By D. Bengerd. William Jewell College.
A rapidly activating sub- tential slowly depolarizes during this period to initiate set (IKr) buy rumalaya forte 30pills lowest price, a slowly inactivating subset (IKs) rumalaya forte 30pills visa, and an ul- an action potential (discussed later) cheap rumalaya forte 30 pills free shipping. Automaticity Phase 3: Late Phase of Repolarization Automaticity can be deﬁned as the ability of a cell to al- Termination of phase 2 of the action potential plateau oc- ter its resting membrane potential toward the excitation curs when time-dependent order 30pills rumalaya forte with visa, voltage-dependent, and in- threshold without the inﬂuence of an external stimulus. The combination of these effects results in rapid tole (phase 4) such that the membrane potential repolarization with a return to the hyperpolarized resting reaches threshold (Figure 16. Pharmacological interventions that pacemaker cells, the background potassium leak cur- inhibit IK prolong the membrane action potential by de- rent decreases and an inward depolarizing current (I ) isf 40 gCa 20 gK 0 0 0 gNa 20 gK TP 40 4 4 60 MDP Diastolic Depolarization 0 200 400 600 800 Time (msec) FIGURE 16. The maximum diastolic poten- tial (MDP) is achieved as a result of a gradual decline in the potassium conductance (gK ). Spontaneous phase 4 or diastolic depolarization permits the cell to achieve the TP, thereby initi- ating an action potential (g transmembrane ion conductance). Stimulation of pacemaker cells within the sinoatrial node decreases the time required to achieve the TP, whereas vagal stimula- tion and the release of acetylcholine decrease the slope of diastolic depolarization. Thus, the positive and negative chronotropic actions of sympathetic and parasympathetic nerve stimula- tion can be attributed to the effects of the respective neurotransmitters on ion conductance in pacemaker cells of the sinuatrial node. In combination, this results in slow depolar- block), spontaneous depolarization within the His- ization of the myocyte. If the membrane potential de- Purkinje system may become the dominant pacemaker polarizes above the threshold for the opening of I, maintaining cardiac rhythm and cardiac output. The rate of pacemaker discharge within these spe- Myocytes within the sinoatrial node possess the cialized myocytes is inﬂuenced by the activity of both most rapid intrinsic rate of automaticity; therefore, the divisions of the autonomic nervous system. Increased sinoatrial node serves as the normal pacemaker of the sympathetic nerve activity to the heart, the release of heart. Specialized cells within the atria, atrioventricular catecholamines from the adrenal medulla, or the exoge- (A-V) node, and His-Purkinje system are capable of nous administration of adrenomimetic amines will spontaneous depolarization, albeit at a slower rate. The cause an increase in the rate of pacemaker activity more rapid rate of depolarization of the sinoatrial nodal through stimulation of -adrenoceptors on the pace- cells normally suppresses all of the other cells with the maker cells (Figure 16. The other cells will become The parasympathetic nervous system, through the pacemakers when their own intrinsic rate of depolariza- vagus nerve, inhibits the spontaneous rate of depolar- tion becomes greater than that of the sinoatrial node or ization of pacemaker cells. The release of acetylcholine when the pacemaker cells within the sinoatrial node are from cholinergic vagal ﬁbers increases potassium con- depressed. When impulses fail to conduct across the ductance (gK ) in pacemaker cells, and this enhanced A-V node to excite the ventricular myocardium (heart outward movement of K results in a more negative po- TP A. The rate of spontaneous discharge is determined by the initial slope of the membrane potential and the time required to reach the threshold potential. There is a decrease in the slope of diastolic depolarization as well as hyperpolarization of the cell. The time to reach the threshold potential is prolonged, with the net effect being a decrease in the rate of spontaneous depolarization. Refractory Period Thus, during vagal stimulation, the threshold potential Depolarized cardiac cells are transiently unresponsive of the sinoatrial node pacemaker cells is achieved more to any activation stimuli. The refractory Cardiac Conduction period is subdivided into three phases, absolute, effec- tive, and relative. The absolute refractory period is the The cardiac impulse begins in the sinoatrial node in the time from the onset of the action potential until a stim- high lateral right atrium near the junction of the supe- ulus is able to evoke a local nonconducted response. Excitation leaves During this period, the cell is completely refractory to the sinoatrial node and spreads throughout the atrium. The effective re- The myocytes (both atrial and ventricular) are long thin fractory period (ERP) begins with the onset of the ac- structures linked electrically via low-resistance pores tion potential, incorporates the absolute refractory pe- known as gap junctions. The gap junctions are hetero- riod, and ends when an excitatory stimulus is able to geneously dispersed throughout the sarcolemmal mem- generate a conducted signal. The ERP is determined as brane, although they are mainly concentrated on the the shortest interval between two stimuli of equal in- ends of the myocytes. This distribution leads to polarity tensity that results in the generation of a propagated re- of the myocyte, with end-to-end conduction occurring sponse. The relative refractory period begins with the at a more rapid rate than side-to-side (anisotropic) con- completion of the ERP and continues through the time duction. The difference in conduction velocity is up to a in which a signal may be conducted slowly, prior to ob- factor of three and may be important in supporting cer- taining normal propagation of the signal.
