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Vibrissa frequency tuning curves are shown in the upper panels (gray) safe 20 mg levitra soft erectile dysfunction low blood pressure, and neural frequency tuning curves in the lower panels (black) levitra soft 20 mg fast delivery erectile dysfunction oil treatment. Right When responses were normalized and summed across the arc, a peak in vibrissa amplitude and neural activity was observed at ~400 Hz. This example highlights the coding of isofrequency information within an arc of vibrissae. Rather, the importance of the frequency map likely derives from the relative position of activation of columns of neurons in response to different frequency inputs — more posterior activation indicating relatively lower frequencies of presentation. One classical argument for the utility of a place code, based on increased mean firing rate, is that it circumvents the need for fine temporal following of high frequency input. Mammalian auditory systems can routinely process signals of several kHz or higher. The refractory period of a typical neuron prevents the fol- lowing of signals in this range. It remains an open question whether the vibrissae encounter and discriminate signals in the kHz frequency range, where place coding might be essential for adequate information transfer, and whether and how temporal encoding may contribute to high frequency perception. Even if the vibrissae only encode information accurately in the range of hundreds of Hz, a mean firing rate place code relieves the need to encode high frequency information in the precise timing of individual neurons. VELOCITY SENSITIVITY AND VIBRISSA RESONANCE Neurons throughout the vibrissa sensory system show robust velocity sensitivity. Inhibitory Neural Tuning in Rat SI For sinusoidal stimuli, velocity increases as (frequency x amplitude). If neurons are sensitive to the increased velocity of vibrissa motion generated by vibrissa resonance, then they should demonstrate a broadening of their tuning curve on its high frequency side and/or a shift in the peak of neural tuning to a higher frequency. This behavior was observed in the average trigeminal, FSU and multi-unit activity (MUA) tuning curves recorded in our previous study (Figures 2. However, RSU tuning curves did not show a velocity bias, as their average tuning curve was symmetric with a peak centered on the peak of vibrissa resonance. This symmetry may be explained as the result of intracortical sharpening by FSU activity – FSUs respond strongly and at a shorter latency to high frequency stimuli, and are, therefore, well positioned to inhibit RSU responses26 (see Figure 2. Whatever the mechanism, excitatory neuron activity in an SI barrel reflects the frequency tuning of vibrissa motion amplitude, and not velocity tuning, potentially providing relatively precise frequency coding that reflects vibrissa amplification. Velocity Sensitivity: Impact on the Representation of Specific Frequency Bands Diamond and colleagues recently presented a subset of high-frequency stimuli to multiple vibrissae simultaneously while recording MUA activity in SI. We similarly observed that, for a given amplitude of vibrissa stimulation, many single neuron and MUA responses demonstrated high-pass sensitivity in addition to vibrissa resonance tuning (Figure 2. High-pass frequency/velocity sensitivity has several potential impli- cations for the neural representation of vibrissa resonance. First, it suggests that those vibrissae that have a resonance tuning peak closer to the velocity threshold for the neuron being recorded will be more likely to evoke neural activity (Figure 2. Second, those vibrissae with lower fun- damental resonance frequencies will require greater amplification to reach the veloc- ity threshold (Figure 2. Third, those * While it remains an open question whether neurons in the vibrissa sensory system are sensitive to “velocity” or to some other factor that co-varies with velocity, we will follow the trend in the literature and will use the term velocity as shorthand for this class of features. This is because of a ceiling effect as these motions are already effective in driving robust neural activity and there is little dynamic range in the mean firing rate remaining to allow the expression of resonance-related tuning (Figure 2. An important implication of this framework is that, for any given amplitude of stimulation, vibrissae with intermediate resonance tuning frequencies may be in the proper range to evoke neural resonance tuning. In our previous experiments, pre- liminary data suggested that the 1 to 3 arcs demonstrated the highest incidence of observable resonance-related neural tuning and that MUA responses showed the greatest sensitivity to these velocity interactions, i. A second implication of the apparent saturation of mean firing rate at high velocities of stimulation is that a secondary coding mechanism, beyond resonance or velocity sensitivity — e. HIGHER HARMONICS: IMPLICATIONS FOR THE VIBRISSA RESONANCE HYPOTHESIS Higher harmonics of vibrissa motion may also generate high frequency/high velocity input to the vibrissa sensory system. In our previous studies,26,28 we did not system- atically characterize higher harmonics for a variety of study-design and methodolog- ical reasons. Nevertheless, we observed multiple examples of higher harmonics and many of these evoked neural activity. While the importance of higher harmonics remains to be assessed, several factors suggest that they may not play a major role in perceptually relevant neural trans- duction. First, because a vibrissa approximates a tapered conical beam, the impact of higher harmonics should be diminished relative to the impact predicted in other structures (e. First, they sparsely sampled frequency space, such that the distance between any two frequencies sampled (e.

