By M. Gonzales. American Institute for Computer Sciences.

The authors interpreted the oscillatory bursts as markers of the succession of dynamic stages in the production of movement buy serpina 60 caps without a prescription. Some leads showing this activity were in the rolandic area cheap serpina 60caps without prescription, or over the cingulate motor area order serpina 60 caps free shipping. The theta rhythm was obviously not driving movement purchase serpina 60caps online, but it could have been influencing a premotor network involved in setting up the motor performance. Because the theta rhythm was phase-locked to EMG onset, there is a possibility that it was used as a temporal reference for preparatory activity, analogous to the use of theta rhythm in hippocampus for coding spatial position. The theta activity was much more prominent during virtual movement on the videoscreen than while “standing still. Andersen and Eccles postulated that groups of thalamocortical neurons were synchronized into a common rhythm by mutual axon collateral inhibition (via the reticular nucleus) and postinhibitory rebound. Today more emphasis is placed on the complementary oscil- latory mechanisms within the cortex itself, but both thalamus and cortex are important. Jasper and Stefanis25 showed that one to two shocks of intralaminar thalamus were sufficient to elicit a spindle of “recruit- ing responses,” at about 10 Hz, in cat motor cortex (Figure 7. The surface negative peak of the spindle oscillation corresponded with a wave of depolarization and spiking in pyramidal tract neurons. They suggested that the rhythm of oscillatory waves was determined by inhibitory phasing of alternating excitatory and inhibitory postsynaptic potentials (PSPs), facilitated by postinhibitory rebound hyperexcitabil- ity. Since antidromic activation of PT cells also could elicit the oscillation (although not quite as well as thalamic stimulation), recurrent collaterals of pyramidal cells probably contributed to the rhythmogenic feedback loop. Above all, synchronization of a population of neurons into a common oscillatory cycle is accomplished by intracellular PT cell + 30 mV − 1 mV layer 1 LFP stim 1 sec FIGURE 7. A double shock stimulus to the intralaminar thalamus, marked by two solid circles, triggers a subsequent spindle oscillation in the cat motor cortex. Simultaneous recordings were made of the mem- brane potential of a PT cell, and of the LFP in overlying cortical layer 1. Note that the PT cell is regularly depolarized in synchrony with the negative peak of each LFP cycle, and occasionally discharges. A critical mass of synchronous discharge is recruited via gap junctions linking large numbers of inhibitory interneurons (not shown). Simultaneous LFP in deep layers of area 4, intracellular potential of an unidentified cortical neuron, and histogram of extracellular spikes from a thalamic reticular neuron. Since the earliest effect following the stimulus was a suppression of firing, inhibitory feedback was a key mechanism, as always. The same stimulus also reset ongoing beta rhythm (20 Hz), suggesting a close relationship in the circuitry underlying both oscillatory frequencies. These effects were expressed only during a static motor episode, namely a maintained precision grip. Intrinsic membrane properties of both thalamic and neocortical neurons allow them to oscillate within different frequency spectra, usually in the range of 1–20 Hz. The reticular thalamic neurons oscillate even more readily than thalamic neurons them- selves. Both the thalamic neurons give collaterals to the reticular thalamic nucleus on their way to the cortex, and the cortical pyramidal cells also give collaterals as they return to the thalamus. So the entire circuit includes recurrent inhibitory loops within both the thalamus and cortex, reinforcing intrinsi- cally oscillatory membrane potentials, plus coupling of the thalamus and cortex such that they synchronize in the same rhythm. Modeling reveals that thalamic rhythmicity depends on cortical excitatory input being stronger to reticular thalamic neurons (which are themselves inhibitory) than to thalamocortical projection cells. The thalamocortical circuit initially entrains a small cortical focus, and corticocortical connections dis- tribute the synchronization up to 4 mm in different directions. It had alternating sharp positive peaks and rounded negative waves, as shown in Figure 7. From the start, Gastaut recognized that the mu rhythm was closely allied with beta rhythm; he considered mu an amplified form of beta at half the frequency.

