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The prefrontal cortex plays an especially important role in the acquisition and im- plementation of task rules buy ranitidine 150 mg mastercard gastritis patient handout. For example purchase ranitidine 300mg line gastritis water, in rats performing an odor-guided version of the DNMS task, damage to the orbitofrontal cortex resulted in a deficit in the ac- quisition of the task when the memory delay was minimal, suggesting an important role in perceptual processing or in learning the nonmatching rule (Otto and Eichen- baum, 1992; Ramus and Eichenbaum, 2000). The prefrontal cortex is parcellated into several distinct areas that have di¤erent inputs and whose functions can be dissoci- ated according to di¤erent modalities of stimulus processing. However, they share common higher-order functions in working memory and strategic processing, which is reflected in perseveration and other common strategic disorders following damage to any of the subdivisions (Eichenbaum and Cohen, 2001; Miller, 2000; Fuster, 1995; Goldman-Rakic, 1996). In contrast to the e¤ects of prefrontal damage, rats with damage to the parahippocampal region acquired the DNMS task at the normal rate and performed well at brief memory delays. How- ever, their memories declined abnormally rapidly when the memory delay was ex- tended beyond a few seconds, indicating a selective role in maintaining a persistent memory of the sample stimulus (see also Young et al. Little if any deficit in nonspatial DNMS is observed following damage to the hippocampus or its connec- tions via the fornix, indicating that the parahippocampal region itself mediates the persistence of memories for single items needed to perform the DNMS task. A Protocol for Reading the Mind 95 Parallel results have been obtained in monkeys performing visually guided versions of the DNMS task. Similar to rats, monkeys with damage to the parahippocampal region perform well when the memory delay is brief. However, when the memory demand is increased by extending the delay period, severe deficits in DNMS are observed (Meunier et al. The parahippo- campal region may also play a role in the intersection of perception and memory, in situations where perceptual processes depend on learned associations among com- plex stimulus elements (Eichenbaum and Bunsey, 1995; Murray and Bussey, 1999). The Role of the Hippocampus Itself It is notable that memory mediated by the hippocampus itself contributes very little to performance in standard DNMS tasks, in that the deficits observed are modest at most compared with the e¤ects of damage to the cortex or parahippocampal region. However, the hippocampus may play an essential role in other types of simple recog- nition memory tests (Zola et al. Instead, the findings from studies using animal models point to a critical role for the hippocampus itself in central aspects of declarative memory. To understand this role, it is important to consider the fundamental properties of declarative memory, as introduced by Cohen and Squire (1980) and subsequently elaborated by many investigators. But the full scope of hippocampal involvement also extends to semantic memory, the body of general knowledge about the world that is accrued by linking multiple experiences that share some of the same information (Squire and Zola, 1998). For example, we learned about our relatives via personal episodes of meeting and talking about family members, and then weaving this information into a body of knowledge constituting our family tree. Similarly, we learned about the geographies of our neighborhood and home town by taking trips through various areas and eventually interconnecting the information in cognitive maps. In addition, declarative memory for both episodic and semantic information is special in that the contents of these memories are accessible through various routes. Most commonly in humans, declarative memory is expressed through conscious, e¤ortful recollection. This means that one can access and express declarative memo- ries to solve novel problems by making inferences from memory. Thus, even without ever explicitly studying your family tree and its history, you can infer indirect 96 Howard Eichenbaum A. In the sample phase, the subject was pre- sented with a cup containing a scented mixture of sand and ground rat chow with a buried reward. Both choice items involved odors that were di¤erent from the sample odor, and which item was baited depended on the identity of the sample. Left: Rats are first trained on two overlapping sets of paired associates. Letters represent odor stimulus items; arrows indicate the correct A Protocol for Reading the Mind 97 relationships, or the sequence of central events in the family history, from the set of episodic memories about your family. Similarly, without ever studying the map of your neighborhood, you can make navigational inferences from the synthesis of many episodic memories of previous routes taken. Within this view, a broad range of such networks can be created, with their central organizing principle the linkage of epi- sodic memories by their common events and places, and a consequent capacity to move among related memories within the network. These properties of declarative memory depend on the functions of the hippocam- pus itself. Several experiments have shown that the hippocampus is required in situa- tions where multiple and distinct, but overlapping experiences must be combined into a larger representation that mediates expression of flexible, inferential memory. For example, in one experiment, rats initially learned a series of distinct but overlapping associations between odor stimuli (Bunsey and Eichenbaum, 1996; figure 5.