Neocortical representational dynamics in adult primates: implications for neuropsychology generic levitra soft 20mg amex discount erectile dysfunction pills. The Neuro-physiology and Psychology of Hand Movements buy levitra soft 20 mg erectile dysfunction medications that cause, San Diego, CA: Academic Press, 381–414. Cholinergic depletion prevents expansion of topographic maps in soma-tosensory cortex. The reorganization of somatosensory cortex following peripheral nerve damage in adult and developing mammals. Focal dystonia following soft tissue injury: three case reports with long-term outcome. Psychological approach to focal dystonia in musicians, chapter 18, 363-368 in Tubiana R, Amadio PC. Medical Problems of the INstrumentalists Musician, Martin Dunitz Pub, 2000, 626 pp. Reorganization in the cutaneous core of the human thalamic principal somatic sensory nucleus (Ventral caudal) in patients with dystonia. Idiopathic torsion dystonia: Assignment of a gene to chromosome 18p in a German family with adult onset, autosomal dominant inheritance and purely focal distribution. Advances in Handwriting and Drawing: A Multidisciplinary Approach, Paris, France: Europia. Somatosensory representation of the digits and clinical performance in patients with focal hand dystonia, Am J Phys Med Rehabil, 2003, 82(10) 737-749. Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation. Progres- sion of change following median nerve section in the cortical representation of the hand in areas 3b and 1 in adult owl and squirrel monkeys. Development and maintenance of cortical somatosensory representations: Functional “maps” and neuroanatomical repertoires. Cortical plasticity underlying perceptual, motor, and cognitive skill development: implications for neurorehabilitation: Implications for neurorehabilitation. Some neuro- logical principles relevant to the origins of—and the cortical plasticity based reme- diation of—language learning impairments. In: Grafman J, Christen Y, (Eds) Neuroplasticity: Building a Bridge from the Laboratory to the Clinic. Murase N, Kaji R, Shimazu, H, Katayama-Hirota, M, Ikeda, A, Kohara, N, Kimura, J, Shibasaki, H, Rothwell, JD. Practice-related improvements in somatosensory interval discrimination are temporally specific but generalize across skin location, hemi-sphere, and modality. Long-latency reflexes of hand muscles in idiopathic focal dystonia and their modification by botulinum toxin. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Reorganization of movement representations in pri- mary motor cortex following focal ischemic infarcts in adult squirrel monkeys. Role of sensory deficits in motor impairments after injury to primary motor cortex. H-reflex recovery curve and reciprocal inhibition of H-reflex in different kinds of dystonia. Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. Perlmutter JS, Stambuk MK, Markham J, Black KJ, McGee-Minnich L, Jankovic J, Moerlein SM. Pujol, J, Roset-Llobet, J, Rosines-Cubells, D, Deus, J, Narberhaus, B, Valls-Sole, J, Capdevila, A, Pascual-Leone, 2000 A. Brain cortical activation during guitar-induced hand dystonia studied by functional MRI. Progressive improvement in discriminative abilities in adult owl monkeys performing a tactile frequency discrimination task. Topographic reorganization of the hand representation in cortical area 3b of owl monkeys trained in a frequency-discrimination task. Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a.

