularly given the ubiquitous observation that hand trajectories are relatively straight for point-to-point reaching movements. As described below, some experiments Copyright © 2005 CRC Press LLC A Target Hand Joint Joint Muscle Location Kinematics Kinematics Torques Activity B Muscle + Activity Desired State Internal Model + Musculoskeletal Limb Movement (Limb Position) of Musculoskeletal System - System - Central Sensory Feedback: Nervous System (Vision, Proprioception) FIGURE 6. This framework leads to the scientific problem of identifying how these representations are reflected in the discharge pattern of neurons in different brain regions. This framework leads to the scientific problem of identifying how information related to the motor periphery and physical loads is reflected in the discharge pattern of neurons. In other cases, a specific class of variable has been chosen a priori, either based on the results of previous studies or simply for technical reasons.

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Certain areas of the epithelium that form the outer layer of the skin are capable of modifying them- selves for greater strength whenever they are subjected to unusual wear and tear; the growth of calluses is a good example of this response buy extra super levitra 100 mg visa. This is so ex- tensive and widely distributed that if Lining of we were able to dissolve all the tissues trachea Pseudostratified except connective tissue order extra super levitra 100 mg otc, we would columnar epithelium still be able to recognize the contours A of the entire body buy extra super levitra 100mg online. Examples of exocrine glands include the glands in cells in liquid connective tissue are suspended in a fluid the gastrointestinal tract that secrete digestive juices 100 mg extra super levitra, the environment. These secretions, called hor- Checkpoint 4-3 Connective tissue varies according to the com- mones, have effects on specific tissues known as the position of the material that is between the cells. This type of elastic B Branched tubular connective tissue appears in the vocal cords, the passage- ways of the respiratory tract, and the walls of the large ar- teries (blood vessels). If the fibers in the connective tis- sue are all arranged in the same direction, like the strands C Coiled tubular of a cable, the tissue can pull in one direction. A common form of cartilage known as hyaline (HI-ah-lin) cartilage forms the tough, translucent material, popularly called gristle, seen over the ends of the long bones (see Fig. E Compound Another form of cartilage, fibrocartilage (fi-bro-KAR- tih-laj), is found between segments of the spine, at the an- Figure 4-4 Some structural types of exocrine glands. The cells that produce cartilage are chondrocytes (KON-dro-sites), a name derived from the word root chon- dro, meaning “cartilage” and the root cyto, meaning “cell. Cells Collagen ◗ Muscle Tissue Muscle tissue is designed to produce Elastic movement by contraction of its cells, fibers which are called muscle fibers because most of them are long and threadlike. The cells in skeletal muscle are very large and are remarkable in having Stored fat multiple nuclei and a pattern of dark and light banding described as C striations. This tissue gradually becomes has branching cells and specialized membranes be- impregnated with salts of calcium and phosphorus that tween the cells that appear as dark lines under the mi- make bone characteristically solid and hard. In the skin and membranes Greek word meaning “glue,” reveals its role as the main struc- covering muscles and organs, collagen fibers are arranged ir- tural protein in connective tissue. The result is a Fibroblasts secrete collagen molecules into the surrounding tissue that can resist stretching forces in many different direc- matrix, where the molecules are then assembled into fibers. Striations Nerves from even the most remote parts of the body come together and form a great trunk cable called the spinal cord, which in turn leads into Nuclei the central switchboard of the brain. Be- cause the outer layer of the brain has ◗ Nervous Tissue large collections of cell bodies and unmyelinated fibers, the brain is popularly termed gray matter, even though its The human body is made up of countless structures, both interior is composed of white matter (see Fig. For all the workers in the corporation to coordinate their ef- Nervous tissue is supported by specialized cells known as forts, there must be some central control, such as the neuroglia (nu-ROG-le-ah) or glial (GLI-al) cells, which president or CEO. Each structure of the body is in direct communica- Some of these cells protect the brain from harmful sub- TISSUES, GLANDS, AND MEMBRANES ✦ 65 4 and the movement of joints. Epithelial Gray matter membranes are of several types: ◗ Serous (SE-rus), membranes line the White matter walls of body cavities and are folded back onto the surface of internal or- gans, forming their outermost layer. The thin epithelium of serous mem- A more detailed discussion of nervous tissue and the branes is a smooth, glistening kind of tissue called nervous system can be found in Chapters 9 and 10. Their properties vary: covers the organs of the abdomen, and forms supporting some are fragile, others tough; some are transparent, oth- and protective structures within the abdomen (see Fig. They may contain cells that secrete lubricants to forms the lining of a closed cavity, while another part ease the movement of organs, such as the heart and lung, folds back to cover the surface of the organ contained in 66 ✦ CHAPTER FOUR that cavity. The relationship between an organ and the fibrous sac (the fibrous pericardium) that encloses the serous membrane around it can be visualized by imagin- heart (see Fig. Because internal organs are called viscera, the portion Your fist is the organ and the serous membrane around it of the serous membrane attached to an organ is the vis- is in two layers, one against your fist and one folded back ceral layer. Portions of the peritoneum that cover organs in the ab- The portion of the serous membrane attached to the domen are named according to the particular organ in- wall of a cavity or sac is known as the parietal (pah-RI- volved. Parietal pleura lines the normally are in direct contact with a minimal amount of thoracic (chest) cavity, and parietal pericardium lines the lubricant between them. The cells that line the nasal cavities and the passageways of the respiratory tract are supplied with tiny, hairlike extensions called cilia, described in Chapter 3.

