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By: Joseph St. Geme, MD

  • Chair, Department of Pediatrics, Professor of Pediatrics and Microbiology, Perelman School of Medicine at the University of Pennsylvania
  • Physician-in-Chief, Leonard and Madlyn Abramson Endowed Chair in Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania


We can put reperfusion injury in perspective by emphasizing that there are three different degrees of cell injury symptoms brain tumor 40mg paxil with visa, depending on the duration of the ischemia: · With short periods of ischemia medications with weight loss side effect purchase cheap paxil line, reperfusion (and medicine in motion generic paxil 20 mg with mastercard, therefore symptoms you have diabetes order paxil 30mg amex, the resupply of oxygen) completely restores the structural and functional integrity of the cell. In this case, cell damage does not depend on the formation of activated oxygen species. Viral Cytotoxicity Is Direct or Immunologically Mediated the means by which viruses cause cell injury and death are as diverse as viruses themselves. Unlike bacteria, a virus requires a cellular host to (1) house it; (2) provide enzymes, substrates, and other resources for viral replication; and (3) serve as a source for dissemination when mature virions are ready to be spread to other cells. Viruses have evolved mechanisms by which they avoid biting the hand that feeds them (at least until they are ready for other hands). The ability of a virus to persist in an infected cell necessitates a parasitic, albeit temporary, relationship with the host cell. During this vulnerable phase, the virus plays a game of cat and mouse with the immune system as a device to evade elimination of the infected cell. This period is followed by a phase in which the virus disseminates, either by budding (which does not necessarily destroy the cell) or by lysis (which does). The mechanisms underlying virus-induced lysis of cells, however, are probably more complex. Ionizing Radiation Causes Oxidative Stress the term "ionizing radiation" connotes an ability to cause radiolysis of water, thereby directly forming hydroxyl radicals. For a nonproliferating cell, such as a hepatocyte or a neuron, the inability to divide is of little consequence. For a proliferating cell, however, the prevention of mitosis is a catastrophic loss of function. Once a proliferating cell can no longer divide, it dies by apoptosis, which rids the body of those cells that have lost their prime function. Whereas exposure to significant sources of radiation impairs the replicating capacity of cycling cells, massive doses of radiation may kill both proliferating and quiescent cells directly. Direct injury caused by virus infection, involving both depletion of cellular resources and activation of apoptotic signaling mechanisms. Mechanisms that lead to immunologically mediated destruction of virus-infected cells. Since viruses must avoid cell death before they have produced infectious progeny, they have evolved mechanisms to counteract this effect by upregulating anti-apoptotic proteins and inhibiting proapoptotic ones. Some viruses also encode proteins that induce apoptosis once daughter virions are mature (see. These arms of the immune system eliminate virus-infected cells by inducing apoptosis or by lysing the cell with complement (see. Chemicals Injure Cells Directly and Indirectly Innumerable chemicals can damage almost any cell in the body. The science of toxicology attempts to define the mechanisms that determine both target cell specificity and the mechanism of action of such chemicals. Toxic chemicals either: (1) interact directly with cellular constituents without requiring metabolic activation or (2) are themselves not toxic but are metabolized to yield an ultimate toxin that interacts with the target cell. Liver Necrosis Caused by the Metabolic Products of Chemicals excess it is highly toxic to the liver. Most acetaminophen is enzymatically converted in the liver to nontoxic glucuronide or sulfate metabolites. In addition, acetaminophen metabolism is accelerated by chronic alcohol consumption, an effect mediated by an ethanol-induced increase in the 3A4 isoform of P450. To summarize, metabolism of hepatotoxic chemicals by mixed-function oxidation leads to cell injury through covalent binding of reactive metabolites and peroxidation of membrane phospholipids. Chemicals That Are Not Metabolized Directly cytotoxic chemicals interact with cellular constituents: prior metabolic conversion is not needed. These studies have