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By O. Makas. Illinois State University.

They form the lateral tip of the lemniscus in the midbrain and ter- Aberrant fibers (Déjérine) (A1) order levitra soft 20mg erectile dysfunction causes prescription drugs. At various minatein thesuperior colliculi (pupillary re- levels of the midbrain and the pons buy discount levitra soft 20 mg on line erectile dysfunction treatment brisbane, fine flex on sensation of pain). Anterior tegmental fasciculus (Spitzer) clear fibers and unite to form the mesen- (B10). The fibers (protopathic and epicritic cephalic aberrant tract and the pontine aber- sensibilities of the face) cross in small rant tract. Both descend in the medial lem- bundles from the spinal nucleus of the niscus (A2) and terminate in the con- trigeminal nerve (principle nucleus) to the tralateral abducens nucleus (VI) and hypo- contralateral side (trigeminal lemniscus) glossal nucleus (XII), in the two ambiguous and join the medial lemniscus at the level of nuclei (X), and in the spinal accessory nu- the pons. These origi- Medial Lemniscus (B) nate from the rostral part of the solitary nu- cleus (B12), probably cross to the con- This fiber system includes the most impor- tralateral side, and occupy the medial mar- tant ascending pathways of the exteroceptive gin of the lemniscus. It is subdivided into the spinal lemnis- cus and the trigeminal lemniscus. The spinal lemniscus contains the sensory pathways Kahle, Color Atlas of Human Anatomy, Vol. Pyramidal Tract System, Medial Lemniscus 141 III III 2 IV IV V V VI 1 VII VII 11 10 9 X X XII 8 3 11 XI XI 12 A Pyramidal system: corticospinal tract and corticonuclear fibers 10 8 3 7 6 5 B Ascending pathways of the medial lemniscus 4 Kahle, Color Atlas of Human Anatomy, Vol. It reaches from the rostral midbrain into the spinal cord and interconnects numerous nuclei of the brain stem. On cross Internuclear Connections of the sections through the brain stem, it is found Trigeminal Nuclei in the middle of the tegmentum, ventrally Only a few secondary trigeminal fibers en- from the central gray (p. Crossed and uncrossed in the dorsolateral region of the tegmentum fibers run in the longitudinal fasciculus to the motor nuclei of cranial nerves; they from the lateral (A1), medial (A2), and infe- form the basis of numerous important re- rior (A3) vestibular nuclei to the abducens flexes. Crossed and uncrossed fibers run to nucleus (A4) and to the motor cells of the the facial nucleus as the basis of the corneal anterior horn of the cervical spinal cord. There are connections to the superior fibers ascend to the ipsilateral trochlear nu- salivatory nucleus for the lacrimal reflex. Fibers to the hypoglossal nucleus, to the The vestibular fibers finally terminate in the ambiguous nucleus, and to the anterior ipsilateral or contralateral interstitial nu- horncellsofthecervicalspinalcord(cellsof cleus of Cajal (A8) and in Darkshevich’s nu- origin of the phrenic nerve) are the basis of cleus (A9) (decussation of the epithalamic the sneezing reflex. The longitudinal based on fiber connections to the ambigu- fasciculus connects the vestibular apparatus ous nucleus, the posterior vagus nucleus, with the eye and neck muscles and with the and the motor nucleus of the trigeminal extrapyramidal system (p. Connections with the posterior vagus nucleus are the basis of the oculocardial re- Extrapyramidal part. The interstitial nu- flex (slow heart rate upon pressure on the cleus of Cajal and Darkshevich’s nucleus are eyeballs). They receive fibers from the striatum and pallidum and crossed fibers from the cerebellum. They send a fiber tract, the interstitiospinal fasciculus (A11), in the longitudinal fasciculus to the caudal brain stem and into the spinal cord. This consists of connect- ing fibers between motor nuclei of cranial nerves, namely, between abducens nucleus (A4) and oculomotor nucleus (A7), facial nucleus (A12) and oculomotor nucleus, fa- cial nucleus and motor nucleus of the trigeminal nerve (A13), hypoglossal nucleus (A14) and ambiguous nucleus (A15). The interconnections of motor nuclei of cranial nerves allow certain muscle groups to interact functionally, for example, during the coordination of eye muscles with the Kahle, Color Atlas of Human Anatomy, Vol. Medial Longitudinal Fasciculus 143 10 9 8 7 6 13 4 12 5 2 1 3 14 15 11 A Medial longitudinal fasciculus (ac- cording to Crosby, Humphrey, and Lauer) Kahle, Color Atlas of Human Anatomy, Vol. They originate or terminate, respec- The central tegmental tract is the most im- tively, in the septum, the oral hypothalamus, portant efferent pathway of the extrapy- the gray tubercle (B13), and the mamillary ramidal motor system (p. They aggregate in the mid- the midbrain to the lower portion of the brain below the ependyma (p. The remaining fibers are thought fasciculus, which runs beneath the to continue into the spinal cord via short ependyma on the floor of the fourth ven- neurons that synapse in series (reticuloretic- tricle to the lower portion of the medulla ular fibers) (A2). The pallido-olivaryfibers (A3) from the stri- vatory nuclei, and the posterior vagus nu- atum (A4) and the pallidum (A5), which cleus (B19). Other fibers terminate in the extend in the pallidotegmental bundle cranial nerve nuclei, namely, in the motor (A6) to the capsule of the red nucleus nucleus of the trigeminal nerve (B20), the fa- (A7) and further to the olive.

