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Rifabutin has fewer interactions and may be nate if both drugs are given with phenytoin) order super p-force oral jelly 160mg with amex, and vincristine proven super p-force oral jelly 160mg. The PIs indinavir and nelfinavir and INH increases the risk of hepatotoxicity with most of these most of the NNRTIs can be used with rifabutin discount super p-force oral jelly 160 mg line. Ritonavir drugs; concurrent use should be avoided when possible or (PI) and delavirdine (NNRTI) should not be used with ri- blood levels of the inhibited drug should be monitored buy super p-force oral jelly 160 mg without prescription. Also purchase super p-force oral jelly 160 mg visa, amprenavir and indinavir increase risks of vincristine, INH may increase peripheral neuropathy. Dosage of rifabutin should be decreased if The rifamycins (rifampin, rifabutin, rifapentine) induce cy- given with one of these drugs. Rifampin is the strongest inducer and may decrease the Use in Children effects of angiotensin converting enzyme (ACE) inhibitors, anticoagulants, antidysrhythmics, some antifungals (eg, flu- Tuberculosis occurs in children of all ages. Infants and conazole), anti-HIV protease inhibitors (eg, amprenavir, indi- preschool children are especially in need of early recognition navir, nelfinavir, ritonavir), anti-HIV nonnucleoside reverse and treatment because they can rapidly progress from primary transcriptase inhibitors (NNRTIs; delavirdine, efavirenz, infection to active pulmonary disease and perhaps to extra- nevirapine), benzodiazepines, beta blockers, corticosteroids, pulmonary involvement. Tuberculosis is usually discovered cyclosporine, digoxin, diltiazem, doxycycline, estrogens and during examination of a sick child or investigation of the con- oral contraceptives, fexofenadine, fluoroquinolones, fluva- tacts of someone with newly diagnosed active tuberculosis. Children in close narcotic analgesics (eg, methadone, morphine), nifedipine, contact with a case of tuberculosis should receive skin testing, ondansetron, phenytoin, propafenone, rofecoxib, sertraline, a physical examination, and a chest x-ray. For treat- Rifabutin is reportedly a weaker enzyme inducer and may be ment of active disease, the prescribed regimens are similar to substituted for rifampin in some cases. That is, the same primary drugs are most often for clients who require anti-HIV medications. As in adults, drug-susceptible tuberculosis is treated Tuberculosis is a common opportunistic infection in people with INH, rifampin, and pyrazinamide for 2 months. Then, with advanced HIV infection and may develop from an ini- pyrazinamide is stopped and the INH and rifampin are con- tial infection or reactivation of an old infection. Both regimens may be given daily or twice susceptibility reports become available. Several cases of serious liver damage and a few not given, INH and rifampin are recommended for 9 months. Drug-resistant TB in children is usually acquired from an Treatment of active disease is similar to that of persons adult family member or other close contact with active, drug- who do not have HIV infection. For children exposed to MDR-TB, there is who adhere to standard treatment regimens do not have an in- no proven preventive therapy. Several regimens are used em- creased risk of treatment failure or relapse. Thus, these clients pirically, including ethambutol and pyrazinamide or ethion- are usually treated with antitubercular drugs for 6 months as amide and cycloserine. When INH and rifampin cannot be 572 SECTION 6 DRUGS USED TO TREAT INFECTIONS given because of MDR-TB, drug therapy should continue for early as possible, clients should be thoroughly instructed to 24 months after sputum smears or cultures become negative. Clients with MDR-TB may require months hepatotoxicity, serum ALT and AST should be measured be- of treatment before sputum smears become negative, and fore starting and periodically during drug therapy. To guide dosage and occurs, these enzymes usually increase before other signs and minimize adverse drug effects, serum drug levels should be symptoms develop. If drug- Hepatitis and liver damage are more likely to occur during the resistant or extrapulmonary disease is suspected, 4 drugs are first 8 weeks of INH therapy and in middle-aged and older indicated. Clients should be assessed monthly for symptoms of Overall, as with adults, drug therapy regimens vary with hepatitis (anorexia, nausea, fatigue, malaise, and jaundice). Health care symptoms occur or if AST and ALT increase significantly providers must follow current recommendations of pediatric (more than five times the normal values), INH should be dis- infectious disease specialists. INH should be used cautiously in clients with pre- existing liver disease. With rifampin, liver damage is most likely to occur with Use in Older Adults preexisting liver disease or concurrent use of other hepato- toxic drugs. Clients should be monitored at least monthly for Although INH is the drug of choice for treatment of latent in- symptoms of hepatotoxicity. AST and ALT may be measured fection, its use is controversial in older adults. Because risks of before starting rifampin and periodically during rifampin drug-induced hepatotoxicity are higher in this population, therapy. If signs of liver damage occur, the drug should be some clinicians believe those with positive skin tests should stopped, serum AST and ALT should be measured, and med- have additional risk factors (eg, recent skin test conversion, im- ical evaluation should be done. When INH is given, people who drink alcoholic bever- with preexisting liver impairment unless it is considered ab- ages daily are most likely to sustain serious liver impairment.