Pterygium colli—Webbing or broadening of the Cryptorchidism—A condition in which one or both neck purchase extra super levitra 100 mg online, usually found at birth generic extra super levitra 100mg free shipping, and usually on both testes fail to descend normally cheap extra super levitra 100 mg otc. Cystic hygroma—An accumulation of fluid behind Pulmonary stenosis—Narrowing of the pulmonary the fetal neck generic extra super levitra 100mg visa, often caused by improper drainage of valve of the heart, between the right ventricle and the lymphatic system in utero. Neurofibromatosis—Progressive genetic condition often including multiple café-au-lait spots, multiple Turner syndrome—Chromosome abnormality char- raised nodules on the skin known as neurofibromas, acterized by short stature and ovarian failure, developmental delays, slightly larger head sizes, caused by an absent X chromosome. Less common neurologic compli- may have more obvious features of the condition in their cations may include schwannomas, or growths (common childhood photographs. These As of 2001, chest wall abnormalities such as a shield schwannomas may also occur in the muscle. Eyes may be wide-set, may because of early closure of the sutures underneath these appear half-closed because of droopy eyelids, and the areas. Scoliosis (curving of the spine) may occur, as nystagmus and strabismus may occur. Hearing loss may Lymphedema may occur behind the neck (often prena- occur, most often due to frequent ear infections. A very tally) and this is thought to be the cause of the high and broad forehead is very common. As men- phedema is thought to obstruct the proper formation of tioned earlier, facial features may change over time. An the ears, eyes, and nipples as well, causing the mentioned infant may appear more striking than an adult does, as the abnormalities in all three. Parents lems with coagulation, shown by abnormal bleeding or 820 GALE ENCYCLOPEDIA OF GENETIC DISORDERS mild to severe bruising. Careful study would iden- abnormalities in levels of factors V, VIII, XI, XII, and pro- tify Noonan syndrome from these. These problems may lessen hood, however some signs may present in late stages of a as the person ages, even though the mentioned coagula- pregnancy. Lymphedema, cystic hygroma, and heart tion proteins may still be present in abnormal amounts. With high-resolution technology, occasionally some Kidney problems are often mild, but can occur. After such findings, most common finding is a widening of the pelvic (cup- an amniocentesis would typically be offered (as Turner shaped) cavity of the kidney. In males, smaller penis size syndrome would also be suspected) and a normal kary- and cryptorchidism are sometimes seen. It is not as Treatment and management common to see an affected man have a child with Noonan syndrome, and this is probably due to cryptorchidism. Treatment is very symptom-specific, as not everyone Puberty may be delayed in some women with NS1, but will have the same needs. The exact cause of the short stature is not well defined, and therapies Lastly, follicular keratosis is common on the face are currently being studied. It is a set of dark birthmarks that often show delays often necessitate an early intervention program, up during the first few months of life, typically along the which combines physical, speech, and occupational thera- eyebrows, eyes, cheeks, and scalp. Heart defects need to be closely followed, and treat- gresses until puberty, then stops. Sometimes it may leave ment can sometimes include beta-blockers or surgeries, scars, which may prevent hair growth in those areas. For individuals café-au-lait spots can occur, not unlike those seen in neu- with clotting problems, aspirin and medications containing rofibromatosis. Treatments using various blood factors may be necessary to help with Diagnosis proper clotting. Drainage may be necessary for problem- As of 2001, there are no molecular or biochemical atic lymphedema, but it is rare.