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Drugs that increase effects of indomethacin: (1) Anticoagulants ranitidine 300mg sale gastritis kronis, oral Increase risk of gastrointestinal bleeding generic 300mg ranitidine visa gastritis diet . Indomethacin causes gastric irritation and is considered an ulcerogenic drug. Drugs that decrease effects of indomethacin: (1) Antacids Delay absorption from the gastrointestinal tract h. Drugs that decrease effects of allopurinol, probenecid, and sulfinpyrazone: (1) Alkalinizing agents (eg, sodium bicarbonate) Decrease risks of renal calculi from precipitation of uric acid crys- tals. Alkalinizing agents are recommended until serum uric acid levels return to normal. Recommended for concurrent use until serum uric acid levels return to normal. Drugs that increase effects of ergot preparations: (1) Vasoconstrictors (eg, ephedrine, epinephrine, phenyl- Additive vasoconstriction with risks of severe, persistent hyper- ephrine) tension and intracranial hemorrhage j. Drugs that increase the effects of triptan antimigraine drugs: (1) Monoamine oxidase inhibitors (MAOIs) Increase serum levels of triptans and may cause serious adverse effects, including cardiac arrhythmias and myocardial infarction. Triptans and MAOIs must not be taken concurrently; a trip- tan should not be taken for at least 2 weeks after an MAOI is discontinued. How do aspirin and other NSAIDs produce analgesic, Answer: The symptoms may be related to her medications, but antipyretic, anti-inflammatory, and antiplatelet effects? What adverse effects occur with aspirin and other inflammatory drugs) is gastric irritation that can cause gastro- NSAIDs, especially with daily ingestion? Compare and contrast the uses and effects of aspirin, so patients get used to the fatigue. Refer her to her physician, who will test her stool for acetaminophen be preferred? For a 50-year-old adult with rheumatoid arthritis, would Most important, to prevent falls and accidental injury, make sure aspirin, another NSAID, or acetaminophen be preferred? CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 123 6. For a 75-year-old adult with osteoarthritis and a long his- Drug facts and comparisons. Louis: Facts and tory of stomach trouble, would aspirin, another NSAID, Comparisons. Worsening of hypertension by NSAIDs, and acetaminophen, what information must be cyclooxygenase-2 inhibitors. What is the rationale for using acetylcysteine in the treat- controlled trial of glucosamine to control pain in osteoarthritis of the knee. What is the rationale for combining opioid and non- Philadelphia, Abstract No. If you were a client, what information do you think would Philadelphia: Lippincott Williams & Wilkins. CLIENT TEACHING GUIDELINES Antianxiety and Sedative-Hypnotic Drugs General Considerations dient in OTC sleep aids (eg, Compoz, Nytol, Sominex, Uni- ✔ Nerve pills and sleeping pills can relieve symptoms som) and many pain reliever products with PM as part of temporarily but they do not cure or solve the underlying their names (eg, Tylenol PM). With rare exceptions, these drugs are recom- press brain functioning when taken alone, combining them mended only for short-term use. For long-term relief, produces additive depression and may lead to excessive counseling or psychotherapy may be more beneficial be- drowsiness, difficulty breathing, traumatic injuries, and cause it can help you learn other ways to decrease your other potentially serious adverse drug effects. Physical exercise, reading, craft ingestion may lead to serious adverse effects. Also, do not work, stress management, and relaxation techniques keep the drug container at the bedside, because a person sedated by a previous dose may take additional doses. These mind- ✔ Try to identify and avoid factors that cause nervousness or altering, brain-depressant drugs should be taken only by insomnia, such as caffeine-containing beverages and stim- those people for whom they are prescribed. This may prevent or decrease the severity of ✔ Do not stop taking a Valium-related drug abruptly. With- nervousness or insomnia so that sedative-type drugs are drawal symptoms can occur. These drugs lose ✔ Most nerve pills and sleeping pills belong to the their effectiveness in 2–4 weeks if taken nightly, and same chemical group and have similar effects, including cause sleep disturbances when stopped. Thus, there is no logical reason (Zantac), a drug for heartburn and peptic ulcers. Ati- Self-Administration van, Xanax, Valium, and Restoril are commonly used ex- ✔ Follow instructions carefully about how much, how often, amples of this group, but there are several others as well.