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Outcome: the reference standard Principles Establishing a final and “gold standard” diagnosis of the target disorder is generally more invasive and expensive than applying the studied diagnostic 47 THE EVIDENCE BASE OF CLINICAL DIAGNOSIS test cheap levitra soft 20mg online erectile dysfunction dsm 5. It is exactly for this reason that good test accuracy (for example a very high sensitivity and specificity) would be very useful in clinical practice to make a satisfactory diagnostic assessment without having to perform the reference standard cheap 20mg levitra soft with mastercard erectile dysfunction kidney transplant. However, in performing diagnostic research the central outcome variable – the presence or absence of the target disorder – must be measured, as it is the reference standard for estimating the test accuracy. A real gold – that is, perfect – standard test, with 100% sensitivity and specificity, is exceptional. Even histological classification and MRI imaging are not infallible, and may yield false positive, false negative and uninterpretable conclusions. Therefore, the term “reference standard” is nowadays considered better than “gold standard”. Applying different standard proce- dures for different patients may yield an inconsistent reference for the evaluated test, as each of the “standards” will have its own idiosyncratic error rate. The results of the test for each patient should be interpreted without knowledge of the reference standard results. Similarly, the reference standard result should be established without knowing the outcome of the test under study. Where such blinding is not maintained, “test review bias” 48 ASSESSING THE ACCURACY OF DIAGNOSTIC TESTS and “diagnosis review bias” may occur: non-independent assessment of test and reference standard, mostly resulting in overestimation of test accuracy. The reference standard must be properly performed and interpreted using standardised criteria. This is especially important when the standard diagnosis depends on subjective interpretations, for example by a psychiatrist, a pathologist, or a radiologist. In such cases inter- and even intraobserver variability in establishing the standard can occur. For example, in evaluating the intraobserver variability of MRI assessment as the standard for nerve root compression in sciatica patients, the same radiologist repeatedly scored the presence of root compression as such consistently ( : 1. Problems and solutions Apart from the limitations in reaching a 100% perfect standard diagnosis, meeting the requirements for a reference standard can be problematic in various ways. For many conditions a reference standard cannot be measured on the basis of a well defined pathophysiological concept, independent of the clinical presentation. Examples are sinusitis, migraine, depression, irritable bowel syndrome, and benign prostatic hyperplasia. When, in such cases, information related to the test result (for example symptom status) is incorporated into the diagnostic criteria, “incorporation bias” may result in overestimation of test accuracy. Furthermore, a defined reference standard procedure may sometimes be too invasive for research purposes. For instance, when validating urinary flow measurement it would be unacceptable to apply invasive urodynamic studies to those with normal flow results. Another problem can be that a complex reference standard might include a large number of laboratory tests, so that many false positive test results could occur by chance. Pragmatic criteria The absence of a well defined pathophysiological concept can sometimes be overcome by defining consensus based pragmatic criteria. However, if applying such reference standard criteria (such as a cut-off value on a 49 THE EVIDENCE BASE OF CLINICAL DIAGNOSIS depression questionnaire) is no more difficult than applying the test under study, evaluating and introducing the test will not be very useful. Independent expert panel Another method is the composition of an independent expert panel that, given general criteria and decision rules for clinical agreement, can assign a final diagnosis to each patient, based on the available clinical information. To achieve a reasonably consistent classification it is important that the panel is well prepared for its task, and a training session or pilot study using patients with an already established diagnosis is recommended. The agreement of the primary assessments of the individual panel members, prior to reaching to consensus, can be documented. Clinical follow up: delayed-type cross-sectional study When applying a definitive reference standard is too invasive or otherwise inapplicable at the very moment that the test should be predictive for the presence of the target disorder, a good alternative can be follow up of the clinical course during a suitable predefined period. Most diseases that are not self-limiting, such as cancers and chronic degenerative diseases, will usually become clinically manifest a period of months or a year or so after the first diagnostic suspicion (generally the moment of enrolment in the study) was raised.