In one ingenious study purchase 30pills rumalaya forte fast delivery, subjects were presented with a hypnotic intervention to change the distress associated with pain rather than the perception of pain 53 itself buy 30pills rumalaya forte with amex. By administering suggestions for increased or decreased unpleasantness of the pain cheap 30 pills rumalaya forte otc, rCBF changes were shown in the anterior cingulate but not in the primary 54 association cortex cheap rumalaya forte 30pills overnight delivery. The PET studies just described outlined the neurophysiological correlates of suggestions for hypnotic analgesia and altered emotional appraisal of pain. With this in mind, we now turn to general evidence for the efficacy of hypnosis in clinical interventions, especially its usefulness in the control of pain. Hypnosis 211 THE STATUS OF HYPNOSIS AS AN EMPIRICALLY VALIDATED CLINICAL INTERVENTION Probably no contemporary therapeutic intervention has a longer history than that of hypnosis. In a recent special issue of the leading journal of hypnosis research, The International Journal of Clinical and Experimental Hypnosis, evidence for the efficacy of hypnosis in clinical treatment was critically examined following the guidelines advanced 55 by Chambless and Hollon for empirically supported therapies. The arena in which hypnosis has probably proved itself most adequately is that of hypnotically induced analgesia, providing reduction of both chronic (e. Hypnotic analgesia has a long history, with prominent figures such as the Scottish surgeon James Esdaile (1808–59) demonstrating its apparent effectiveness for surgery (including 200 patients with massive scrotal tumors) during his time in India. Beginning around 1930, interest in the reduction 57,58 59 of pain by hypnosis resumed and today, from burn wound debridement to childbirth 60 61 to bone marrow aspirations and cancer in children, hypnosis has found recognition as a dramatic method of producing analgesia which in some cases has matched or exceeded that derived from morphine. Additionally, research with naloxone, a drug that acts as a competitive antagonist at the opioid receptor, shows that hypnotic analgesia is not 62 mediated by endogenous pain mechanisms involving endorphins. A meta- analysis of studies of hypnotically suggested pain reduction, based on pain reports from 933 participants, showed that such suggestions provide substantial pain relief for 75% of 64 the population across different types of experienced pain. In one of the included studies, 65 self-hypnotic techniques were used during interventional radiological procedures, in which intravenous pain medication was self-administered by patients by means of a push- button automated delivery system. Compared to hypnosis patients, the control patients as a whole used seven times more drug units and reported significantly more maximal pain. Not only was the pain reduction evidenced by subjective reports and behavioral response, but the reduction of drug use in the hypnosis group was associated with a significantly lower incidence of oxygen desaturation and significantly fewer procedural interruptions due to cardiopulmonary instability. Other research has shown that pain typically increases over the course of percutaneous medical procedures, but remains stable for patients using 66 self-hypnosis techniques. A recent investigation found hypnotic intervention to be effective in the reduction of pain, anxiety and distress behavior in children undergoing lumbar puncture procedures, but only when heterohypnosis (therapist-administered hypnosis) was used, 61 not when children used self-hypnosis. For those interested in examining this topic further, a recent review of Complementary therapies in neurology 212 67 review articles that deal in some fashion with hypnosis and pain provides an impressive preliminary resource. Burns, 73 74 75 76,77 allergic reactions, skin temperature, blood pressure, asthma, dermatological 78–80 disorders (e. Hypnosis was used in several of the earliest studies exploring the ability of a 81,82 psychological intervention to affect immunological reactivity. However, in spite of the large amount of literature supporting the efficacy of hypnosis in treating a variety of 83 immune-related disorders, there still remains a scarcity of solid experimental evidence demonstrating that the immune system is responsive to hypnotic suggestion. Additionally, many of the studies that examine the potential for hypnosis to influence 84 immune functioning fail to control for the effects of relaxation, a technique capable of 85 modulating the immune system. However, there have been a few studies that have examined this issue more carefully, either by utilizing measures of hypnotizability as a 86 87 subject variable or by directly controlling for relaxation. Subjects in a relaxation group participated in flotation restricted environmental stimulation therapy (REST) sessions, in which they floated effortlessly in a solution of Epsom salts in a fiberglass tank. Analysis of blood samples showed significant immunomodulation for subjects given hypnotic suggestions, based on B-cell and T-cell counts, but not for subjects who received just relaxation. A study involving children also showed increases in immune functioning as a result of hypnotic suggestions, this time in an immune component found in the saliva, secretory 88 immunoglobulin A (sIgA). Investigations from our own laboratory have suggested that the physiological mechanisms involved in the sIgA increases may differ between the two tasks (acute stress and hypnosis), but the results also demonstrate that increases in sIgA following hypnotic suggestions may be short- lived. Thus, the clinical relevance of hypnotic immunomodulation will be suitably assessed only after long-term outcome studies have demonstrated its impact on health. These reports, based on case studies with individual patients, provide a first step in demonstrating the usefulness of integrating hypnotherapeutic procedures into treatment of neurological conditions. For example, with multiple sclerosis, various symptoms have been ameliorated via hypnosis, including 97,98 99 spasticity and multiple sclerosisassociated pain. Such case studies shed little light on the underlying means of improvement and, perhaps more importantly, do not control adequately for any treatment effects due to increased motivation, attention, or relaxation.