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Thus ranitidine 150mg cheap prepyloric gastritis definition, edema may occur acids are reabsorbed; about 80% of water cheap ranitidine 150mg amex gastritis diet , sodium, potas- with burns and trauma or allergic and inflammatory sium, chloride, and most other substances is reabsorbed. In the descending limb of the loop of Henle, water from a sequence of events in which increased is reabsorbed; in the ascending limb, sodium is reabsorbed. This is the primary mechanism for marily by the exchange of sodium ions for potassium ions edema formation in heart failure, pulmonary edema, secreted by epithelial cells of tubular walls. The remaining water and solutes are now appropri- with decreased synthesis of plasma proteins (caused ately called urine. This conserves water important in keeping fluids within the blood- needed by the body and produces more concentrated urine. When plasma proteins are lacking, fluid Aldosterone, a hormone from the adrenal cortex, promotes seeps through the capillaries and accumulates in sodium–potassium exchange mainly in the distal tubule and tissues. If severe, edema Tubular Secretion may distort body features, impair movement, and inter- fere with activities of daily living. Specific manifestations of edema are determined by movement of substances from blood in the peritubular cap- its location and extent. A common type of localized illaries to glomerular filtrate flowing through the renal edema occurs in the feet and ankles (dependent tubules. Secretion occurs in the proximal and distal tubules, edema), especially with prolonged sitting or standing. In the proxi- A less common but more severe type of localized mal tubule, uric acid, creatinine, hydrogen ions, and am- edema is pulmonary edema, a life-threatening condi- monia are secreted; in the distal tubule, potassium ions, tion that occurs with circulatory overload (eg, of in- hydrogen ions, and ammonia are secreted. Secretion of travenous [IV] fluids or blood transfusions) or acute hydrogen ions is important in maintaining acid–base balance heart failure. ALTERATIONS IN RENAL FUNCTION DIURETIC DRUGS Many clinical conditions alter renal function. In some condi- tions, excessive amounts of substances (eg, sodium and water) Diuretic drugs act on the kidneys to decrease reabsorption of are retained; in others, needed substances (eg, potassium, pro- sodium, chloride, water, and other substances. These conditions include cardiovascu- classes are the thiazides and related diuretics, loop diuretics, lar, renal, hepatic, and other disorders that may be managed and potassium-sparing diuretics, which act at different sites with diuretic drugs. Major clinical indications for diuretics are edema, heart Edema failure, and hypertension. In edematous states, diuretics mo- bilize tissue fluids by decreasing plasma volume. Additional characteristics include the usually attributed to sodium depletion. Initially, diuretics following: decrease blood volume and cardiac output. Edema formation results from one or more of the fol- use, cardiac output returns to normal, but there is a persis- lowing mechanisms that allow fluid to leave the blood- tent decrease in plasma volume and peripheral vascular re- stream (intravascular compartment) and enter interstitial sistance. Diuretics Loop diuretics act at different sites in the nephron to decrease reabsorption Loop of Henle of sodium and water and increase urine output. The use of diuretic agents in the management of heart Thiazides and related drugs are contraindicated in clients failure and hypertension is discussed further in Chapters 51 allergic to sulfonamide drugs. Thiazide and Related Diuretics Thiazide diuretics are synthetic drugs that are chemically re- Loop Diuretics lated to the sulfonamides and differ mainly in their duration of action. Hydrochlorothiazide is the most commonly used; Loop diuretics inhibit sodium and chloride reabsorption in chlorothiazide is the only one that can be given IV. Related the ascending limb of the loop of Henle, where reabsorption diuretics are nonthiazides whose pharmacologic actions are of most filtered sodium occurs. Thus, these potent drugs essentially the same as those of the thiazides; they include produce significant diuresis, with their sodium-losing effect chlorthalidone, metolazone, and quinethazone. Dosage Thiazides and related diuretics are frequently prescribed can be titrated upward as needed to produce greater diuretic in the long-term management of heart failure and hyperten- effects. They act to decrease reabsorption of sodium, water, versatile diuretics available for clinical use. After oral ad- Most sodium is reabsorbed before it reaches the distal con- ministration, diuretic effects occur within 30 to 60 minutes, voluted tubule and only a small amount is reabsorbed at this peak in 1 to 2 hours, and last 6 to 8 hours. In addition, tration, diuretic effects occur within 5 minutes, peak within they are ineffective when immediate diuresis is required (be- 30 minutes, and last about 2 hours. Thus, the drugs produce cause of their slow onset of action) and relatively ineffective extensive diuresis for short periods, after which the kidney with decreased renal function. They work efficiently only tubules regain their ability to reabsorb sodium.

