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Four conditions are possible generic lasix 40 mg arrhythmia upon waking, only one of which (agonist site occupied order 40 mg lasix amex heart attack burger, antagonist site empty; see upper right) is active discount lasix 40 mg on-line hypertensive urgency guidelines. In the presence of a large enough concentration of such an antagonist generic 100 mg lasix visa blood pressure chart readings for ages, the inhibition will become insurmountable; too few receptors remain free of antagonist to give a full response, even if all the agonist sites are occupied. The point at which this occurs in a particular tissue will depend on the numbers of spare receptors, just as with an irreversible competitive antagonist (see Section 1. If a full agonist is used and the tissue has a large receptor reserve, the initial effect of a reversible noncompetitive antagonist will be to shift the log concentration–response curve to the right. In contrast, without a receptor reserve, the antagonist will depress the maximum from the outset. For (A), the response has been assumed to be directly proportional to the fraction of receptors in the active state. This condition has been modeled by supposing that the relationship between the response, y, and the proportion of active receptors is given by y = 1. In A, the response has been assumed to be directly proportional to pactive; there are no spare receptors. In B, spare receptors have been assumed to be present, and accordingly the presence of a relatively low concentration of the antagonist causes an almost parallel shift before the maximum is reduced. If we consider the two concentrations of agonist that give equal responses before and during the action of the antagonist ([A] and r[A], respectively, where r is the concentration ratio) and repeat the derivation set out in Section 1. The vertical arrows show the concentrations of agonist causing a half-maximal response in the absence and presence of C at 50 µM. A corollary is that a demonstration of the Schild equation holding over a small range of concentrations should not be taken as proof that the action of an antagonist is competitive. Clearly, as wide as practicable a range of antagonist concentrations should be tested, especially if there is evidence for the presence of spare receptors. Open Channel Block Studies of the action of ligand-gated ion channels have brought to light an interesting and important variant of reversible noncompetitive antagonism. It has been found that some antagonists block only those channels that are open by entering and occluding the channel itself. Such antagonists cause a characteristic change in the log concentration–response curve for an agonist. In contrast to what is observed with the other kinds of antagonism so far considered, the value of [A]50 will become smaller rather than larger in the presence of the antagonist. Note, too, the convergence at low agonist concentrations of the curves plotted in Figure 1. Again, in contrast to the other kinds of antagonism that have been described, there is no initial parallel displacement of the curves (even if many spare receptors are present), and the Schild equation is never obeyed. Some antagonists combine the ability to block open ion channels with a competitive action at or near the agonist binding site. A well-characterized example is the nicotinic blocker tubocurarine (see Chapter 6). Agonists may also be open channel blockers, thus limiting the maximal response that they can elicit. Glutamate is then referred to as the primary agonist, and glycine as a co- agonist. In principle, an antagonist could act by competing with either the primary agonist or the co-agonist. Two ligands, A and B, can bind to different sites on the receptor so that in principle both can be present at the same time, as shown in Figure 1. The underlying concept is that any substance that combines with an accessory (allotopic, allosteric) site can be expected to alter the equilibrium between the active and inactive states of the receptor and so affect agonist action. Each supposes that A is a conventional, “positive” agonist; that is, its presence increases the proportion of active receptors because of its preferential affinity for the active form. We suppose that A and B combine with separate sites on the receptor macromolecule, R, so that both can be present at the same time (top edge of the rear face of the cube). Active and inactive states of the receptor are represented by the right- and left-hand side faces respectively. If, in addition, the affinity of B for the active form of the receptor is very low, B will then act as a competitive antagonist (see Figure 1. Under these circumstances, B acts as a co-agonist for A; full activation requires the simultaneous presence of A and B (see Figure 1. To denote either a binding site other than that for the agonist or a ligand that acts by combining with this other site. For example, the “allosteric antagonist” gallamine influ- ences activation of the muscarinic receptor by binding to a distinct region (an “allosteric * Here, competitive is defined as in Section 1. Each panel illustrates the effect of the additional ligand, B, at the four concentrations (µM) indicated by the number given with each line. For panels A, B, and C, but not D, the agonist has been assumed to have a high intrinsic efficacy so that almost all of the receptors can be activated by it. An additional assumption throughout is that the constitutive activity of the receptor is low, so that in the absence of ligands, few of the receptors are active. Here, the second ligand, B, has been assumed to have a high preferential affinity for the inactive forms of the receptor. The two ligands A and B have been assumed to combine with the receptor in an almost mutually exclusive manner. In effect, A and B are in competition, and the model then predicts that increasing concen- trations of B cause a near-parallel shift in the curves.