focused principally on those compounds that are converted to toxic metabolites. Each is metabolized by the mixed-function oxidase system of the endoplasmic reticulum and each causes liver cell necrosis. These hepatotoxins are metabolized differently, and it is possible to relate the subsequent evolution of lethal cell injury to the specific features of this metabolism. Abnormal G Protein Activity Leads to Functional Cell Injury Normal cell function requires the coordination of numerous activating and regulatory signaling cascades. Hereditary or acquired interference with correct signal transduction can result in significant cellular dysfunction, as illustrated by diseases associated with faulty G proteins. Inherited defects in G protein subunits can lead to constitutive activation of the protein. In one such hereditary syndrome, endocrine manifestations predominate, including multiple tumors in the pituitary and thyroid glands. Another G protein mutation appears to predominate in many cases of essential hypertension, in which exaggerated activation of G protein signaling results in increased vascular responsiveness to stimuli that cause vasoconstriction. Decreased responsiveness of G proteins to ligand­receptor interactions may also be caused by certain mutations in G protein subunits. In addition, G protein activity can be inhibited by certain bacterial products, the most important example being pertussis toxin, the cause of whooping cough. Although the mechanisms responsible for necrosis vary according to the nature of the insult and the organ involved, most instances of necrosis share certain mechanistic similarities. The model of necrotic cell death that has been studied most extensively in mechanistic terms is ischemic injury to cardiac myocytes. The sequence of events is admittedly unique to cardiac myocytes, but most features are pertinent to other cell types and injurious agents. Necrosis is the Process by Which Exogenous Stress Kills the Cell Cells exist in a skewed equilibrium with their external environment. The plasma membrane is the barrier that separates the extracellular fluid from the internal cellular milieu. Whatever the nature of the lethal insult, cell necrosis is heralded by disruption of the permeability barrier function of the plasma membrane. Normally, extracellular concentrations of sodium and calcium are orders of magnitude greater than intracellular concentrations. The selective ion permeability requires (1) considerable energy, (2) structural integrity of the lipid bilayer, (3) intact ion channel proteins, and (4) normal association of the membrane with cytoskeletal constituents. When one or more of these elements is severely damaged, the resulting disturbance of the internal ionic balance is thought to represent the "point of no return" for the injured cell. By contrast, cytosol Ca2 concentration is 10,000-fold lower, on the order of 10 7 M. Many crucial cell functions are exquisitely regulated by minute fluctuations in cytosol free calcium concentration. Thus massive influx of Ca2 through a damaged plasma membrane ensures loss of cell viability. Coagulative Necrosis Cell Death An understanding of the mechanisms underlying cell death is not simply an academic exercise; manipulation of cell viability by biochemical and pharmacologic intervention is currently a major area of research. For example, if we understand the biochemistry of ischemic death of cardiac myocytes, which is responsible for the leading cause of death in the Western world, we may be able to prolong myocyte survival after a coronary occlusion until circulation is restored. Physiologic cell death is integral to the transformation of embryonic anlagen to fully developed organs. It is also crucial for regulation of cell numbers in a variety of tissues, including the epidermis, gastrointestinal tract, and hematopoietic system. Physiological cell death involves activation of an internal suicide program, which results in cell killing by a process termed apoptosis. By contrast, pathologic cell death is not regulated and is invariably injurious to the organism. Necrosis occurs when an insult interferes with a vital structure or function of an organelle (plasma membrane, mitochondria, etc. Pathologic cell death, however, can also result from apoptosis, as exemplified by viral infections and ionizing radiation. Coagulative necrosis refers to light microscopic alterations in a dead or dying cell. When stained with the usual combination of hematoxylin and eosin, the cytoplasm of a necrotic cell is more deeply eosinophilic than usual.