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With age generic serpina 60 caps fast delivery, muscles and and larger spaces appear between sections of tissue discount 60 caps serpina overnight delivery, especially in other tissues waste from loss of cells generic serpina 60caps free shipping, a process termed at- the frontal lobe generic 60 caps serpina with mastercard. Others—immunotherapy, hormones, inhibitors of hoarseness or cough, change in mole, lump, nonhealing blood vessel formation sore, pain, weight loss Questions for Study and Review Building Understanding Fill in the blanks 1. Examples of diseases caused by infectious organisms are colds, AIDS, “strep” Other factors that enter into the production of a disease throat, tuberculosis, and food poisoning. Although a predis- may also contribute to more complex disorders, for exam- posing cause may not in itself give rise to a disease, it in- ple, stomach ulcers and some forms of heart disease. Most of us are familiar with dis- early heart disease, whereas women are more likely to eases caused by a dietary lack of essential vitamins, develop adult onset diabetes and autoimmune diseases. Some individuals inherit a “tendency” to ac- health: scurvy due to a lack of vitamin C; beriberi due quire certain diseases—particularly diabetes, many al- to a lack of thiamine; rickets due to a lack of calcium for lergies, and certain forms of cancer. Some physical disturbances have reactions involved in cellular metabolism, such as dia- their basis in emotional upsets, stress, and anxiety in daily betes, gout (a disorder of the joints), digestive disorders, living. Injuries that cause and the diseases caused by excess or deficiency of hor- burns, cuts, fractures, or crushing damage to tissues mones are the subject of Chapter 12. Metals DISEASE AND DISEASE-PRODUCING ORGANISMS ✦ 79 or toxins may cause skin reactions, and exposure to pes- tions, public health workers use the term morbidity rate to ticides and other agricultural chemicals has been associ- describe the proportion of people with a specific disease in a ated with neurologic disorders and cancer. Any preexisting illness, especially a scribe the percentage of the population that dies from a chronic disease such as high blood pressure or diabetes, given disease within a period of time. Epidemics of influenza, for example, occur periodically today, and epidemics of The study of the cause of any disease, or the theory of its ori- smallpox and bubonic plague occurred in earlier ages. Any study of a disease usually includes some indication of incidence, which means its a given disease is found to a lesser extent but continu- range of occurrence and its tendency to affect certain groups ously in a particular region, the disease is endemic to that of individuals more than other groups. A disease that is prevalent throughout an entire appear in one gender, age group, or race more or less fre- country or continent, or the whole world, is said to be quently than another is usually included in any study on dis- pandemic. Box 5-1 A Closer Look The CDC: Making People Safer and HealthierThe CDC: Making People Safer and Healthier he Centers for Disease Control and Prevention (CDC) in polio, which has virtually been eliminated in the United States. TAtlanta, Georgia, are responsible for protecting and im- In the 1960s the CDC joined the World Health Organization in proving the health of the American public—at home and efforts to eradicate smallpox worldwide, and in the 1970s, it abroad. During the 1990s, CDC researchers rapidly identified works to protect the public from environmental hazards such the strain of hantavirus that caused a serious and often fatal as waterborne illnesses, weather emergencies, biologic and pulmonary disease in people in the Southwestern U. National Institutes of Health (NIH) has es- To treat a patient, a physician must first make a diagnosis tablished the National Center for Complementary and Al- (di-ag-NO-sis), that is, reach a conclusion as to the nature ternative Medicine (NCCAM) to study the value of these of the illness. A characteristic typically they are measured, purified, and often modified group of symptoms and signs that accompanies a disease is instead of being used in their natural state. Some complex disorders purity, safety, dosage, and effectiveness have arisen in the even have “syndrome” in their names, such as Down syn- use of herbal remedies as, to date, they have not been drome, premenstrual syndrome, acquired immunodefi- tested as rigorously as conventional drugs. Common methods used for diagnosis however, restrictions on the health claims that can be include imaging studies, blood tests, and study of tissues re- made by the manufacturers, and the Federal Drug Admin- moved in biopsy. Nurses and other healthcare professionals play an ex- tremely valuable role in the diagnostic process by observ- Prevention of Disease ing closely for signs, collecting and organizing informa- In recent years, physicians, nurses, and other healthcare tion from the patient about his or her symptoms, and then workers have taken on increasing responsibilities in pre- reporting this information to the physician. The modern concept of prevention, however, include drugs, surgery, radiation, counseling, physical or seeks to stop disease before it actually happens—to keep occupational therapy, and many others, alone or in com- people well through the promotion of health. Specific measures in a course of treatment in- provement include cessation of smoking, improved diet, clude those carried out by the nurse and other healthcare weight control, and adequate exercise. An insect or other animal that transmits a mans, and many are beneficial, a few types cause illness; disease-causing organism from one host to another is that is, they are pathogenic (path-o-JEN-ic). For example, people with depressed ample, discharges from the respiratory and intestinal tracts immune systems, such as those with AIDS become infected may spread infection through air, by contamination of hands, with organisms that are ordinarily harmless. In close quarters, germ-laden droplets discharged by Box 5-2 • Health Maintenance The Cold Facts about the Common ColdThe Cold Facts about the Common Cold very year, an estimated one billion Americans suffer from temperature and humidity, these particles may live as long as Ethe symptoms of the common cold—runny nose, sneez- 3 to 6 hours, and others who touch the contaminated surface ing, coughing, and headache. Although the term parasitology (par-ah-si-TOL-o-je) is the study Microorganisms of parasites in general, in practice, it usually refers to Microorganisms are simple, usually single-cell forms of the study of protozoa and worms (helminths). The organisms included These organisms rarely cause diseases and will not be de- in the study of microbiology along with their scientific scribed any further in this chapter. Others produce the fer- Table 5•1 Organisms Studied in Microbiology TYPE OF NAME OF CHARACTERISTICS OF REPRESENTATIVE ORGANISM STUDY ORGANISMS EXAMPLES Bacteria Bacteriology Simple, single-cell organisms.

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The cipitate seizures in some patients 60 caps serpina visa, particularly those ex- plasma half-life after a single dose is about 24 hours buy generic serpina 60 caps. Unlike most drugs discount 60caps serpina amex, lamotrigine is metabolized primarily While the number of side effects may be fairly large cheap serpina 60 caps, by glucuronidation. Severe ad- lamotrigine will not induce or inhibit cytochrome P450 verse reactions occur less commonly than with pheny- isozymes, in contrast to most AEDs. The overall incidence of toxicity Severe skin rashes appear to be the major concern seems to be fairly low at usual therapeutic doses. The incidence of rash is greater in Most of the drug interactions with carbamazepine children than in adults. Other adverse effects are similar are related to its effects on microsomal drug metabo- to those of drugs with the same mechanism of action, lism. Carbamazepine can induce its own metabolism such as cerebellovestibular changes leading to dizziness, (autoinduction) after prolonged administration, de- diplopia, ataxia, and blurred vision. Disseminated in- creasing its clearance rate, half-life, and serum concen- travascular coagulation has been reported. Topiramate is most useful in patients with generalized Carbamazepine also can induce the enzymes that tonic–clonic seizures and those with partial complex metabolize other anticonvulsant drugs, including seizures. Topiramate causes a higher incidence of CNS- phenytoin, primidone, phenobarbital, valproic acid, related side effects (primarily cognitive slowing