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This both the neuropathologic and behavioral changes monkey species develops cerebral amyloid plaques that these mice develop cheap 40mg lasix amex hypertension 2 torrent. Immunized or passive transfer with Aβ antibodies has been animals generated anti-Aβ antibodies that labeled shown to prevent and reduce the cerebral amyloid Aβ plaques in human lasix 100mg online heart attack feat thea austin, transgenic mouse order 40mg lasix fast delivery hypertension 90, and load [9 purchase lasix 40mg amex blood pressure chart graph, 36, 37]. This find- plete or incomplete Freund`s adjuvant, almost com- ing confirms that Aβ can be moved from the cen- pletely prevented plaque deposition when given tral to peripheral compartment where the anti-Aβ before initiation of plaque formation and signifi- antibodies bind them, enhancing clearance of Aβ cantly lowered cerebral levels if given after the initi- [46]. Evidence has been provided that the antibod- ticular, no Aβ-reactive T-cell populations were ies generated by active immunization with Aβ pep- detected. Karkos Plaque clearance can be invoked only by anti- native clearing mechanisms should be taken in bodies against epitopes located in the N-terminal consideration. It has also been shown that the Mechanisms by which antibodies act are not isotype of the antibody prominently influences the entirely understood. For example, IgG2a include (i) microglial-mediated phagocytosis (Fc- antibodies against Aβ were more efficient that dependent, Fc-independent, or combination of Fc- IgG1 or IgG2b antibodies in reducing pathology. They are likely to be synergistic if mul- deposits, which appears to require microglial acti- tiple mechanisms are elicited by a single antibody vation. Other possible mechanisms of amyloid with dexamethasone, administration of anti-Aβ removal would include activation of scavenger antibody inhibited the removal of compact, receptors [61, 62] or receptors for advanced glyca- thioflavine-S-positive amyloid deposits [54]. This group also showed that passive immuniza- resulted in a twofold increase in the rate of hemor- tion improved behavioral performance. To better understand this potential side improvement might reflect rapid reduction of the effect, Racke et al. It was shown that IgG2a antibodies whether the amyloid angiitis that has been recently are efficacious in clearing fibrillar, thio-S-positive reported [66] would augment the risk of such hem- plaque. Taken together, circulating antibodies consistent with their ability to best stimulate elicited by active immunization or administered microglial and peripheral macrophage phagocyto- passively cross the blood-brain barrier [67, 68]. This finding also supports a crucial role for Moreover, administration to transgenic animals of microglial Fc receptor-mediated phagocytosis in monoclonal Aβ antibodies against defined Aβ epi- the clearance of at least fibrillar plaques. However, topes reduces plaque burden and improves cogni- because Fc knockout mice show a reduction of tive deficits to the same degree as active plaque burden after Aβ immunotherapy [57], alter- immunization [8]. Immunotherapeutic Approaches to Alzheimer’s Disease 249 Assessment of morphological and behavioral No treatment differences were observed in three changes in animals is a very important issue for other efficacy measures. Treatment-related side comparative purposes and for effectivity and safety effects were reported in 19 (23. One patient developed menin- may be particularly difficult, because these deficits goencephalitis 219 days after discontinuing from are only in part related to amyloid deposition. The symp- further clarification of potential damage caused by toms and signs of encephalitis included headache, immunization to the cerebral vessels. The majority of patients had IgG the finding that active and passive vaccination responses to Aβ, and all patients mounted at least with Aβ exerts remarkable Aβ-reducing effects in a small IgM response. In some First, the responder population needs to be charac- regions devoid of plaques, Aβ-immunoreactivity terized. Moreover, pathology, only about half of the patients benefit in the neocortical areas devoid of plaques, densities from the treatment. The plaque-associated dystrophic neu- esis of the side effects is definitively determined. At Inflammatory response, demyelination, and intrac- immunohistochemistry, the plaques were sur- erebral bleeding would be severe and intolerable rounded by IgG and C3 complement. Current data indi- cerebral white matter showed marked reduction in cate that the meningoencephalitis may be due to a the density of myelinated fibers and extensive infil- T-cell response rather than the anti-Aβ antibodies. Moreover, cephalitis induced by vaccination with amyloid-β multinucleated giant cells filled with dense Aβ42 peptide should now be possible using a recently and A4β40 were seen. Interestingly, severe small cerebral blood vessel It cannot be