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Although the idea of replacement therapy should be started at low initial combining T and T in replacement therapy so as to doses cheap 100 mg extra super levitra with amex, followed by slow titration to full replacement as 4 3 mimic the normal ratio secreted by the thyroid gland is tolerated over several months extra super levitra 100 mg cheap. If hypothyroidism and not new buy 100 mg extra super levitra mastercard, it does not appear that liotrix offers any thera- some degree of adrenal insufficiency coexist cheap 100 mg extra super levitra visa, an appro- peutic advantage over levothyroxine alone. This prevents acute adrenocortical insufficiency Thyroid USP and Thyroglobulin that could otherwise arise from a thyroid hormone– Thyroid USP (Thyrar, Thyroid Strong, S-P-T) is derived induced increase in the metabolic clearance rate of from dried and defatted thyroid glands of domestic an- adrenocortical hormones. Functional autonomy of the nodules develops hormone to patients with coronary artery disease may over time by an unknown mechanism and causes the increase the risk of coronary insufficiency. These autonomously secreting tu- therapy in patients with diabetes mellitus may increase mors occur in an intrinsically normal thyroid gland and the requirement for insulin or oral hypoglycemic result from point mutations in the TSHRs on thyroid agents. Tumor growth is progressive over many years, and with growth, a progressively larger share of thyroid hormone secretion is assumed by the adenoma; TSH secretion is inhibited, while the remainder of the gland is unstimu- THYROTOXICOSIS lated and may atrophy. Continued autonomous growth Thyrotoxicosis is any condition in which the body tis- results in excessive secretion of T4 and T3 and thyrotox- sues are exposed to supraphysiological concentrations icosis. This designation is preferred to the term hyperthyroidism to describe this disorder be- Clinical Manifestations of Thyrotoxicosis cause its origin may not result from excessive thyroid gland secretion. Thyrotoxicosis factitia arises from the The signs and symptoms of thyrotoxicosis, regardless of ingestion of excessive quantities of thyroid hormone the cause, may include the following: increased basal rather than from overactivity of the thyroid gland. The metabolic rate, heat intolerance, tachycardia, widened term hyperthyroidism is reserved for disorders that re- pulse pressure, cardiac arrhythmias, skeletal muscle sult from overproduction of hormone by the thyroid it- weakness, muscle wasting, tremor, hyperreflexia, emo- self. This distinction is important because only condi- tional instability, nervousness, insomnia, change in men- tions caused by hyperthyroidism respond to treatment strual pattern, frequent bowel movements (occasionally with agents that decrease iodine uptake, thyroid hor- diarrhea), and weight loss despite an increased appetite. These ocular manifestations appear to be due presence or absence of extrathyroidal manifestations, largely to increased adrenergic stimulation and are and the specific disorder producing the thyrotoxicosis. In these patients, serum concentrations of T4,T,3 and TSAB are elevated, while TSH levels are sup- Thyrotoxic crisis, thyroid storm, or accelerated hyper- pressed. Thyroid storm is ent until the preexisting intrathyroidal store of thyroid usually abrupt in onset and occurs in patients whose pre- hormone is depleted. Thyrotoxic crisis may be related to cytokine re- Tapazole) are the most commonly used preparations in lease and an acute immunological disturbance caused by the United States. In the thyroid gland, they inhibit Although the serum thyroid hormone levels may not be the activity of the enzyme TPO, which is required for appreciably greater than those in uncomplicated thyro- the intrathyroidal oxidation of I, the incorporation of toxicosis, the clinical picture is severe hypermetabolism I into Tg, and the coupling of iodotyrosyl residues to with fever, profuse sweating, tachycardia, arrhythmias, form thyroid hormones. With progression of the disorder, apa- Propylthiouracil, but not methimazole, also inhibits D1, thy, stupor, and coma may supervene, and hypotension which deiodinates T4 to T3. There are no foolproof criteria by which se- action, propylthiouracil is often used to provide a rapid vere thyrotoxicosis complicated by some other serious alleviation of severe thyrotoxicosis. In any event, the differentiation amide drugs may also exert an immunosuppressive ef- between these alternatives is of no great significance be- fect. As the drug is concentrated in thyroid follicular cause treatment of the two is the same, directed at sys- cells, the expression of thyroid antigen and the release temic support and amelioration of the thyrotoxicosis. Thion- amides also inhibit the generation of oxygen radicals in T cells, B cells, and particularly the antigen-presenting DRUGS USED IN THE TREATMENT cells within the thyroid gland. Thus, thionamides may OF HYPERTHYROIDISM cause a decline in thyroid autoantibody titers, although Treatment of hyperthyroidism is directed at reducing the clinical importance of immunosuppression is un- the excessive synthesis and secretion of thyroid hor- clear. This may be accomplished by inhibiting thy- Thionamide drugs are well absorbed from the gas- roidal synthesis