Participants either had existing vascular disease (coronary medications at 8 weeks pregnant order cheap paxil on line, cerebral or peripheral) or were at risk of such disease (because of smoking symptoms jaw cancer order paxil pills in toronto, hypertension or diabetes) symptoms tracker order paxil 20mg amex. The primary endpoint was a composite of coronary death treatment 197 107 blood pressure buy discount paxil 40 mg on-line, non-fatal myocardial infarction, and fatal and nonfatal stroke. Four studies met these criteria: the Lipid Research Clinic Primary Prevention Trial, the Helsinki Heart Study, the West of Scotland Coronary Prevention Study, and the Air Force/Texas Coronary Prevention Study (318, 319, 327, 328). Lipid-lowering drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0. When the analysis was limited to trials that used statins a slightly stronger effect on all outcomes was found, but there was still no significant reduction in all-cause mortality (although none of these studies was individually powered for this endpoint). Another review of lipid-lowering treatment with statins found that coronary heart disease events and all-cause mortality were reduced in primary prevention populations (329). This review, unlike the meta-analysis mentioned above (326), did not include the large Air Force/Texas trial, which was conducted later. It included the Kuopio atherosclerosis prevention study, a trial in which about 10% of subjects had a history of myocardial infarction (330), and which was not included in the more recent meta-analysis. Data from 15 trials with 63 410 participants and a mean duration of treatment of 3. Overall, statin treatment reduced the relative risk of coronary events, cardiovascular disease mortality, non-fatal strokes and all-cause mortality. There was a 23% reduction in myocardial infarction and coronary death, a 24% reduction in the need for coronary revascularization, and a 17% reduction in fatal and non-fatal strokes, giving a 21% reduction overall in major cardiovascular events. In some trials, participants had high blood pressure, diabetes or ischaemic heart disease. Statins reduced ischaemic heart disease events at age 60 by an estimated 61% in the long term; there was little reduction in the first year but a 51% reduction by the third year. They also reduced the overall risk of stroke by 17%, preventing thromboembolic stroke but not haemorrhagic stroke. Any possible excess of haemorrhagic stroke was greatly outweighed by the protective effect against ischaemic heart disease events and thromboembolic stroke. Twelve randomized placebo-controlled double-blind trials, with a follow-up of at least 3 years, were included. The analysis confirmed that patients, whether diabetic or not, benefit from lipid-lowering in accordance with their absolute cardiovascular risk. The evidence for efficacy of other lipid-lowering agents in primary prevention is weak. This was a mixed primary and secondary prevention study, which randomly assigned 2131 patients with previ- 48 Prevention of cardiovascular disease ous cardiovascular disease and 7664 without to receive either fenofibrate or a placebo. At 5 years follow-up, fenofibrate did not significantly reduce the risk of coronary events. While statins and resins had a significant lipid-lowering effect, n-3 fatty acids did not significantly affect cholesterol levels. Although there is little reason to believe that the effects would be different in non-Europeans with similar baseline risks of cardiovascular disease and similar lipid profiles, research is needed to examine the effects of lipid-lowering treatment in other racial groups. Risks There is no evidence from the large studies that cholesterol-lowering therapy increases the risk of death from other causes (333, 337, 338). Meta-analysis of data from statin trials has not shown an excess of adverse symptoms, including muscle pain and various gastrointestinal symptoms, in the treated group. Rhabdomyolysis (indicated by serum creatine kinase 10 times the upper limit of normal) was reported in 55 treated patients (0. The incidence of rhabdomyolysis is estimated to be about one per million person­years of use. Hepatitis (indicated by alanine aminotransferase 3 times the upper limit of normal) was reported in 449 treated patients (1. Data from randomized trials of cholesterol reduction and disease events have not provided evidence that a low serum cholesterol concentration increases mortality from any cause, other than possibly haemorrhagic stroke. Too few haemorrhagic strokes were observed in the randomized trials to resolve the uncertainty related to this condition. Further, the risk of haemorrhagic stroke affected only people with a very low cholesterol concentration and, even in this group, the risk was outweighed by the benefits from the reduced risk of coronary heart disease. In the Cholesterol Treatment Trialists Collaboration meta-analysis, there was no evidence of an effect on cancer deaths. The reduction in major vascular events was as marked in these elderly patients as in those aged under 65 years. However, there was an apparent excess of non-melanoma skin cancer in the simvastatin-treated group, compared with the placebo group (2. In the Scandinavian Simvastatin Survival Study (342), 21 patients in the statin group developed non-melanoma skin cancer, compared with seven in the placebo group. Overall, there is no statistically significant evidence that statin therapy increases the incidence of cancer. Treatment of those most at risk will bring the most benefit; treatment of patients not at high risk of cardiovascular disease may expose them to adverse effects without much benefit. As the side-effects of liver and muscle damage are dosedependent (340), the high-dose statin regimens evaluated in some of the trials (344) will have a worse side-effects profile when applied to patients treated in everyday clinical practice. Fibrates reduced the risk