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The message that could be drawn was that the Police service showed high interest in the concept cheap levitra soft 20mg visa erectile dysfunction guilt in an affair, the Ambulance service maintained an interest and stated they were constrained by staffing problems effective levitra soft 20mg best erectile dysfunction pills review, whilst the Fire service effectively failed to engage with the other emergency services. This application of open space also highlights the assumptions about freedom to express ideas and thoughts along with assumptions about communicative competence and power and status, that were found in the previous three case studies. However, this example demonstrates that the process made transparent the level of commitment of two participating organisations. The application of interactive planning was essentially a chaired discussion group that addressed issues raised by the chair and those that others chose to contribute. The group at the two sessions was composed of a small number of experts in the areas of IT and HR drawn together specifically to address the perceived problems of the different organisations working together. As such there was no suggestion that they were designed to be representative or open to wider attendance. They were strongly controlled and tightly focused, intended only to identify potential problems rather than seeking any decisions Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Again the events were designed to inform the consultants exploration of the issues. This final case sought to apply a mix of approaches within one case intervention to fine tune the overall method, addressing the issues raised in cases 1-4. Critical Systems Heuristics (CSH) was chosen for its ability to deal with power, Open Space (OS) for its open, collaborative, unstructured qualities, and Interactive Planning (IP) to address a particular need within the information management of the project. CSH proved hugely valuable in surfacing issues of power and coercion, but less adept at dealing with them. OS seemed to work well with those organisations which chose to take part, but two organisations withdrew! Interactive Planning did its job well, but was a fairly tightly constrained part of the project. Endnote • Barfordshire is a pseudonym, and represents two adjoining counties containing two police, two fire and one ambulance service. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. David Johnson, University of Kentucky, USA Abstract The Cancer Information Service is a knowledge management organization, charged with delivering information to the public concerning cancer. This chapter describes how societal trends in consumer/client information behavior impact clinical knowledge management. It then details how the CIS is organized to serve clients and how it can interface with clinical practice by providing referral, by enhancing health literacy, by providing a second opinion, and by giving crucial background, assurance to clients from neutral third party. The CIS serves as a critical knowledge broker, synthesizing and translating information for clients before, during, and after their interactions with clinical practices; thus enabling health professionals to focus on their unique functions. Introduction The Cancer Information Service (CIS) is essentially a knowledge management (KM) organization, manifestly charged with delivering up-to-date information to the public Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Organizing for Knowledge Management 235 related to scientific advances concerning cancer. Its latent purpose, increasingly important in a consumer driven medical environment, is to insure the rapid diffusion of state-of-the-art medical care. It is an award-winning national information and education network, which has been the voice of the National Cancer Institute (NCI) for more than 30 years in the US. While the CIS has extensive outreach programs dedicated to reaching the medically underserved, it is probably best known for its telephone service that has a widely available 800 number (1-800-4-CANCER). We will use the CIS as an exemplar in this chapter of issues related to a national information infrastructure that supports clinical knowledge management. Because of the critical role of broader societal trends we will turn to a discussion of them before describing in more detail the basic services and organizational structure of the CIS and its potential interfaces with clinical KM. Many health organizations have realized that there are strategic advantages, especially in enhancing quality, maintaining market share, and developing innovations, in promoting information technologies. Improving information management, associated analytic skills, and knowledge utilization should be a top priority of clinical practice (Johnson, 1997).

