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B. Ugolf. New York Academy of Art.

Court decisions after the 1960s generally nal activity rose dramatically in urban areas generic 10 mg alavert mastercard, have required that an individual be a danger to concern grew in the legal and medical commu- himself or herself or others before the legal sys- nities because increased incarceration had tem can use involuntary commitment (e 10 mg alavert with amex. In 1958 purchase alavert online, a joint committee of the In New York, death rates associated with the American Bar Association and the American injection of heroin increased from 7. In the 1960s prescribing opioids to treat addiction be estab- and 1970s, more than 150,000 names were lished on a controlled experimental basis added to the (Brecher and Editors 1972). Other groups voiced support for the concept of Support for opioid (The Narcotics opioid maintenance programs. The New York Register, active Academy of Medicine recommended, in 1955 from 1967 to 1974, and again in 1963, that clinics be established in maintenance grew, was a list of known affiliation with hospitals to dispense opioids in a or suspected persons controlled manner to patients addicted to illicit especially because with addictions. The istration greatly increased funding to stem the number of people number of serum supply of illicit opioids, primarily heroin, hepatitis (now entering the United States. It also greatly with opioid called hepatitis B) increased funding for methadone maintenance, cases related to con- and the number of patients receiving methadone addictions. Support for opioid Record numbers of 16 Chapter 2 maintenance grew, especially because no effec- time for patients to remain stable (Brecher and tive psychosocial alternative existed to treat the Editors 1972). Origins of Opioid M aintenance Therapy Developm ent of m ethadone W ith short-acting opioids eliminated as options Developm ent of M edications for maintenance therapy, research focused on methadone. Methadone appeared to be longer To Treat Opioid Addiction acting and effective when administered orally. It also was selected on the basis of observations Early rationale for of its use in patients withdrawing from heroin m ethadone m aintenance and as an analgesic in the experimental treat- treatm ent ment of pain (Dole 1980, 1988). Dole, a specialist in of heroin, morphine, or methadone to assess metabolism at The Rockefeller University, duration of action. Proof of the efficacy of became chair of the Narcotics Committee of the methadone maintenance treatment depended Health Research Council of New York City. After studying the scientific, public health, and social ramifications of addiction in the city, he In an initial study, methadone was adminis- received a grant to establish a research unit to tered to two patients previously maintained on investigate the feasibility of opioid mainte- morphine. In preparing for this research, he read to 120 mg was established, patients could func- The Drug Addict as a Patient by Dr. During this with extensive experience treating patients who research, the following important findings were addicted to opioids. She was convinced about methadone maintenance were noted, all that these individuals could be treated within supporting its efficacy and benefits (Dole 1980, general medical practice. She also believed that 1988): many would have to be maintained on opioids for extended periods to function because a ï Patients did not experience euphoric, tran- significant number of people who attempted quilizing, or analgesic effects. Their affect abstinence without medication relapsed, in and consciousness were normal. Therefore, spite of detoxifications, hospitalizations, and they could socialize and work normally with- psychotherapy (Brecher and Editors 1972; out the incapacitating effects of short-acting Courtwright et al. Among others ï A therapeutic, appropriate dose of methadone joining the team was clinical investigator Dr. Also, levels for methadone over time, unlike for the short half-life of morphine required several morphine and other opioids; therefore, a injections per day, and, as tolerance developed, dose could be held constant for extended increasing amounts were needed over a short periods (more than 20 years in some cases). History of M edication-Assisted Treatm ent for Opioid Addiction 17 ï Methadone was effective when administered initiative to treat opioid addiction under the orally. Jerome Jaffe, who headed the hours, patients could take it once a day Special Action Office for Drug Abuse without using a syringe. Prevention in the Executive Office of the W hite ï Methadone relieved the opioid craving or House in the early 1970s. Jaffeís office hunger that patients with addiction described oversaw the creation of a nationwide, publicly as a major factor in relapse and continued funded system of treatment programs for illegal use. Methadone Association for the Treatment of Opioid maintenance became a major public health Dependence n. Naltrexone also may benefit with the cost averaging $7 returned for every some patients in the beginning stages of opioid dollar invested (Gerstein et al. Other patient groups day of treatment paid for itself (the benefits frequently have demonstrated poor compliance to taxpaying citizens equaled or exceeded the with long-term naltrexone therapy, mainly costs) on the day it was received, primarily because naltrexone neither eases craving for through an avoidance of crimeî (Gerstein et the effects of illicit opioids when used as direct- al. History of M edication-Assisted Treatm ent for Opioid Addiction 19 ï Methadone treatment was among the most ï Encourage programs to provide comprehen- cost-effective treatments, yielding savings of sive services, such as individual and group $3 to $4 for every dollar spent. It identified the greatest reductions in criminal activity such barriers as the publicís misperception of and drug selling, down 84 percent