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In addition cheap 160mg super p-force oral jelly free shipping, clients should be informed view form may be helpful in eliciting appropriate about common and potential adverse effects of drug information effective 160mg super p-force oral jelly. Monitoring during therapy is indi- with inconvenient hours buy super p-force oral jelly 160 mg online, long waiting times cheap super p-force oral jelly 160mg fast delivery, and un- cated for patients who have abnormal baseline values supportive staff) may deter clients from being evalu- or other risk factors for liver disease and those who ated for a positive skin test buy 160 mg super p-force oral jelly amex, initiating treatment, or develop symptoms of liver damage. Some clinicians completing the prescribed treatment and follow-up recommend that INH be stopped for transaminase care. Individualizing treatment regimens, when possible, ciated with symptoms and five times the upper limit to increase client convenience and minimize disruption of normal if the patient is asymptomatic. CHAPTER 38 DRUGS FOR TUBERCULOSIS AND MYCOBACTERIUM AVIUM COMPLEX (MAC) DISEASE 571 Effects of Antitubercular are HIV-seronegative clients. The regimen may be longer if Drugs on Other Drugs the bacteriologic (eg, negative cultures) or clinical response (eg, improvement in symptoms) is slow or inadequate. Isoniazid (INH) increases risks of toxicity with several drugs, A major difficulty with treatment of TB in clients with apparently by inhibiting their metabolism and increasing HIV infection is that rifampin interacts with many protease their blood levels. These include acetaminophen, carba- inhibitors (PIs) and nonnucleoside reverse transcriptase in- mazepine, haloperidol, ketoconazole, phenytoin (effects of hibitors (NNRTIs). If the drugs are given concurrently, ri- fampin decreases blood levels and therapeutic effects of the rifampin are opposite to those of INH and tend to predomi- anti-HIV drugs. Rifabutin has fewer interactions and may be nate if both drugs are given with phenytoin), and vincristine. The PIs indinavir and nelfinavir and INH increases the risk of hepatotoxicity with most of these most of the NNRTIs can be used with rifabutin. Ritonavir drugs; concurrent use should be avoided when possible or (PI) and delavirdine (NNRTI) should not be used with ri- blood levels of the inhibited drug should be monitored. Also, amprenavir and indinavir increase risks of vincristine, INH may increase peripheral neuropathy. Dosage of rifabutin should be decreased if The rifamycins (rifampin, rifabutin, rifapentine) induce cy- given with one of these drugs. Rifampin is the strongest inducer and may decrease the Use in Children effects of angiotensin converting enzyme (ACE) inhibitors, anticoagulants, antidysrhythmics, some antifungals (eg, flu- Tuberculosis occurs in children of all ages. Infants and conazole), anti-HIV protease inhibitors (eg, amprenavir, indi- preschool children are especially in need of early recognition navir, nelfinavir, ritonavir), anti-HIV nonnucleoside reverse and treatment because they can rapidly progress from primary transcriptase inhibitors (NNRTIs; delavirdine, efavirenz, infection to active pulmonary disease and perhaps to extra- nevirapine), benzodiazepines, beta blockers, corticosteroids, pulmonary involvement. Tuberculosis is usually discovered cyclosporine, digoxin, diltiazem, doxycycline, estrogens and during examination of a sick child or investigation of the con- oral contraceptives, fexofenadine, fluoroquinolones, fluva- tacts of someone with newly diagnosed active tuberculosis. Children in close narcotic analgesics (eg, methadone, morphine), nifedipine, contact with a case of tuberculosis should receive skin testing, ondansetron, phenytoin, propafenone, rofecoxib, sertraline, a physical examination, and a chest x-ray. For treat- Rifabutin is reportedly a weaker enzyme inducer and may be ment of active disease, the prescribed regimens are similar to substituted for rifampin in some cases. That is, the same primary drugs are most often for clients who require anti-HIV medications. As in adults, drug-susceptible tuberculosis is treated Tuberculosis is a common opportunistic infection in people with INH, rifampin, and pyrazinamide for 2 months. Then, with advanced HIV infection and may develop from an ini- pyrazinamide is stopped and the INH and rifampin are con- tial infection or reactivation of an old infection. Both regimens may be given daily or twice susceptibility reports become available. Several cases of serious liver damage and a few not given, INH and rifampin are recommended for 9 months. Drug-resistant TB in children is usually acquired from an Treatment of active disease is similar to that of persons adult family member or other close contact with active, drug- who do not have HIV infection. For children exposed to MDR-TB, there is who adhere to standard treatment regimens do not have an in- no proven preventive therapy. Several regimens are used em- creased risk of treatment failure or relapse. Thus, these clients pirically, including ethambutol and pyrazinamide or ethion- are usually treated with antitubercular drugs for 6 months as amide and cycloserine. When INH and rifampin cannot be 572 SECTION 6 DRUGS USED TO TREAT INFECTIONS given because of MDR-TB, drug therapy should continue for early as possible, clients should be thoroughly instructed to 24 months after sputum smears or cultures become negative. Clients with MDR-TB may require months hepatotoxicity, serum ALT and AST should be measured be- of treatment before sputum smears become negative, and fore starting and periodically during drug therapy.