FPL has separated as a daughter muscle from the ancestral FDP buy cheap rumalaya forte 30pills line, the index ﬁnger portion of FDP has its own tendon cheap 30 pills rumalaya forte fast delivery, and the belly is partially cheap rumalaya forte 30 pills fast delivery, though incompletely generic rumalaya forte 30 pills otc, separate from the middle ﬁnger portion, while the ring and little ﬁnger portions still retain a partially inter- connected tendon. Evolutionary variations have made the muscles acting on a biological hand quite different from the independent motors and cables that operate a robotic hand. Output neurons in layer V of M1 have several features of the descending neurons in the evolutionary schema described above. Many single M1 neurons have outputs that diverge to innervate multiple spinal motoneuron pools. The fact that divergent connections remain today suggests, however, that they are important to the present function of the motor cortex. Their importance may lie in the fact, described above, that the most frequently performed behavioral tasks, such as grasp- ing, require the simultaneous contraction of multiple muscles acting on multiple ﬁngers. These movements may be controlled most efﬁciently through M1 neurons with divergent connections to multiple muscles. Because the output of many single M1 neurons diverges to multiple muscles (often muscles that move different digits and/or the wrist), different muscles receive inputs from intersecting sets of M1 neurons. The sets of M1 neurons that provide input to two muscles acting on the digits and wrist also are intermingled in the physical space of the cortex. Consequently, the neurons that provide input to any given muscle are spread over a relatively large cortical territory (typically a few millimeters in diameter in nonhuman primates) and the territory providing input to one muscle overlaps extensively with the territory providing input to other mus- cles. When ﬁnger movements are made, then, active neurons are found over a rela- tively large M1 territory, and similar territories are activated for different ﬁnger movements. Widespread activation of the M1 hand representation during individu- ated ﬁnger movements has been observed in both monkeys and humans. In monkeys, Copyright © 2005 CRC Press LLC microelectrode recording typically reveals a burst of the background “hash” (which presumably reﬂects the discharge of action potentials by numerous neurons and axons in the vicinity of the microelectrode tip) with every ﬁnger movement, no matter where within the M1 hand region the microelectrode tip is located. Single neurons likewise are observed to discharge in relation to multiple ﬁnger and wrist movements. The distribution of neurons active during movements of particular digits gives little if any evidence of somatotopic segregation of neurons controlling differ- ent digits. Similarly in humans, functional magnetic resonance imaging (fMRI) shows that a similar cortical territory is activated no matter which digit is moved. M1 lesions do not impair the function of particular muscles in isolation, but rather impair many functionally related muscles at the same time. In monkeys, injection of the gamma amino butyric acid (GABA) agonist, muscimol, at a single location in the M1 hand representation produces partial inactivation, impairing some ﬁnger movements but not others. Rather than producing selective impairment of different ﬁngers in different patients, however, such infarcts impair either the radial digits (thumb and index ﬁnger) more than the ulnar digits (little, ring, and middle ﬁngers) or vice versa. Conceivably, even if groups of functionally similar neurons were not spatially segregated in a somatotopic fashion in M1, groups of similar neurons still might control particular ﬁngers, muscles, or muscle synergies. Neurons of different distinct functional groups could be intermingled in the physical space of M1. We have used cluster analysis to search populations of M1 neurons for such groups of functionally similar neurons. In three monkeys, however, cluster analysis revealed only two consistent groups of M1 neurons. A relatively large group consisted of neurons that increased discharge during most if not all ﬁnger and wrist movements; another small group decreased discharge during most movements. These two groups were found in all three monkeys, were robust against changing the method of quantifying neuronal activity or changing the clustering algorithm, and were not reproduced when the data was randomly reshufﬂed. In contrast, small groups of neurons that discharged during particular subsets of ﬁnger and wrist movements varied from monkey to monkey, changed when the means of quantifying neuronal activity or the clustering algorithm was changed, and appeared in randomly reshufﬂed data. This analysis suggests that during individuated ﬁnger and wrist movements, M1 neurons do not work as groups of functionally similar neurons. The view of M1 activity during individuated ﬁnger movements that has devel- oped up to this point appears chaotic. Although voluntary movements of different ﬁngers obviously can be made as desired, which ﬁnger movement is performed does not appear to be determined by where in M1 neurons are active, nor by the activity of neuronal groups controlling particular muscles, muscle synergies, digits, move- ments, or movement primitives. And yet the M1 neuronal populations do transmit ﬁring rate information about which ﬁnger movement is made.