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The concentrations in the central nervous system (CNS) and cerebrospinal fluid are gen- Isoniazid (isonicotinic acid hydrazide generic levitra soft 20 mg line bpa causes erectile dysfunction, or INH) is the erally about 20% of plasma levels but may reach close most active drug for the treatment of tuberculosis to 100% in the presence of meningeal inflammation safe levitra soft 20 mg erectile dysfunction otc treatment. It is a synthetic agent with Isoniazid is acetylated to acetyl isoniazid by N-acetyl- a structural similarity to that of pyridoxine. Individuals who are genetically rapid acetylators will have Mechanism of Action a higher ratio of acetyl isoniazid to isoniazid than will slow Isoniazid is active against susceptible bacteria only when acetylators. The may continue to undergo one or two divisions before slow or rapid acetylation of isoniazid is rarely important multiplication is arrested. Isoniazid can inhibit the syn- clinically, although slow inactivators tend to develop pe- thesis of mycolic acids, which are essential components of ripheral neuropathy more readily. The mycobacterial enzyme cata- azid and small amounts of unaltered drug are excreted in lase–peroxidase KatG activates the administered isoni- the urine within 24 hours of administration. The target sites for the Clinical Uses activated isoniazid action are acyl carrier protein AcpM and Kas A, a -ketoaceyl carrier protein synthetase that Isoniazid is among the safest and most active mycobac- blocks mycolic acid synthesis. It is also included in the Antimicrobial Activity first-line drug combinations for use in all types of tu- berculous infections. The minimal tuberculostatic inhibitory concen- action with no radiological or other clinical evidence of tration (MIC) of isoniazid is 0. Mycobacterium kansasii is usually suscep- tible to isoniazid, and it is included in the standard mul- Resistance tidrug treatment regimen. Risk factors for hepatitis include underlying liver therapeutic levels are achieved in all body fluids, in- disease, advanced age, pregnancy, and combination cluding cerebrospinal fluid. Early recognition and ducing its own metabolism, so its half-life can be re- prompt discontinuation of the drug is recommended to duced to 2 hours within a week of continued therapy. The deacetylated form of rifampin is active and under- Peripheral neuropathy is observed in 10 to 20% of goes biliary excretion and enterohepatic recirculation. Most of the drug is excreted into the GI tract and a Patients with underlying chronic disorders such as alco- small amount in the urine. Moderate dose adjustment is holism, malnutrition, diabetes, and AIDS are at particu- required in patients with underlying liver disease. Isoniazid promotes renal excretion of pyridoxine, treatment of all forms of pulmonary and extrapul- resulting in a relative deficiency and neuropathy. Rifampin is an alternative to iso- toxicity may range from excitability and seizures to psy- niazid in the treatment of latent tuberculosis infection. The neurotoxic effects are reversed without al- Rifampin also may be combined with an antileprosy tering the antimycobacterial action by the administra- agent for the treatment of leprosy and to protect those tion of 10 to 50 mg/day of pyridoxine. Drug Interactions High isoniazid plasma levels inhibit phenytoin metabo- Adverse Reactions lism and potentiate phenytoin toxicity when the two The most commonly observed side effects are GI dis- drugs are coadministered. The serum concentrations of turbances and nervous system symptoms, such as nau- phenytoin should be monitored, and the dose should be sea, vomiting, headache, dizziness, and fatigue. It is a large lipid- zymes, leading to an increased metabolism of many soluble molecule that is bactericidal for both intracellu- drugs; this action has especially complicated the treat- lar and extracellular microorganisms. Rifampin binds ment of tuberculosis in HIV-infected patients whose reg- strongly to the -subunit of bacterial DNA-dependent imen includes protease inhibitors and nonnucleoside re- RNA polymerase and thereby inhibits RNA synthesis. Antibacterial Activity and Resistance Hypersensitivity reactions, such as pruritus, cuta- In addition to M. Rifampin resistance results from a point mutation or Rifampin imparts a harmless red-orange color to urine, deletion in rpoB, the gene for the -subunit of RNA feces, saliva, sweat, tears, and contact lenses. Patients polymerase, thereby preventing the binding of RNA should be advised of such discoloration of body fluids. Rifampin is well absorbed orally, and a peak serum con- Its exact mechanism of action is not known, although centration is usually seen within 2 to 4 hours. Drug ab- its target appears to be the mycobacterial fatty acid 560 VI CHEMOTHERAPY synthetase involved in mycolic acid biosynthesis. Ethambutol has replaced aminosalicylic acid as a Pyrazinamide requires an acidic environment, such as first-line antitubercular drug. It is commonly included as that found in the phagolysosomes, to express its tuber- a fourth drug, along with isoniazid, pyrazinamide, and culocidal activity. A mutation in the The major toxicity associated with ethambutol use is gene (pncA) that encodes pyrazinamidase is responsi- retrobulbar neuritis impairing visual acuity and red- ble for drug resistance; resistance can be delayed green color discrimination; this side effect is dose re- through the use of drug combination therapy.

Such com- (or theophylline) may present some problems if the pounds are often referred to as wake-up tablets discount levitra soft 20mg on-line impotence causes and symptoms, but drug is given too rapidly cheap 20mg levitra soft mastercard impotence young. In such cases, severe headache, these methylxanthine-containing products do little to hypotension, and palpitation accompany drug adminis- offset physical fatigue, so they place individuals using tration. Diuresis Abuse of Xanthines All the xanthines, but especially theophylline, are capa- ble of producing some degree of diuresis in humans. The use of some xanthine-containing beverages is cus- This specific action of the methylxanthines is discussed tomary in most cultures, and moderate use of such bev- in greater detail in Chapter 21. For example, it has been observed that chronic coffee drinkers who suddenly abstain fre- Theophylline is frequently used as a bronchodilator in quently have headaches and a general feeling of fatigue the treatment of asthma. Although it has not been