Seg- stimulation of group I afferents from flexor muscles mental reflexes and ankle joint muscle stiffness during co- on heterosynaptic facilitation of monosynaptic reflexes contraction of antagonistic muscles in man purchase ranitidine 300 mg visa gastritis translation. Experimental produced by Ia and descending inputs: a test for Brain Research buy ranitidine 150mg amex gastritis rice, 102, 350–8. Conditioning effect in single human motoneurones: a new Pierrot-Deseilligny, E. Evidence favouring presynaptic inhi- dependent hyperpolarisation of human motor axons bition of Ia fibres due to the activation of group III tendon produced by natural activity. Contribution of presynaptic inhibition of the soleus H reflex is temporarily peripheral afferents to the activation of the soleus muscle reduced by cortical stimulation in human subjects. Vibration-induced changes in EMG during human maneuver with segmental presynaptic inhibition. Pre- of muscle spindle discharge on the human H reflex and synaptic inhibition, EPSP amplitude, and motor-unit type the monosynaptic reflex in the cat. Cutaneous afferents are responsible for a wide range of sensations, but most are also capable of modula- Withdrawal responses ting motor behaviour through spinal, supraspinal Theseresponseshaveaspinalpathwayandarecom- and transcortical pathways. There is a tendency for monly but erroneously thought to involve a flexor clinicians to group all cutaneous afferents together, synergy activated by a nociceptive stimulus. With- and this creates confusion, leads to the usage of dif- drawal reflexes have a specific organisation, are rea- ferent terms for the same function and the same sonablystereotyped,andareelicitedbyconvergence term for different functions, and makes the systems of noxious and tactile stimuli (cf. A thesis of this flexion reflex, the corresponding pathways were book, addressed in many chapters, is that cutaneous named FRA (flexor reflex afferent) pathways. The nociceptive withdrawal vant pathways is inhibited by activation of pathways (flexion) reflex was subsequently shown to be poly- mediating short-latency FRA reflexes. The organisa- synaptic (for references, see Hunt & Perl, 1960), and tionoflong-latencyFRApathwayssuggeststhatthey this was confirmed by intracellular recordings from play a role in the generation of locomotor stepping motoneurones (R. Eccles & Lundberg, 1959;Holmqvist & The above responses can be generated by stimu- Lundberg, 1961). Further investigations showed that lating cutaneous afferents in isolation. In addition, administration of DOPA in the acute spinal cat cutaneous afferents contribute to shaping the motor suppressed short-latency FRA responses, releasing output through their extensive convergence on transmission in a long-latency FRA pathway, which interneurones interposed in pathways fed by mus- had a half-centre organisation, capable of gener- cleafferentsorcorticospinalvolleys(cf. Chapters3–7 ating alternating activation of extensors and flexors and 10), and onto PAD interneurones mediat- (Jankowska et al. However, when cutaneous and FRA volleys elicit different effects in Initial findings the same motoneurone(s), there is evidence for a specialised cutaneous pathway. Investigations of spinal reflexes received impetus from the work of Sherrington (1906, 1910)onthe Reflexes elicited by low-threshold nociceptive flexion reflex. He showed that, in the cutaneous afferents spinalised decerebrate animal, noxious skin stim- The toe extensor reflex of the cat uli excite flexors and inhibit extensors in the ipsilat- eral hindlimb (the flexion reflex), accompanied by This is the most clear-cut example of a specialised excitation of extensors and inhibition of flexors in cutaneous reflex. Gentle pressure on the central the contralateral limb (the crossed extension reflex). The ensuing movement gives rise to an impulse flow in FRA which is channelled back into the reflex already activated, so that its activity is reinforced and prolonged (see p. From data in Engberg (1964)(a), and modified from Schouenborg (2002)(b), Lundberg (1973, 1979)((c), (d)), and Baldissera, Hultborn & Illert (1981)(e), with permission. Background from animal experiments 387 response in the plantar flexors of the toes (i. This reflex is due ingmotoneurones,presumablydesignedfordiscrete to the activation of slowly adapting mechanorecep- movementsofthedifferentdigits(Sasakietal. This extensor activation Cutaneousreflexesduringlocomotionarealsomedi- is appropriate to avoid the stimulus. Inchronicspinal specific relationship between receptive field, acti- cats walking on a treadmill, tactile stimuli applied to vated muscle(s) and the resulting reflex withdrawal thedorsumofthepawevokeshort-latencyresponses has been revealed both in the rat and the cat (for involving the flexors during the swing phase, but review, see Schouenborg, 2002). The responses in ate cutaneous receptive field corresponding to the knee muscles are stronger and have shorter laten- skin area withdrawn by contraction of the partic- cies than those of ankle and hip muscles.

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