excluded that the differences in lesion (lipohyalinosis) and multiple cortical hemor- safety results obtained in transgenic animals and in rhages, including acute lesions and lesions with clinical trials depend, at least to some extent, on the macrophages filled with hemosyderin, were found. Research Plaque associated neuritic dystrophy in the frontal cortex was undetectable. Only minimal lympho- ance of Aβ from the brain is dependent on anti-Aβ cytic reaction was observed in the leptomeninges antibody and not on T cell–mediated mechanisms. Immunotherapeutic Approaches to Alzheimer’s Disease 251 side-effects observed in the first clinical trials. This new class of antibodies appears to rec- the use of humanized monoclonal anti-Aβ anti- ognize a common conformational epitope with lit- bodies will entirely eliminate a cellular response to tle apparent dependence on amino acid side-chain Aβ, with comparable effectiveness to active immu- conformation. The development of new delivery systems Aβ42 by 57% was detected after immunization with can also contribute to the improvement of efficacy a soluble non-amyloidogenic, nontoxic Aβ homol- and safety aspects of immunization. An epitope vaccine has been immunization from both efficacy and safety per- engineered composed of the B-cell epitope from spectives. Particularly, passive immunotherapy the immunodominant region of Aβ42, Aβ1-15 in tan- using a humanized monoclonal anti-Aβ antibody dem with a universal synthetic T-cell epitope, pan will entirely eliminate a cellular response to Aβ. Polyclonal vaccine produced high titers of anti-Aβ antibodies anti-Aβ antibodies can be delivered by healthy [78]. The binding of the antibody achieves its N-terminal regions of Aβ were able to invoke effect by restoring the structural cooperativity char- plaque clearance. This appeared to clearance response, whereas the ability of antibod- occur at least in part through the transmission of ies to capture soluble Aβ was not necessarily cor- long-range conformational effects to the interface related with efficacy. High Ultrastructural investigation into structure of affinity of the antibody for Fc receptors seemed human classical plaques in different stages of more important that high affinity for Aβ itself. In line with these findings, Wyss-Coray observed between antibody-titer and reduced amy- et al. Further- enables intranasal administration without use of more, it was demonstrated [87] that a modest adjuvant [40].

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The object of the injection is to decrease the inflammation in a specific anatomic area best 100mg lasix prehypertension at 24. The majority of cervical spine patients get better and should be encouraged to gradually increase their activities order lasix 100mg overnight delivery 01 heart attackm4a demi. An exercise program should be directed at strengthening the paravertebral musculature 100 mg lasix visa blood pressure chart india, not at increasing the range of motion order lasix 40mg visa hypertension teaching plan. Should regression occur, with exacerbation of symptoms, the physician can resort to more stringent conservative measures. The majority of patients with neck pain will respond to therapy and return to a normal life pattern within 2 months of the beginning of their problem. If the initial conservative treatment regimen fails, symptomatic patients are divided into two groups. The first is composed of people who have neck pain as a predominant complaint, with or without interscapular radiation. Neck Pain Predominant After 6 weeks of conservative therapy with no symptomatic relief, plain roentgenograms with lateral flexion–extension films are carefully exam- ined for abnormalities. In the lower cervical spine (C3 through C7), instability is identified by horizontal translation of one vertebra on another of more than 3. The majority of patients with instability will respond well to further nonoperative measures, including a thorough explanation of the problem and some type of bracing. In some cases, these measures fail and a surgical fusion of the involved spinal segments will be necessary. Another group of patients complaining mainly of neck pain will be found to have degenerative disease on their plain X-ray films. The roent- genographic signs include loss of height of the intervertebral disk space, osteophyte formation, secondary encroachment of the intervertebral foramina, and osteoarthritic changes in the apophyseal joint. The difficulty is not in identifying these abnormalities on the roentgenogram but in determining their significance. In a study of matched pairs of asymptomatic and symptomatic patients, it was concluded that large numbers of asymptomatic patients show roentgenographic evidence of advanced degenerative disease. The most significant roentgenographic finding relevant to symptomatology was found to be narrowing of the intervertebral disk space, particularly between C5–C6 and C6–C7. There was no difference between the two groups