and 86 persons who are opioid addicted not as individ- percent, respectively, of any type of opioid uals with a disease but as ìotherî or ìdifferent,î addiction treatment studied. B]) amended that Services and must comply with regulations portion of the Controlled Substances Act man- established by the U. Attorney General dating separate registration for practitioners regarding security of opioid stocks and mainte- who dispense opioids in addiction treatment. Interest in accreditation grew because Substance Abuse and Mental Health Services of its emphasis on self-assessment and Administration 2003a; see also chapter 3). In addition, trends in national health care Regulation fueled movement toward accreditation. Several States eligibility, evaluation procedures, dosages, grant exemptions from State licensing take-home medications, frequency of patient requirements (called ìdeemed statusî) to visits, medical and psychiatric services, coun- accredited health care facilities. The new regulations acknowledged that addiction is a medical disorder not medical disorder As experience with amenable to one-size-fits-all treatment. They the effectiveness of recognized that different patients, at different not amenable to methadone grew, times, could need vastly different services. Coverage of naltrexone is short because its use Dosage Formseiusmod in the United States generally has been limited to easing withdrawal symptoms for a small portion of patients undergoing medically super- EfficacyUt enim vised withdrawal after maintenance treatment. Exhibit 3-1 provides ad minim information about these and other medications for opioid addiction Side Effects veniam quis treatment, including the year of their U. Qualified physicians may dispense care settings should help move medical mainte- or prescribe buprenorphine products for up to nance treatment of opioid addiction into main- 30 patients at a time under the provisions of stream medical practice. Any criteria of the Secretary under this subclause shall be established by regulation. Any such criteria are effective only for 3 years after the date on which the criteria are promulgated, but may be extended for such additional discrete 3-year periods as the Secretary considers appropriate for purposes of this subclause. Such an extension of criteria may only be effectuated through a statement published in the Federal Register by the Secretary during the 30-day period preceding the end of the 3-year period involved. Pharm acology of M edications Used To Treat Opioid Addiction 27 are opioid addicted. Patients with special needs Pharm acology and may require split methadone doses given more Pharm acotherapy than once daily. Therapeutically appropriate entering the body equals the amount being doses of these agonist medications produce excreted) of methadone usually is achieved in 5 cross-tolerance for short-acting opioids such as to 7. Unlike of methadone also attenuate or block the methadone, it cannot be administered daily euphoric effects of heroin and other opioids. Methadoneís body clearance rate varies patients who cannot take oral methadone, considerably between individuals.

H 16 • Mindfulness Medication Try it again and really focus on scrunching your eyes closed and feeling the tension in your eyes as well as around them effective 10 mg alavert. When you fix your concentration on doing something like this generic alavert 10 mg mastercard, I think you’ll find that it pushes any other thoughts of yesterday or tomorrow right out of your mind order cheap alavert online. Is it skiing, dancing, cooking, painting, gardening, photography or playing hockey? At those times when you’re deeply engrossed in a favourite activity does time stand still, or do other thoughts come into your consciousness? When you’re totally present in what you are doing, the only thoughts that exist tend to be about the activity you are engaged in. You already have the ability to quiet your mind and make it focus and that just happens to be a characteristic of the human mind that you can put to use for reducing your stress. I know what you’re saying is probably something like, “So scrunching my eyes reduces stress? As you’ve no doubt noticed during the preceding exercises, thoughts come and go very frequently. Most of us normally do not have the ability to consistently maintain concentration on one thought. Even if you’re generally feeling sad, angry, or happy, within a short time your mind will still drift from thought to thought. If each thought is that important and meaningful why don’t thoughts stay around longer than they do? The tricky thing about any thought is that while you find yourself immersed in it, it feels permanent. However, if you wait it out, often just a little longer, that thought will actually pass and then you’ll have, at least temporarily, a break from it. If you can think of your thoughts as clouds that form and change, vanish and reform, rather than as things that are true, absolute and permanent, it may help you to de-stress. A lot of what you’re thinking Meet Your Mind • 17 when you’re stressed is just a string of hypothetical ‘what-ifs’. When you bring some awareness to a particularly stressful moment, you can let the natural inclination of the mind to move on, work to your advantage. Now I’d like you to really consider how long a thought actually tends to last for you personally and whether or not it’s something that’s permanent and unchanging. Specifically, observe how long they last, how they change or jump around and how sometimes they just pass away and another thought comes up to take their place. Invisible chains Real as steel Full of form Thought is empty Thought has form Is thought empty form? When you start observing your thoughts, you might notice that they seem to arise spontaneously without an apparent thinker behind them. It may seem that your mind is working independently of you, or your conscious control. Bring your attention to your thoughts as they arise and keep in