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Constriction of the superficial that any osmotic imbalance between the intracellular and limb veins further improves heat conservation by diverting extracellular compartments is rapidly corrected by the venous blood to the deep limb veins cheap 20 mg levitra soft overnight delivery impotence at 46, which lie close to the movement of water across the cell membranes (see Chapter major arteries of the limbs and do not constrict in the cold effective 20mg levitra soft erectile dysfunction essential oils. Effect of Sweat Secretion on Body Fluid Compartments and Plasma Sodium Concentrationa TABLE 29. The sweat of subject A has a relatively high [Na ] of 60 mmol/L while that of subject B has a relatively low [Na ] of 10 mmol/L. Volumes of the extracellular and intracellular spaces are calculated assuming that water moves between the two spaces as needed to maintain osmotic balance. Water loss via the cellular fluid, and by decreased plasma volume via a reduc- sweat glands can exceed 1 L/hr for many hours. Salt loss in tion in the activity of the cardiovascular stretch receptors the sweat is variable; however, since sweat is more dilute (see Chapter 18). When sweating is profuse, however, thirst than plasma, sweating always results in an increase in the usually does not elicit enough drinking to replace fluid as osmolality of the fluid remaining in the body, and in- rapidly as it is lost, so that people exercising in the heat tend creased plasma [Na ] and [Cl ], as long as the lost water is to become progressively dehydrated—in some cases losing not replaced. By contrast, the fourth and fifth condi- mally hydrated but hyponatremic, or somewhat dehydrated tions (subject B) represent the corresponding effects for a with plasma [Na ] anywhere in between these two ex- heat-acclimatized person secreting dilute sweat. Once subject A replaces all the water lost as sweat, ing the effects on these two individuals, we note: (1) The his extracellular fluid volume will be about 10% below its ini- more dilute the sweat that is secreted, the greater the in- tial value. If he responds to the accompanying reduction in crease in osmolality and plasma [Na ] if no fluid is re- plasma volume by continuing to drink water, he will be- placed; (2) Extracellular fluid volume, a major determinant come even more hyponatremic than shown in Table 29. Greater disturbances, with corre- plain water allowed subject B to maintain plasma sodium spondingly more severe clinical effects, may occur. The and extracellular fluid volume almost unchanged while se- consequences of the various possible disturbances of salt creting 5 L of sweat. In subject A, however, drinking the and water balance can be grouped as effects of decreased same amount of water reduced plasma [Na ] by 8 mmol/L, plasma volume secondary to decreased extracellular fluid and failed to prevent a decrease of almost 10% in extracel- volume, effects of hypernatremia, and effects of hypona- lular fluid volume. As the blood vessels in the shell constrict, blood the deep veins, so that venous blood from anywhere in the is shifted to the central blood reservoir in the thorax. This limb potentially can return to the heart via either superficial shift produces many of the same effects as an increase in or deep veins. Therefore, some of the Once skin blood flow is near minimal, metabolic heat heat contained in the arterial blood as it enters the limbs production increases—almost entirely through shivering takes a “short circuit” back to the core. Shivering may increase metabolism at rest blood reaches the skin, it is already cooler than the core, so by more than 4-fold—that is, to 350 to 400 W. Nonshivering thermogenesis ap- cool but comfortable subject to as low as 30 C by the time pears to be elicited through sympathetic stimulation and it reaches the wrist. It occurs in many tissues, espe- As we saw earlier, the shell’s insulating properties increase cially the liver and brown fat, a tissue specialized for non- in the cold as its blood vessels constrict and its thickness in- shivering thermogenesis whose color is imparted by high creases. Furthermore, the shell includes a fair amount of concentrations of iron-containing respiratory enzymes. In a cool subject, the resulting The existence of brown fat and nonshivering thermogene- reduction in muscle blood flow adds to the shell’s insulating sis in human adults is controversial, but there is some evi- The circulatory effects of decreased volume are causes symptoms. The development of water intoxication nearly identical to the effects of peripheral pooling of requires either massive overdrinking, or a condition, such blood (see Fig. These effects include im- drinking sufficient to cause hyponatremia may occur in pa- pairment of cardiac filling and cardiac output, and com- tients with psychiatric disorders or disturbance of the thirst pensatory reflex reductions in renal, splanchnic, and mechanism, or may be done with a mistaken intention of skin blood flow. Impaired cardiac output leads to fatigue preventing or treating dehydration. However, individuals during exertion and decreased exercise tolerance; if skin who secrete copious amounts of sweat with a high sodium blood flow is reduced, heat dissipation will be impaired. Myoglobin released from injured skeletal mus- come to medical attention for salt depletion after profuse cle cells appears in the plasma, rapidly enters the sweating are found to have genetic variants of cystic fibro- glomerular filtrate, and is excreted in the urine, produc- sis, which cause these individuals to have salty sweat with- ing myoglobinuria and staining the urine brown if out producing the characteristic digestive and pulmonary enough myoglobin is present. Most of the manifestations of hy- Hypernatremic dehydration is believed to predis- ponatremia are due to the resulting swelling of the brain pose to heatstroke. Mild hyponatremia is characterized by nonspecific both hypernatremia and reduced plasma volume.