and clonazepam, and ethosuximide, and metabolism of confusion) than other AEDs. Similarly, other cause a significant incidence of rashes or other hyper- drugs may induce metabolism of carbamazepine; the sensitivity reactions; however, a significantly higher in- end result is the same as for autoinduction, and the dose cidence of kidney stones has been observed in persons of carbamazepine must be readjusted. A common receiving topiramate than in a similar untreated popu- drug–drug interaction is between carbamazepine and lation. After a few days of antibiotic therapy, symp- Zonisamide toms of carbamazepine toxicity develop; this is readily Zonisamide has only recently been approved for use in reversible if either the antibiotic or carbamazepine is the United States, although it has been available in discontinued. It is effective in partial complex Cimetidine, propoxyphene, and isoniazid also have and generalized tonic–clonic seizures and also appears been reported to inhibit metabolism of carbamazepine. It has a It is essential to monitor blood levels and adjust the long half-life (about 60 hours) and requires about 2 dose if necessary whenever additional drugs are given weeks to achieve steady-state levels. In addi- Oxcarbazepine tion, it appears to cause an increased incidence of kid- Oxcarbazepine is chemically and pharmacologically ney stones. This Valproic Acid (Sodium Valproate) property decreases the problems associated with drug Although it is marketed as both valproic acid interactions when oxcarbazepine is used in combination (Depakene) and as sodium valproate (Depakote), it is with other drugs. The clinical uses and adverse effect the valproate ion that is absorbed from the gastroin- profile of oxcarbazepine appear to be similar to those of testinal tract and is the active form. This com- Lamotrigine pound has broad anticonvulsant activity, both in exper- Lamotrigine has a broad spectrum of action and is ef- imental studies and in the therapeutic management of fective in generalized and partial epilepsies. Valproic acid has been shown to block mechanism of action appears to be blockage of voltage- voltage-dependent sodium channels at therapeutically dependent sodium channels, although its effectiveness relevant concentrations. In several experimental stud- against absence seizures indicates that additional mech- ies, valproate caused an increase in brain GABA; the anisms may be active. There is evidence that valproate 380 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM may also inhibit T-calcium channels and that this may Drugs That Primarily Enhance the Action be important in its mechanism of action in patients with of GABA absence epilepsy. A major effort has been directed to the search for Valproic acid is well absorbed from the gastroin- agents that can mimic, facilitate, prolong, or enhance the testinal tract and is highly bound (~90%) to plasma pro- actions of GABA, with the expectation that such com- tein, and most of the compound is therefore retained pounds will likely be beneficial in the treatment of con- within the vascular compartment. Although there have been some dis- ters the brain from the circulation; the subsequent de- appointments, in general this appears to be a fruitful cline in brain concentration parallels that in plasma, in- approach in the search for better and safer antiepileptic dicating equilibration between brain and capillary compounds. A large number of metabolites have been identi- fied, but it is not known whether they play a role in the Benzodiazepines anticonvulsant effect of the parent drug. Valproic acid inhibits the metabolism of several drugs, including phe- Several benzodiazepines are used in the management of nobarbital, primidone, carbamazepine, and phenytoin, epileptic seizures, although only a few are approved for leading to an increased blood level of these compounds. At high doses, valproic acid can inhibit its own metabo- Since the benzodiazepines share many properties, they lism. It can also displace phenytoin from binding sites will be discussed as a class; individual members will be on plasma proteins, with a resultant increase in un- mentioned for specific indications. In The primary action of the benzodiazepines as anti- this instance, the dosage of phenytoin should be ad- convulsants is to enhance inhibition through their inter- justed as required.