mind whether you’re consciously and intentionally producing these thoughts yourself, or whether they are just arising spontaneously. Close your eyes and this time notice if you’re H consciously and purposely producing your thoughts. If you were generating your thoughts why wouldn’t you know what your next thought was going to be? Your thoughts are like a game of dominos, one domino hitting another domino that then creates this train of thoughts. It’s as if the thoughts are being produced independently of any person behind them. What goes on in one thought, triggers a relationship to another thought that then presents itself. From your memory, the image triggers your history with and knowledge of, that type of bird. Something like the following internal conversation might take place: What a beautiful bird! It’s a real discovery to understand that, what’s on your mind is really just a flow of thoughts, each triggering the next, without any conscious activity, or sometimes even any real meaning, necessarily behind it. In response to an external or internal sensation, a thought arises, which triggers a memory of another event that then leads to a subsequent thought. Each thought is dependent on the preceding thought until a new sensation comes along. Thoughts are just reflections of a complex interplay between physiological and psychological activity and are based on your previous experiences and patterns. By recognizing that your thoughts actually occur independently, in a meandering and domino- like fashion, they should have less power over you. You can observe thought production as a process occurring outside of your conscious control, like your heartbeat, or your fingernail growth. Notice if there’s a connection between your thoughts and return to this chapter after H you’ve finished. We all have deeply embedded 20 • Mindfulness Medication memories of our experiences and there are multiple, unconscious, mental connections that occur between these memories. Practice In an attempt to train your mind to start becoming aware of the nature of your thoughts on a more regular basis, here are a few more exercises that I suggest you set some time aside to do every day. Whenever a thought arises and you’re consciously aware of it, simply note to yourself the word ‘thinking’. Take five to ten minutes in the morning before getting up, or in the evening before going to sleep, to observe your mind and its thoughts. Sometimes this exercise is harder to do if you’re tired but see what works best for you. Observe how your thoughts arise spontaneously, are often connected to the preceding thought and are impermanent in nature. Focus on the idea that ‘your thoughts are not you, they are just passing through’. Pick something that will serve as a cue for you that occurs during your average day and use it as a reminder to simply observe your thoughts for a moment before you act on them, just as you’ve been doing throughout this chapter. Your cue could be as simple as sitting down to eat a meal, getting ready to go for a walk, picking up your phone to make a call, going into the bathroom, sitting in your car for a moment before driving, whatever works for you. Stick a Post-it note up somewhere to remind you that it’s your intention to focus on your thoughts in that situation. In this Ichapter, I’m going to have you take a look at how these thoughts can link together habitually in what becomes your own personal belief system. A belief system is really just a pattern of stories that you have been taught or have learned since childhood, or that you have developed in response to your own experiences. It’s how you frame and understand the things that you encounter in the world around you. You have created a personal belief system about everything you have ever come across, every new discovery, every interaction and every activity, in order to fit things in with what you already know.

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The response of these defenses to infection thus involves the correlation of a number of different mechanisms alavert 10 mg visa. Primary discount alavert 10 mg with amex, innate defects are rare generic alavert 10 mg with mastercard, whereas acquired, sec- ondary immune defects occur frequently, paving the way for infections by microorganisms known as “facultative pathogens” (opportunists). The terms pathogenicity and virulence are not clearly defined in their relevance to microorganisms. It has been proposed that pathogenicity be used to characterize a particular species and that virulence be used to describe the sum of the disease-causing properties of a population (strain) of a pathogenic species (Fig. Determinants of Bacterial Pathogenicity and Virulence Relatively little is known about the factors determining the pathogenicity and virulence of microorganisms, and most of what we do know concerns the disease-causing mechanisms of bacteria. Host–Pathogen Interactions 11 Virulence, Pathogenicity, Susceptibility, Disposition 1 virulent strain avirulent type or var (e. The terms disposi- tion and resistance are used to characterize the status of individuals of a suscep- tible host species. There are five groups of potential bacterial contributors to the pathogen- esis of infectious diseases: 1. Adhesion When pathogenic bacteria come into contact with intact human surface tis- sues (e. This is a specific process, meaning that the adhesion structure (or ligand) and the receptor must fit together like a key in a keyhole. Bacteria may invade a host passively through microtraumata or macrotraumata in the skin or mucosa. On the other hand, bacteria that invade through intact mucosa first adhere to this anatomical barrier, then actively breach it. Different bacterial species deploy a variety of mechanisms to reach this end: — Production of tissue-damaging exoenzymes that destroy anatomical bar- riers. Bacteria translocated into the intracellular space by endocytosis cause actin to condense into filaments, which then