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Nerves emerging from the plexuses are named nerves to supply dual innervation to some specific neck and pha- according to the structures they innervate or the general course ryngeal muscles (see fig generic levitra soft 20mg online erectile dysfunction protocol reviews. Peripheral Nervous © The McGraw−Hill Anatomy purchase levitra soft 20 mg otc erectile dysfunction treatment penile implants, Sixth Edition Coordination System Companies, 2001 416 Unit 5 Integration and Coordination TABLE 12. Motor impulses through fibers from the anterior branches of spinal nerves C5 through the paired phrenic nerves cause the diaphragm to contract, mov- T1 and a few fibers from C4 and T2. The roots converge to form trunks, and The nerves of the cervical plexus are summarized in the trunks branch into divisions. Brachial Plexus The brachial plexus may suffer trauma, especially if the clavi- cle, upper ribs, or lower cervical vertebrae are seriously frac- The brachial plexus is positioned to the side of the last four cer- tured. Occasionally, the brachial plexus of a newborn is severely vical vertebrae and the first thoracic vertebra. It is formed by the strained during a difficult delivery when the baby is pulled through anterior rami of C5 through T1, with occasional contributions the birth canal. In such cases, the arm of the injured side is para- lyzed and eventually withers as the muscles atrophy in relation to the from C4 and T2. Each brachial plexus innervates called a brachial block or brachial anesthesia. The site for injection of the entire upper extremity of one side, as well as a number of the anesthetic is located midway between the base of the neck and the shoulder, posterior to the clavicle. Structurally, the brachial plexus is divided into roots, trunks, divisions, and cords (figs. The roots of Five major nerves—the axillary, radial, musculocutaneous, the brachial plexus are simply continuations of the anterior rami ulnar, and median—arise from the three cords of the brachial of the cervical nerves. The anterior rami of C5 and C6 converge plexus to supply cutaneous and muscular innervation to the to become the superior trunk, the C7 ramus becomes the mid- upper extremity (table 12. The axillary nerve arises from the dle trunk, and the ventral rami of C8 and T1 converge to be- posterior cord. It provides sensory innervation to the skin of the come the inferior trunk. Each of the three trunks immediately shoulder and shoulder joint, and motor innervation to the del- divides into an anterior division and a posterior division. The posterior cord from the posterior cord and extends along the posterior aspect of is formed by the convergence of the posterior divisions of the the brachial region to the radial side of the forearm. It provides upper, middle, and lower trunks; hence, it contains fibers from sensory innervation to the skin of the posterior lateral surface of C5 through C8. The medial cord is a continuation of the ante- the upper extremity, including the posterior surface of the hand rior division of the lower trunk and primarily contains fibers from (fig. The lateral cord is formed by the convergence of the of the elbow joint, the brachioradialis muscle that flexes the anterior division of the upper and middle trunk and consists of elbow joint, and the supinator muscle that supinates the forearm fibers from C5 through C7. Peripheral Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Chapter 12 Peripheral Nervous System 417 FIGURE 12. Cervical plexus region Deltoid muscle Brachial plexus region Musculocutaneous nerve Brachiocephalic artery Median nerve Subclavian artery Ulnar nerve Medial pectoral nerve Medial antebrachial cutaneous nerve Pectoralis major muscle Thoracodorsal nerve Serratus anterior muscle Latissimus dorsi muscle FIGURE 12. Peripheral Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 TABLE 12. Peripheral Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Chapter 12 Peripheral Nervous System 419 Posterior cord of Posterior cord of Lateral cord of brachial plexus brachial plexus brachial plexus Medial cord of Lateral cord of brachial plexus brachial plexus Medial cord of brachial plexus Musculocutaneous nerve Biceps brachii m. Crutch The motor innervation of the ulnar nerve is to two muscles of paralysis may result when a person improperly supports the the forearm and the intrinsic muscles of the hand (except some weight of the body for an extended period of time with a crutch pushed tightly into the axilla. Likewise, dislocation of the shoulder frequently traumatizes the The ulnar nerve can be palpated in the ulnar sulcus between radial nerve. Children are particularly at risk as adults yank on their the medial epicondyle of the humerus and the olecranon of arms. A fracture to the body of the humerus may damage the radial the ulna (see fig. This area is commonly known as the “funny nerve, which parallels the bone at this point. As a result, the joints of the fingers, perception of this trauma is a painful tingling that extends down the wrist, and elbow are in a constant state of flexion. It provides sensory innervation to the skin of the posterior lat- The median nerve arises from the medial cord. It provides eral surface of the arm and motor innervation to the anterior sensory innervation to the skin on the radial portion of the palm muscles of the brachium (fig.

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