insofar as changes at the apophyseal joints, intervertebral foramina, or posterior articular process. These patients should be treated symptomatically with antiinflammatory medication, support, and trigger-point injections as required. Finally, they should be reexamined periodically because some will develop significant pressure on the neurologic elements (myelopathy). The bone scan is an excellent tool, often identifying early spinal tumors or infections not seen on routine roentgenographic examinations. A thorough medical search may also reveal problems missed in the early stages of neck pain evaluation. If the foregoing workup is negative, the patient should have a thorough psycho- social evaluation; this is predicated on the belief that a patient’s disability is related not only to his pathologic anatomy, but also to his perception of 7. The Spine 297 pain and his stability in relationship to his sociologic environment. Drug habituation, alcoholism, depression, and other psychiatric problems are frequently seen in association with neck pain. If the evaluation reveals this type of pathology, proper measures should be instituted to overcome the disability. Should the outcome of the psychosocial evaluation prove to be normal, the patient can be considered to have chronic neck pain. One must be aware that other outside factors such as compensation and/or litigation can influence a patient’s perception of his subjective pain. Patients with chronic neck pain need encouragement, patience, and education from their physi- cians. All these patients need periodic reevaluation to avoid missing any new or underlying pathology. Arm Pain Predominant (Brachialgia) Patients who have pain radiating into their arm may be experiencing their symptoms secondary to mechanical pressure and inflammation of the involved nerve roots. This mechanical pressure may arise from a ruptured disk or from bone secondary to degenerative changes. Extrinsic pressure on the vascular structures or on the peripheral nerves are most likely imitators of brachialgia. If any of these are positive for peripheral pressure on the nerves or other pathology, the appropriate therapy should be administered. It has been repeatedly documented that for surgery to be effective, unequivocal evidence of nerve root compression must be found at surgery. One must have a strong confirmation of mechanical root compression from the neurologic examination and a confirming study before proceeding with any surgery. If the patient does not have these, there is inadequate clini- cal evidence to proceed with surgery. For patients who have met these cri- teria for cervical decompression, the results will usually be satisfactory: 95% of them can expect good or excellent outcomes. Conservative Treatment Modalities Most patients with neck pain will achieve relief from a conscientious program of conservative care. As the algorithm indicates, all patients with either chronic or acute neck pain (except those with severe myelopathy) deserve an initial period of conservative therapy. There are a multitude of treatment modalities available, but many of them are based on empiri- cism and tradition. The purpose of this section is to discuss the rationale behind the use of some of the more common nonoperative therapeutic measures.

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Breast fullness and of the diuretics themselves may be a factor in diuretic subcutaneous swelling or puffiness are the most com- resistance purchase 40 mg lasix with mastercard blood pressure chart based on height and weight. These patients may thus cheap lasix 100 mg blood pressure visual chart, when present in relatively high concentrations generic 100mg lasix overnight delivery blood pressure drops when standing, be vulnerable to ototoxicity or other adverse effects if may produce some expansion of the extracellular fluid larger amounts of the diuretic are employed discount 100 mg lasix amex blood pressure levels in adults. Excessive premenstrual edema fre- Compensatory proximal tubular sodium absorption quently responds well to thiazide therapy. Recent expe- may contribute to or be responsible for the resistance rience has diminished enthusiasm for use of any diuret- to loop diuretics. Since the edema of pregnancy is used as an alternative approach to treating diuretic re- sistance once it has been verified that satisfactory Na frequently well tolerated, concerns of compromised uteroplacental perfusion, possible ineffectiveness of di- restriction is being followed and that the drug is being uretics in preeclampsia, and the risk of adverse effects adequately absorbed. Administration of a carbonic an- hydrase inhibitor may be sufficient to enhance Na de- of diuretics on the baby (e. Alternatively, thiazide newborns) have led to diminished routine use of these diuretics may be combined with the loop diuretic to agents in pregnancy. The thi- azidelike diuretic metolazone, which has some proxi- mal tubule effects unrelated to carbonic anhydrase, ap- Resistance