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Conversely cheap 60 caps serpina otc, the participation of primary visual cortex in mental imagery has been far more difficult to demonstrate and does not reach the strength of effects that visual imagery evokes in higher-order areas purchase 60caps serpina with visa. Nonetheless order 60 caps serpina fast delivery, there is now a consensus that the primary visual cortex can participate in imagery serpina 60caps amex, and this may depend on Copyright © 2005 CRC Press LLC specific aspects of the paradigm employed, such as the requirement of processing capacities that are best represented at this cortical level. If we attempt to transfer this analogy to the sensorimotor system we must analyze in greater depth the paradigms employed across the various motor imagery studies. Indeed, it seems to be the case that only studies employing the latter strategy have reported robust effects in M1. This means that the fMRI responses would then be accounted for, not necessarily by the executive neural elements in M1, but by those dealing with proprioceptive input in the context of movement. Psychophysically, it was found that motor imagery affects the illusory perception of movement created by a purely proprioceptive stimulus. It should be noted that this experiment was carried out using PET, and it may therefore have suffered from sensitivity or spatial resolution limitations. At the same time, the authors reproduced their finding of M1 activation from the illusion, and it hence seems unlikely that this should be accounted for by the movement illusion rather than by proprioceptive processing. However, the initial PET investigations characterized neural correlates of response preparation by comparing conditions either involving or not involving motor preparation,130–133 rather than by following the electrophysiological approach of isolating specific delay-related neural activity. First, it is possible to isolate preparatory activity by directly comparing trials with and without a preparatory component, other factors being equal. In other words, one needs to assume that movement preparation is a stand- alone cognitive module, indifferent to the selection and execution components of the sensorimotor process. But response selection appears to be significantly influ- enced by the possibility of preparing a response before a trigger cue. In the context of motor preparation, it is possible to overcome this limitation by isolating specific delay-related activity, while accounting for selection and execution components of the sensorimotor process. Although it might be important to define which regions are impli- cated in movement preparation, neuroimaging studies have usually avoided address- ing the crucial question of how a given cerebral region contributes to the preparatory process. A few notable exceptions to this consideration come from fMRI studies trying to investigate the dynamics of the BOLD signal to gather temporal information from the pattern of hemodynamic responses evoked by a given motor task. The rationale behind this approach is to extract the sequence of neural events occurring during a given motor task in order to map different cerebral regions onto different stages of a given cognitive process. Their results showed consistent temporal precedence of the onset of the BOLD response in a mesial ROI (putative SMA) as compared to a lateral ROI (putative M1). However, these data do not allow one to infer that the temporal offset is neural in nature. It might equally well be the case that mesial and lateral regions have different neurovascular coupling properties. The authors found a temporal shift of the BOLD response between the rostral portion of SMA and M1 of 2000 msec during the self- generated movements compared to only 700 msec during the externally triggered movements. By correlating the dif- ference in fMRI response onset of pairs of regions (visual cortex–supplementary motor area; supplementary motor area–primary motor cortex) with the reaction times on a subject-by-subject basis, the authors showed that reaction time differences could be predicted by BOLD delays between SMA and M1, but not between V1 and SMA. In other words, the authors localized the source of visuomotor processing delays to the motor portion of the sensorimotor chain bringing visual information to the motor cortex. However, one could argue that the observations of these reports143,144 crucially depend on how BOLD delays are measured. In both studies, the authors fitted a linear regression to the initial uprising portion of the BOLD response. The intercept Copyright © 2005 CRC Press LLC of this regressed line with “zero intensity” was taken as the onset point of the BOLD response. Therefore, this measure of response onset depends crucially on defining a stable baseline. For primary sensory or motor regions it is conceivable to define baseline as the absence of sensory stimuli or motor responses, but this criterion would not be appropriate for higher order cerebral regions. There is a further difficulty with this approach, namely, how to disentangle changes in response mag- nitude from changes in response latency. To summarize, the studies on the contribution of M1 to movement preparation reviewed here agree in suggesting that this cortical region is mainly involved in the executive stages of the sensorimotor chain. This role seems to fit into the more general perspective of the organization of the parieto-frontal system, with parietal areas involved in evaluating the potential motor significance of sensory stimuli,141,149 frontal areas involved in preparing movements as a function of their probability,150,151 and central regions focused on executing the actual movement.

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