of major coronary events by 25% and niacin by 27% (349). However, recent studies have not found a cholesterol level below which there is no benefit, suggesting that taking a trial-validated dose of a statin is more important than aiming for a particular target cholesterol level (321). Thus, continued monitoring of blood lipids may not be necessary in settings with limited resources. Primary prevention trials (320, 322, 323) have demonstrated that patients at highest total risk of cardiovascular events obtain the greatest benefit from statin therapy. Treatment should therefore be targeted at the group with highest total risk, rather than simply those with highest lipid levels. Cost-effectiveness, feasibility and resource implications of antihypertensive and statin therapy the cost-effectiveness of a treatment is determined by the relationship between the benefits obtained and the expenditure. The prevalence of a condition and the total cost of treating it in a specific setting, on the other hand, determine affordability. Because resources are limited, even a cost-effective treatment may not be affordable. The two main determinants of cost-effectiveness are the cost of drug therapy and the initial cardiovascular risk of the patient. In the case of antihypertensive treatment, the major classes of antihypertensive drugs are largely equivalent in terms of efficacy. However, diuretics and beta-blockers, singly or in combination, are associated with an increased incidence of diabetes; thus, in populations with an increasing burden of diabetes, other classes of antihypertensive therapies may be preferable. In most parts of the world, a diuretic is the cheapest option and is, therefore, generally most cost-effective. However, for certain compelling indications, other classes will provide additional benefits; even if they are more expensive, they may be more cost-effective. There is no evidence to support claims of superior performance of any particular drug within each of the major drug classes. As populations age, increasing numbers of elderly people are being diagnosed as hypertensive and requiring treatment. For this group, diuretic-based therapy is the most cost-effective; therapy that includes either atenolol or low-dose reserpine has been shown to be a relatively inexpensive approach to prevention of cardiovascular events in older adults with isolated systolic hypertension (351). Although people over the age of 75 years get less benefit from statin therapy, such therapy is cost-effective for people in all age groups with a 10-year cardiovascular risk of 20% or more (352, 353). Thus, if the decision is made to initiate statin therapy, the least expensive statin should usually be chosen. Control of glycaemia Issue Does control of glycaemia reduce cardiovascular risk in patients with diabetes? Evidence Cardiovascular disease accounts for about 60% of all mortality in people with diabetes. The risk of cardiovascular events is 2­3 times higher in people with type 1 or type 2 diabetes (354, 355) and the risk is disproportionately higher in women (354, 356).

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There is always friction: meaning not like an object transported and dropped into a new place medicine descriptions order paxil canada, but meaning like skin it bears scars treatment 5th metatarsal fracture purchase paxil with mastercard, rips and tears symptoms gallstones discount paxil 40 mg amex, hydrated nourished and worn treatment impetigo 20 mg paxil amex. Enke edited the collection Transfeminist Perspectives in and beyond Transgender and Gender Studies (2012) and is working on a graphic novel titled ``With Finn and Wing: Growing Up Amphibious in a Nuclear Age. Kang, Tobaron Waxman, the Electronic Disturbance Theater, Chris Vargas, Cayden Mak, and Jacolby Satterwhite, have created works that express dimensions of transgender and gender-nonconforming experience while also transforming the relationship between the aesthetics, politics, and technologies of cultural representation. In their transmedia productions, bodies, images, sounds, materialities, politics, and informatics offer points of social contact and expressive meaning making rather than static representations and theories. These practitioners engage transmedia critically by paying attention to shifting networks of interrelated references, such as masculine and feminine, surface and essence, migrant and citizen; race, region, ethnicity, and nationality; urban, suburban, and rural; post- and nonindustrial; human, animal, plant, and thing. In the War of Desire and Technology at the Close of the Mechanical Age (1996), Stone explains how the act of listening to a public lecture by Stephen Hawking, amplified through microphone, computer, and speakers, can create a communicative intimacy that trespasses the presumed boundaries of the body and internal self. For Stone, communications technology and the gendered body itself are virtual ``prostheses' that provide zones of active social interaction, boundary shifting, and communicated meaning (ibid. In response to the epistemic violence of academic knowledge production, Stone has turned to performance as her primary medium of knowledge transmission, emphasizing the impact of sharing space, time, and physical presence in specific contexts (Stone 2010). This real-time action in performance produced a layered media insurgency that destabilized academic paradigms of knowledge production and ownership. Subversive transmedia exploits, undermines, and overwrites corporate uses of the same term by ``post'-industrial transnational Hollywood. As a commercial concept, transmedia describes contemporary media products that are created through models of production and for models of consumption that differ from mass industrial modes. Transmedia products are hybrids that cross and connect multiple media narrative threads, genres, and forms. They are produced, circulated, and consumed