The prevalence rates range from less than one in 10 purchase rumalaya forte 30 pills overnight delivery,000 IAnencephaly births (European countries) to more than 10 per 10 rumalaya forte 30 pills on-line,000 Definition births (Mexico order rumalaya forte 30pills with mastercard, China) discount 30 pills rumalaya forte overnight delivery. Anencephaly is a lethal birth defect characterized by the absence of all or part of the skull and scalp and mal- Signs and symptoms formation of the brain. Anencephaly is readily apparent at birth because of exposure of all or part of the brain. Not only is the brain Description malformed, but it is also damaged because of the Anencephaly is one of a group of malformations of absence of the overlying protective encasement. In about the central nervous system collectively called neural 10% of cases of anencephaly, other malformations are tube defects. The condition is also Diagnosis called acrania (absence of the skull) and acephaly (absence of the head). In most instances, anencephaly nosis of anencephaly can also be detected through occurs as an isolated birth defect with the other organs maternal serum alpha-fetoprotein screening. In approxi- of alpha-fetoprotein in the maternal blood is elevated mately 10% of cases, other malformations coexist with because of the leakage of this fetal protein into the anencephaly. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 89 Diagram of Anencephaly NORMAL INFANT ANENCEPHALIC INFANT Brain Brain Stem Brain Stem Infants born with anencephaly have either a severly underdeveloped brain or total brain absence. A portion of the brain stem usually protrudes through the skull, which also fails to develop properly. Affected infants are stillborn or die within the first few ORGANIZATIONS days of life. Stevenson, MD all enriched cereal grain flours have been fortified with folic acid. Prognosis Anencephaly is uniformly fatal at birth or soon IAngelman syndrome thereafter. Definition Resources Angelman syndrome (AS) is a genetic condition that PERIODICALS causes severe mental retardation, severe speech impair- Czeizel, A. Individuals with AS show evidence of delayed “Prevention of neural tube defects: results of the Medical development by 6–12 months of age. However, receptive language skills (listen- designated 15q11-13 (bands 11 through 13 on the long ing to and understanding the speech of others) and non- arm of chromosome 15). Imprinting is a chemical gait ataxia (a slow, unbalanced way of walking) and modification of DNA which acts as an “identification tag” tremulous movements of the limbs. Imprinted genes or chromosome regions are expressed or AS is also associated with a unique “happy” behav- not expressed depending on which parent transmitted the ior, which may be the best-known feature of the condi- chromosome. This may include frequent laughter or smiling, often 15q11-13 region (from the father) cause a different with no apparent stimulus. These characteristic behaviors led to the origi- nal name of this condition, the “Happy Puppet” The most common cause of AS is a small deletion syndrome. However, this name is no longer used as it (missing piece) in the maternally inherited chromosome is considered insensitive to AS individuals and their 15. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 91 UBE3A mutation Signs and symptoms In approximately 11% of AS cases, there is a muta- The first abnormalities noted in an infant with AS are tion within the maternally inherited UBE3A gene. All often delays in motor milestones (those related to physi- the genetic mechanisms leading to AS appear to compro- cal skills, such as sitting up or walking), muscular hypo- mise expression of this gene, which is located within the tonia (poor muscle tone), and speech impairment. This gene is considered to be the “crit- infants seem unaccountably happy and may exhibit fits of ical gene” responsible for AS, although its specific func- laughter. Uniparental disomy Seizures occur in 80% of children with AS, usually by three years of age. No major brain lesions are typi- Some cases of AS result from inheritance of both cally seen on cranial imaging studies. Additionally, children may have drooling, protrusion of the tongue, hyperactivity, Imprinting defect and a short attention span. Approximately 3% of AS cases result from an Many children have a decreased need for sleep and imprinting defect on the maternally inherited chromo- abnormal sleep/wake cycles. As noted above, imprinting is a chemical mod- in infancy and persist throughout childhood. Upon awak- ification to the DNA which serves as a marker indicating ening at night, children may become very active and the parent of origin and controls gene expression.