methylxanthines in the management of bronchial established that these symptoms constitute any kind of asthma is discussed more fully in Chapter 39. There is as the citrate salt (Cafcit) is used for the short-term no good evidence for the development of tolerance to management of apnea in premature infants (28–33 the CNS stimulant effects of caffeine. Cardiac Uses Drug Interactions Theophylline, given as the soluble ethylenediamine salt An interaction of potential clinical significance involves aminophylline, offers some help in relieving the parox- the xanthines and the coumarin anticoagulants. Xanthines ysmal dyspnea that is often associated with left heart by themselves shorten clotting time by increasing tissue failure. A major portion of its efficacy may be due to the prothrombin and factor V and in this regard may be ex- relief of bronchospasm secondary to pulmonary vascu- pected to antagonize the effectiveness of oral anticoagu- lar congestion. Opisthotonos is a convulsive condition that is often (D) Antagonism of muscarinic receptors in the associated with the ingestion of strychnine. This heart condition is associated with all of the following (E) Blockade of ganglionic transmission at sympa- EXCEPT thetic ganglia in the periphery (A) Antagonism of the inhibitory amino acid neu- rotransmitter glycine ANSWERS (B) The predominance of glycine as an inhibitory 1. Glycine is the major inhibitory amino acid trans- amino acid transmitter in the spinal cord mitter in the spinal cord, and strychnine is a rela- (C) Antagonism of the inhibitory amino acid neu- tively selective antagonist of glycine. Strychnine has rotransmitter GABA very little if any action at the GABA receptor– (D) The convulsions lead to tonic extension of the chloride channel complex. Which of the following classes of agents is useful tention deficit disorder are among only a few ap- in the treatment of attention deficit hyperkinetic proved uses of the psychomotor stimulants of the disorder? Analeptic stimulants, such as pentylenetetrazol (B) Benzodiazepines and picrotoxin, act by inhibiting chloride influx at (C) Xanthines the GABAA receptor–chloride channel complex. However, the concen- GABA receptor–chloride channel complex tration of cAMP that is required for such action is (B) Increased release of catecholamines from CNS above the threshold of CNS stimulation. Since the neurons methylxanthines are relatively potent antagonists of (C) Inhibition of cholinesterase leading to in- adenosine and since adenosine has been shown to creased acetylcholine levels be a reasonably potent inhibitor of both central and (D) Antagonism of CNS adrenoceptors to reduce peripheral neurons, the most likely mechanism by inhibition produced by catecholamines which CNS stimulation occurs is through antago- (E) Antagonism of nicotinic receptors that inhibit nism of adenosine receptors. The CNS stimulation produced by methylxanthines, are also indirectly acting sympathomimetics that in- such as caffeine, is most likely due to the antago- crease the release of catecholamines from sympa- nism of which of the following receptors? While amphetamine and (A) Glycine receptors other congeners possess additional actions on pe- (B) Adenosine receptors ripheral sympathetic nerves, this is the most likely (C) Glutamate receptors explanation for the cardiac stimulation observed (D) GABA receptors following the administration of these agents. Cardiac stimulation is an adverse effect associated with the use of the psychomotor stimulants, such as SUPPLEMENTAL READING amphetamine. From GABAA receptor diversity emerges a (C) Inhibition of a GABA-mediated negative unified vision of GABAergic inhibition. What types Wnessman who often spends long hours at the of pathological conditions can lead to excessive office or in his automobile traveling to meet new somnolence? Sleep apnea is characterized by pauses in the past several years, the number of daytime respiration during sleep and usually excessive snor- episodes has begun to increase, and he recently be- ing. Patients with sleep apnea have EDS but often gan to lose mobility in his arms and legs during the awake without feeling rested. Your examination re- clearly defined by determining whether he has a veals an individual who is in otherwise excellent specific human leukocyte antigen associated with health and mentation with no apparent significant the disorder (HLA-DR2). He indicates that he has several periods colepsy is accomplished with psychomotor stimu- of EDS during the day and that the frequency of lants of the amphetamine type. While he feels modafinil, pemoline, and dextroamphetamine all are well rested upon waking, he is especially concerned effective in managing the EDS periods, while about the recent loss of skeletal muscle function imipramine and clomipramine can be used to man- and fears that he may be developing some degener- age any cataplexy. Dailey DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Alprazolam 357 Lorazepam 357 Buspirone 356 Midazolam 359 Chloral hydrate 361 Oxazepam 357 Chlordiazepoxide 359 Prazepam 357 Clonazepam 359 Propranolol 361 Clorazepate 357 Temazepam 357 Diazepam 359 Triazolam 357 Flurazepam 357 Zephalon 360 Hydroxyzine 361 Zolpidem 360 The primary use of sedative–hypnotic and anxiolytic relieve symptoms of anxiety only at doses that produce drugs is to encourage calmness (anxiolytics or sedatives) noticeable sedation. All people are and relieve anxiety are consistently among the most subject to states of emotional tension and uneasiness. Whether they are pre- For otherwise healthy individuals, these occasions are scribed too frequently remains a matter of controversy.

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