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The cost of printed information can vary enor- mously order 160 mg super p-force oral jelly otc, and the key variable is knowledge of the techniques buy super p-force oral jelly 160mg mastercard. Put another way discount super p-force oral jelly 160 mg visa, you can spend an awful lot of money and produce something that is unreadable buy super p-force oral jelly 160mg low cost, and spend next to nothing and produce something that does precisely what you intended generic 160mg super p-force oral jelly mastercard. Usually they will be happy to advise out of goodwill; they may even find it therapeutic. Ignore the views of your colleagues – their comments will almost certainly be criticisms of the content rather than judgements over whether you are getting the right messages across. Test any information on the target audi- ences – ask your patients to read it and then ask for their comments. You could gently probe them to see whether they have taken home the messages that you intended them to take home (see payoff). Remember, this is not a test of your knowledge, but an attempt to put across some useful bits of information to people who are often frightened and confused, and delighted when they receive clear advice. Patronizing language One of the problems of writing, particularly for patients, is that if you use long words you are criticized for not being concise – and if you use short ones you are criticized for being patronizing. The tabloids, for instance, use this kind of language – and are rewarded by millions of readers daily. Where language becomes patronizing is not when the words are simple, but when certain phrases are introduced that define the reader as an outsider. In other words, there is an assumption that the reader will not understand. The solution, I suspect, lies not in changing our style but in having a more robust attitude. If it is your target readers who are complaining, then you can easily make changes. But most of the accusations tend to come from those who have appointed themselves to be their spokespeople (see false feedback loop). Peer review The system of peer review started in the mid- 17th century when scientists decided that, before they published an article, they should ask the opinion of others working in the same field. The assumption is that exposing work to the criticism of others will identify shortcomings and improve the quality of published material. It is a cornerstone of modern science publishing, with complicated structures developed to carry it out, and more recently a growing peer review research industry giving it added status. Most papers go through to the second stage, which is assessment by others in the field who are known to the journal. Finally the editor, or someone to whom he has delegated this task, will decide, singly or with the help of a committee, which ones to keep. Normally there are more that have passed the quality controls than there is room to publish, so the final decision is generally taken on a subjective decision as to which one(s) are more likely to appeal to the readers (see gut reaction). There have been three major international conferences over the past 10 years looking into peer review and medical journals. Much of 92 PEER REVIEW this research has looked into the best ways of running the system, and into variables such as whether the authors should be told of the reviewers, or the reviewers be told of the authors, or whether young doctors from America make better reviewers than middle-aged professors from Europe (the evidence is that they do). Indeed many of the important questions – such as whether the system can be used to detect scientific fraud, or whether editors would make substantially different decisions without the system – remain unanswered. All this, of course, is of marginal interest to most authors, who simply see the system as a major obstacle to publication. The system, for all its faults, is going to be with us for the foreseeable future, so the sensible approach is to learn how to manage it. The decision to publish rests with the editor and, although it will be helpful if you have pleased the reviewers, it is probably not a good idea to set out to do so. On the other hand, you do know who the editor will be – and by carefully studying the journal (see evidence-based writing), you will have a good idea of what he or she likes. Try to distinguish between reviewers who throw in additional facts and tamper with the style on the one hand, and those who give useful macro-editing feedback on the other. If you feel that the final decision rests on a mistake made by the reviewers, consider appealing (see dealing with rejection). Many writers spend hours complaining about the injustices of the system when they could be learning how to play the game.