to Diuretic Administration pears to be the most effective of the thiazide and Since the effectiveness of many diuretics ultimately de- thiazidelike drugs in this regard. Therefore, one cause of therapeutic failure or apparent patient refrac- Excessively vigorous diuresis may lead to intravascular toriness to diuretics could be the patient’s continued in- dehydration before removal of edema fluid from the gestion of large quantities of NaC1. This is especially Some of the older diuretic drugs were self-limiting; dangerous if the patient has significant liver or kidney that is, prolonged administration resulted in a gradual disease. This problem was cor- trolyte derangement has been achieved, the effect sought rected through the use of intermittent diuretic therapy. Drug Such a program of several days of diuresis followed by dosage, frequency of administration, and Na intake several days of drug withdrawal delayed refractoriness should be adjusted to achieve homeostasis. Solution Manufacturer Since the 1950s, diuretic therapy has changed dra- Normosol-R Abbott matically. Either because of Polysal Cutter toxicity or lack of efficacy, these agents are rarely if Lactated Ringer’s (Several) ever used. Most of these solutions contain electrolytes in the following mEq range: sodium (130–150), potassium (4–12), chloride (98–109), bi- carbonate (50–55), calcium (3–5), and magnesium (0–3). The beneficial effect of the sustained (A) Na reduction of blood pressure is due to reduced vascu- (B) K lar resistance. Extracellular volume remains modestly (C) Ca and Mg reduced and cardiac output returns to pretreatment (D) Uric acid levels. Which of the following drugs is an appropriate ini- and is associated with an increased risk of ventricular tial antihypertensive therapy in an otherwise fibrillation and malignant arrhythmias. However, the degree to (B) Triamterene which individual patients are affected varies, though (C) Hydrochlorothiazide chronic administration of even small doses causes (D) Aldactone some K depletion. One is competition of the thiazide class of pulmonary edema, there is often symptomatic relief diuretics, which are weak organic acids, with uric acid within 5 minutes of starting treatment. Serum concentrations of (A) A rapid diuretic effect uric acid are further elevated by the reduced extracel- (B) An increase in venous capacitance lular volume. Diuretic-induced hyperuricemia may (C) A direct effect on myocardial contractility cause acute gouty attacks. The use of diuretics in congestive heart fail- acid excretion decreases as a consequence of com- ure. Clinical complications of diuretic ther- of a thiazide diuretic for monotherapy has been rec- apy. Diuretic drugs and the treatment of Detection, Evaluation and treatment of High Blood edema: From clinic to bench and back again. Diuretics in cardiovascular However, thiazide diuretics are a more conservative therapy: the new clinicopharmacological bases that and approved approach for the initial treatment of matter. Metolazone would be expected to be very effec- tive, particularly in combination with a loop diuretic. Case Study Furosemide Resistance A 26-year-old woman with nephrotic syn- (C) Sequestration of furosemide by intraluminal al- Adrome comes to your office because of wors- bumin thereby reducing its inhibition of the ening edema. On physical examination, her blood to the thick ascending limb of Henle’s loop pressure is 120/85 mm Hg, and she has generalized (E) All of the above massive edema (anasarca). Availability at the luminal site depends on the 24-hour urine protein excretion 13. In this patient, secretion of loop di- uretics is limited because of reduced renal blood Which of the following factors may contribute to re- flow and accumulation of organic acids in renal in- sistance to furosemide in this patient? In animals, albumin in (B) Reduced active tubular secretion of furosemide the tubular fluid binds furosemide, preventing its ac- by the proximal tubule organic acid secretory cess to the Na-K-2Cl cotransporter. After prolonged mechanism use of furosemide, hypertrophy of the distal tubule epithelial cells occurs, indicating compensatory in- creased reabsorptive capacity. Anticoagulant, Antiplatelet, and 2222 Fibrinolytic (Thrombolytic) Drugs Jeffrey S. Hemostasis involves Endothelial cells maintain a nonthrombogenic lining in the interplay of three procoagulant phases (vascular, blood vessels. This results from several phenomena, in- platelet, and coagulation) that promote blood clotting to cluding (1) the maintenance of a transmural negative prevent blood loss (Fig. The fibrinolytic system electrical charge, which is important in preventing ad- prevents propagation of clotting beyond the site of vas- hesion of circulating platelets; (2) the release of plas- cular injury and is involved in clot dissolution, or lysis minogen activators, which activate the fibrinolytic path- (Fig. This figure is a highly simplified summary; see supplemental reading for further details.