array at one end of the bacterium and push up against the inner side of the cell membrane. This is followed by fusion with the membrane of the neighboring tissue cell, whereupon the bacterium enters the new cell (typical of Listeria and Shigella). Strategies against Nonspecific Immunity Establishment of a bacterial infection in a host presupposes the capacity of the invaders to overcome the host’s nonspecific immune defenses. The most important mechanisms used by pathogenic bacteria are: Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Capsule components may 1 block alternative activation of complement so that C3b is lacking (ligand for C3b receptor of phagocytes) on the surface of encapsulated bacteria. Microorganisms that use this strategy include Streptococcus pneumoniae and Haemophilus influenzae. A lipopolysaccharide in the outer membrane is modified in such a way that it cannot initiate alternative activation of the complement system. As a result, the membrane attack complex (C5b6789), which would otherwise lyse holes in the outer membrane, is no longer produced (see p. They complex with iron, thereby stealing this element from proteins containing iron (transferrin, lactoferrin). The intricate iron transport system is localized in the cytoplasmic membrane, and in Gram- negative bacteria in the outer membrane as well. The free availability of only about 10–20 mol/l iron in human body fluids thus presents a challenge to them. At this stage of development, the immune system is un- able to recognize bacterial immunogens as foreign. Molecular mimicry refers to the presence of molecules on the surface of bacteria that are not recognized as foreign by the im- mune system. Examples of this strategy are the hyaluronic acid capsule of Streptococcus pyogenes or the neuraminic acid capsule of Escherichia coli K1 and serotype B Neisseria meningitidis. Mucosal immunity to gonococci depends on antibodies in the secretions of the urogenital mucosa that attach to the immunodominant seg- ment of the pilin, thus blocking adhesion of gonococci to the target cells. The gonococcal genome has many other pil genes besides the pilE without promoters, i. Intracellular homologous recombination of conserved regions of silent pil genes and corre- sponding sequences of the expressed gene results in pilE genes with changed cas- settes. Some bacteria are characterized by a pronounced variability of their immunogens (= immune antigens) due to the genetic variability of the structural genes coding the antigen proteins. This results in production of a series of antigen variants in the course of an infection that no longer “match” with the antibodies to the “old” antigen. Examples: gonococci can modify the primary structure of the pilin of their attachment Kayser, Medical Microbiology © 2005 Thieme All rights reserved. The borreliae that cause relapsing fevers have the capacity to change the structure of one of the adhesion proteins in their outer 1 membrane (vmp = variable major protein), resulting in the typical “recur- rences” of fever. Similarly, meningococci can change the chemistry of their capsule polysaccharides (“capsule switching”). Mucosal secretions contain the secretory antibodies of the sIgA1 class responsible for the specific local immunity of the mucosa. Classic mucosal parasites such as gonococci, meningococci and Haemophilus influ- enzae produce proteases that destroy this immunoglobulin. Clinical Disease The clinical symptoms of a bacterial infection arise from the effects of dama- ging noxae produced by the bacteria as well as from excessive host immune responses, both nonspecific and specific. Immune reactions can thus poten- tially damage the host’s health as well as protect it (see Immunology, p. Obligate intracellular parasites (rickettsiae, chlamy- diae) may kill the invaded host cells when they reproduce. Pathogenic bacteria can produce a variety of toxins that are either the only pathogenic factor (e. One aspect the clas- sification and nomenclature of these toxins must reflect is the type of cell affected: cytotoxins produce toxic effects in many different host cells; neu- rotoxins affect the neurons; enterotoxins affect enterocytes. The structures and mechanisms of action of the toxins are also considered in their classifica- tion (Table 1. They consist of a binding subunit “B” responsible for binding to specific surface receptors on target host cells, and a catalytic subunit “A” representing the active agent. These toxins disrupt biological membranes, either by attaching to them and assembling to form pores, or in the form of phos- pholipases that destroy membrane structure enzymatically. These antigens stimulate T lymphocytes and macrophages to produce excessive amounts of harmful cytokines. Proteolytic Increased muscle (Clostridium (synapses) cleavage of protein compo- tone; cramps in tetani) nents from the neuroexo- striated muscula- cytosis apparatus in the syn- ture. They must then be secreted through the cytoplasmic membrane, and in Gram-negative bacteria through the outer membrane as well. This interaction results in the opening of a secretion channel of the so-called “needle complex” (ex- tending through both the cytoplasmic Outer membrane and outer membrane) and membrane in formation of a pore in the mem- brane of the target cell. Through Periplasmic space the pore and channel, cytotoxic mole- cules are then translocated into the Inner membrane cytosol of the target cell where they, for example, inhibit phagocyto- sis andcytokine production (in macro- phages), destroy the cytoskeleton of the target cell, and generally work to induce apoptosis. The endotoxin of Gram-negative bacteria (lipopolysaccharide) 1 plays an important role in the manifestation of clinical symptoms. On the one hand, it can activate complement by the alternative pathway and, by releas- ing the chemotactic components C3a and C5a, initiate an inflammatory reaction at the infection site.

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