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Experi- and assessment of forelimb sensorimotor outcome mental hemiplegia in the monkey: Basal ganglia glu- in unilateral rat models of stroke purchase super p-force oral jelly 160 mg otc, cortical ablation cheap super p-force oral jelly 160 mg amex, cose activity during recovery cheap super p-force oral jelly 160mg otc. Kipnis J discount super p-force oral jelly 160mg on line, Yoles E cheap super p-force oral jelly 160mg line, Schori H, Hauben E, Shaked I, and functional evidence for lesion-specific sprout- Schwartz M. Neuronal survival after CNS insult is ing of corticostriatal input in the adult rat. J Comp determined by a genetically encoded autoimmune Neurol 1996; 373:484–497. Strain eration and differentiation of progenitor cells in the and model differences in behavioral outcomes after cortex and the subventricular zone in the adult rat spinal cord injury in rat. Steward O, Schauwecker P, Guth L, Zhang Z, Fu- cortical lesions in the adult rat. J Neurosci 2002; jiki M, Inman D, Wrathall J, Kempermann G, Gage 22:6062–6070. Kornblum H, Araujo D, Annala A, Tatsukawa K, approaches to neurotrauma research: Opportunities Phelps M, Cherry S. In vivo imaging of neuronal ac- and potential pitfalls of murine models. Experi Neu- tivation and plasticity in the rat brain by high reso- rol 1999; 157:19–42. Bruce-Keller A, Umberger G, McFall R, Mattson sis after cortical photothrombosis in rat brain. Jin K, Mao X, Eshoo M, Nagayama T, Minami M, Trends Neurosci 2002; 25:295–301. Microarray analysis of 146 Neuroscientific Foundations for Rehabilitation hippocampal gene expression in global cerebral isch- adult monkey thalamus after peripheral nerve in- emia. Mas- spine number and type on pyramidal neurons of the sive cortical reorganization after sensory deaf- visual cortex of old adult rats from social or isolated ferentation in adult macaques. Learning causes synaptogenesis, tions to large-scale plasticity of primate somatosen- whereas motor activity causes angiogenesis, in cere- sory cortex. Science 1998; 282:1117– dendrites in adult rats recovering from neocortical 1120. Use-dependent growth of py- celerates recovery of locomotor function following ramidal neurons after neocortical damage. Hurwitz B, Dietrich W, McCabe P, Ginsberg M, drites and restoration of function after brain dam- Alonso O, Watson BD, Schneiderman N. Restor Neurol amine promotes recovery from sensory-motor inte- Neurosci 1994; 7:119–126. Humm J, Kozlowski D, James D, Gotts J, Schallert mary somatosensory rat cortex. Kozlowski D, von Stuck S, Lee S, Hovda D, Becker beam walking ability after sensorimotor cortex abla- D. Pharm Biochem Behav 2000; exaggeration of neuronal injury after unilateral sen- 67:473–478. Bland S, Schallert T, Strong R, Aronowski J, Grotta cumbens and cingulate cortex. Behav Brain Res 1992; 51: ticity in a model of cerebral hemispherectomy and 1–13. Recovery of function after on recovery from sensorimotor cortex lesions. Behav Brain Res mapping of human central motor representation on 1986; 20:1–18. The American Society for of the effects of unilateral removal of sensorimotor Neural Transplantation and Repair: Considerations cortex in infant monkeys. Chapter 3 Functional Neuroimaging of Recovery NEUROIMAGING TECHNIQUES Other Agents Positron Emission Tomography SUMMARY Single Photon Emission Computerized Tomography Functional Magnetic Resonance Imaging Neurophysiologic imaging follows structure Transcranial Magnetic Stimulation and function. Unlike the traditional model in Magnetoencephalography which the clinician associates an impairment High Resolution Electroencephalography with a focal lesion, functional neuroimaging of- Intrinsic Optical Imaging Signals fers insights that go beyond the region of dam- Near-Infrared Spectroscopy aged tissue. A systems level approach can be Magnetic Resonance Spectroscopy taken to identify sites of dysfunction even in Transcranial Doppler the absence of structural damage. Spared tis- Combined Methods sue can be identified physiologically, rather LIMITATIONS OF FUNCTIONAL than based on an anatomic guess.

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