and secretion with antithyroid drugs, by trointestinal tract. Although they have short plasma reducing the amount of functional thyroid tissue, or by half-lives (propylthiouracil 1. Unfortunately, only a small proportion of patients hours), they accumulate in the thyroid gland, and a sin- treated with antithyroid drugs obtain long-term remis- gle daily dose may exert effects for greater than 24 sion of their hyperthyroidism. Since many of the signs and symptoms of hy- form glucuronides and are excreted in the bile and perthyroidism reflect increased cellular sensitivity to urine. Nevertheless, few glucuronide conjugates are adrenergic stimulation, a -adrenergic antagonist is of- found in the feces because they are absorbed from the ten used adjunctively. It of hyperthyroidism and thyrotoxic crisis and in the may reduce thyrotoxicosis-induced tachycardia, palpita- preparation of patients for surgical subtotal thyroidec- tions, tremor, sweating, heat intolerance, and anxiety, tomy. Although the use of thionamides alone may re- which are largely mediated through the adrenergic store euthyroidism, it is difficult to adjust the dosage in nervous system. The use of propranolol is contraindi- and-replace regimens in which a full blocking dose of cated in thyrotoxic patients with asthma or chronic thionamide plus a levothyroxine supplement is pre- obstructive pulmonary disease because it impairs bron- scribed.

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Low-grade malignant neoplasms have all the inva- sive properties of a high-grade lesion but order extra super levitra 100mg free shipping, because the lesions enlarge slowly 100 mg extra super levitra fast delivery, they tend to cross compartmental boundaries slowly rather than destroy them rapidly discount 100 mg extra super levitra with visa. In soft tissues extra super levitra 100 mg discount, stage I lesions often are superficial, nontender, and have few surrounding inflammatory signs. Isotope scans show an area of uptake larger than expected but within the com- partment of origin. There is a surrounding pseudo- capsule composed of compressed reactive tissue that contains micro- scopic foci of tumour (ªsatelliteº lesions). Stage IB, low-grade malignant, extracompartmental (G,T,M)1 2 0 The clinical findings of extracompartmental low-grade malignant tu- mours are similar to those of intracompartmental low-grade malignant tumours. Low-grade lesions may become extracompartmental by direct spread, not responding to the normal inhibitors of tumour growth. An adamantinoma arising in the tibia that violates the anterior cortex and enters the anterior compartment of the lower leg, for example, would be considered stage IB. Because of the inherent lack of effective barriers to tumour spread, the anatomic location may define the lesions as extra- compartmental ±i. Previous surgery contaminates multiple compartments, rendering previously intracompartmental low- grade malignant neoplasms extracompartmental. Radiographic staging studies identify the extracompartmental spread or anatomic location of the primary lesion. High-grade le- sions grow rapidly and appear to have no biologic constraints to growth. Only high-grade malignant lesions discovered very early in their course are intracompartmental. They generally are located deep to the fascia and are fixed to surround- ing tissues. High-grade lesions are poorly marginated on conventional radio- graphs (Lodwick III). Occasionally, matrix formation may give an important clue as to the histogenesis of the lesion. Isotope scans typically show increased uptake in an area much greater than expected based on plain films. The reactive zone must be within the compartment of origin for the tumour to be classified as intracompartmental. Stage IIB, high-grade malignant, extracompartmental (G,T,M)2 2 0 Most high-grade malignant sarcomas present as stage IIB. High-grade lesions are aggressive and quickly extend beyond their compartment of origin. Radiologically, bone lesions are characterized by cortical destruction and early soft-tissue extension. The periosteal reaction often is obliter- ated by the rapid growth and destruction of the tumour. Just as in low-grade lesions, high-grade neoplasms may be extracompartmental by virtue of their anatomic location or previous surgical intervention. Histologically, stage IIB lesions resemble stage IIA lesions, with all of the characteristics of high-grade malignancies. Stage III lesions may be high grade or low grade, extracompartmental or in- tracompartmental. The clinical behaviour and histologic appearance of the primary lesions are similar to corresponding lesions without metas- tases. MR imaging in the longitudinal plane may demon- strate skip metastases may be discovered on physical examination. The lines were evaluated according to their presence or absence, location, and thickness. To combine the data on lucent lines, their extent and thickness, and the data on shift and component position, the authors selected a set of changes that orthopaedic surgeons would, in their opinion, agree were worrisome for component loosening and could be associated with clini- Fig. The authors designated these combinations as represent- ing components radiographically ªat riskº for clinically symptomatic component loosening.

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