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The pathogenesis of this type of complaint is attributed to struc- tures innervated by the sinuvertebral nerve or the nerves innervating the paravertebral soft tissues and is generally a localized injury lasix 100 mg mastercard arrhythmia pronunciation. The Spine 277 Another group of patients complains of neck pain with the addition of arm involvement buy discount lasix 40mg blood pressure cuff and stethoscope. The degree of nerve root involvement can vary from a monoradiculopathy to multiple levels of involvement lasix 100 mg without prescription how quickly will blood pressure medication work. It is described as a deep aching discount lasix 100mg on line blood pressure 8040, burning, or shooting arm pain, often with associated paresthesias. The pathogenesis of radicular pain can derive from soft tissue (herniated disk), bone (spondylosis), or a combination of these two. Finally, a third group of patients complains of symptoms secondary to cervical myelopathy, which is compression of the spinal cord and usually secondary to degenerative changes. The onset of symptoms usually begins after 50 years of age, and males are more often affected. The natural history is that of initial neurologic deterioration followed by a plateau period lasting several months. The resulting clinical picture is often one of an incomplete spinal lesion with a patchy distribution of deficits. Disability varies with the number of verte- brae involved and with the degree of changes at each level. Common presenting symptoms of cervical myelopathy include numbness and paresthesias in the hands, clumsiness of the fingers, weakness (greatest in the lower extremities), and gait disturbances. Abnormalities of micturi- tion are seen in about one-third of cases and indicate more severe cord involvement. Symptoms of radiculopathy can coexist with myelopathy and confuse the clinical picture. Spinothalamic tract (pain and temperature) deficits may be seen in the upper extremities, the thorax, or the lumbar region and may be in a stocking or glove distribution. Posterior column deficits (vibration and proprioception) are more commonly seen in the feet than in the hands. Usually there is no gross sensory impairment, but a diminished sense of appreciation of light touch and pinprick. A characteristic broad-based, shuffling gait may be seen, signaling the onset of functionally significant deterioration. Physical Examination the physical examination should begin with observation of the cervical spine and upper torso unencumbered by clothing. One set can be categorized as nonspecific and found in most patients with neck pain but will not help to localize the type or level of the pathologic process. It can be secondary to pain or, structurally, to distorted bony or soft tissue elements in the cervical spine. Hyperexten- sion and excessive lateral rotation, however, usually cause pain, even in a normal individual. The second type of tender- ness is more specific and may help localize the level of the pathology. It can be localized by palpation over each intervertebral foramen and spinous process. The next goal of the physical examination is to isolate the level or levels in the cervical spine responsible for the symptomatology. The exam is also important to rule out other sources of pain, which include compression neuropathies, thoracic outlet syndrome, and chest or shoulder pathology. The major focus of the exam is directed at finding a neurologic deficit (Table 7-1). A motor deficit (most commonly weak triceps, biceps, or deltoid) or diminished deep tendon reflex is the most likely objective Table 7-1. Although less reproducible, manual tests and maneuvers that increase or decrease radicular symptoms may be helpful. In the neck compression test, the patient’s head is flexed laterally, slightly rotated toward the symptomatic side, and then compressed to elicit reproduction or aggravation of the radicular symptoms. The axial manual traction test is performed in the presence of radicular symptoms in the supine position. With 20 to 25lb axial traction, a positive test is the decrease or disappearance of radicular symptoms. All these tests are highly specific (low false-positive rate) for the diagnosis of root compression, but the sensitivity (false-negative rate) is less than 50%. Pyramidal tract weakness and atrophy are more commonly seen in the lower extremi- ties and are the most common abnormal signs. Weakness and wasting of the upper extremities and hands may also be due to combined spondylotic myelopathy and radiculopathy. A diminished or absent upper-extremity deep tendon reflex can indicate compressive radic- ulopathy superimposed on spondylotic myelopathy. Sensory deficits in spinothalamic (pain and temperature) and posterior column (vibration and proprioception) function should be documented. Usually there is no gross impairment of sensation; rather, a patchy decrease in light touch and pinprick is seen. Hyperreflexia, clonus, and positive Babinski’s signs are seen in the lower extremities. Diagnostic Studies In evaluating any pathologic process, one usually has a choice of several diagnostic tests. In other words, the core of the information derived from a thorough history and physical examination should be the basis for a diagnosis; the additional tests are obtained to confirm this clini- cal impression.

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