across interconnected media industries and technologies within the United States and transnationally. The hybrid products created through managed transnational media networks promise diverse yet coordinated entertainment experiences for different audiences-and greater profit for media corporations-through multiple avenues of consumption. New Zealand was an outsourced and economically incentivized filming location for Avatar. The location was also a source of labor and an ecological resource (the basis for the virtual world of Pandora) for the film. The interpenetration of media industries and technologies produces phantasmagorias, or simulated sensory connections between products that overload and alienate the senses so that consumption becomes passive (Buck-Morss 1991). A reclaimed transmedia approach recognizes that commercial intoxication relies on sustaining the out-of-world feeling of having been transported across space and time. Becoming aware of our participation in these time-space warps, or ``wormholing dynamics,' can jolt us out of sensory alienation (King 2012). Trans and genderqueer rebels mobilize transmedia to recover the deleted material conditions that have enabled the current technological and economic networking of media. What has been called the ``digital revolution' describes the transformation of late nineteenth- to mid-twentieth-century mass media technologies, including newspapers, magazines, radio, television, and film, by new media technologies that rely on computational devices and the Internet as a backbone for communicative networking (Chun and Keenan 2005). The shift from ``old' to ``new' media has helped to facilitate a broad transition from mass industrial economies based in manufacturing in the global North to a new global economy based on services, leisure, and entertainment. Critical transmedia approaches interrupt corporate and state narratives on the purely democratizing effects of new media and the new ``weightless' political economy that it has created. The ``virtual' network infrastructure does not only rely on conductors (cables, towers, satellites), nodes (connecting points, protocols, Downloaded from read. It also depends on a labor-intensive economy that includes creative work along with cassiterite mining, semiconductor manufacturing, the the production and laying of fiber-optic cables in regions of Africa, Latin America, and Asia (Ekine 2010). Revealing the hidden labor of the transnational bodies found on the integrated circuit is mandatory for a critical understanding of global media networks and commerce. Their/his research focuses on new strategies for transgender, queer, and gender and sexual nonconforming cultural activism at the turn of the twenty-first century, with the transition from cultural politics to cultural economies facilitated by networked media technologies. Lissette Olivares is a PhD candidate in the History of Consciousness Department at the University of California, Santa Cruz, where she investigates the role of new media in social movements from a transnational and transhistorical perspective. Almost any trans person can attest to the existence of it based on personal experiences or the experiences of acquaintances. And there is documented evidence of sexual violence, physical violence, and verbal harassment of trans people, and at least the self-reports of trans people indicate that such behavior often arises from hostile attitudes toward them as trans. However, the exact rates, nature, and extent of violence are difficult to determine, in part because there are no reliable statistics on how many trans people there are and because the various methods for collecting these data have specific limitations (Stotzer 2009). While it is clear transphobia exists, however, it is far from evident what transphobia is. Provisionally, the term can be defined to mean any negative attitudes (hate, contempt, disapproval) directed toward trans people because of their being trans. Transphobia occurs in a broader social context that systematically disadvantages trans people and promotes and rewards antitrans sentiment. It therefore has a kind of rationality to it, grounded in a larger cisgenderist social context (Hopkins 1996). In doing this, I have tried to avoid smuggling an actual account of the underlying nature of transphobia into the definition. If it is defined as ``those who violate gender norms,' or as ``those who are problematically positioned with respect to the gender binary,' then a very general account of the nature of transphobia is immediately forthcoming-namely, transphobia is a hostile response to perceived violations of gender norms and/or to challenges to the gender binary. It is not wise, however, to build a robust account of transphobia into the definition. A trans woman may not view herself as violating norms of gender, and Downloaded from read. Rather, she may see herself as a woman living within the binary and in accordance with norms of womanhood. A robust definition of this type ironically invalidates her gender identity in order to function as an account of transphobia. I therefore prefer to leave trans people undefined and open to the multiple, contested meanings. Consequently, while transphobia is provisionally defined, one of the central components of that definition (trans people) is not only undefined but left open to multiple interpretations. Underlying the attempt to build a robust account of transphobia within the definition of the term is the problematic assumption that there is a singular phenomenon of which there can be a uniform account. Consider that while the pronoun it can be used to deny the personhood of individuals deemed outside the binary categories, the expression really a man disguised as a woman effectively accuses a trans person of pretense by deeming them within one of the binary categories. Both are instances of verbal harassment, and both can function as ``justifications' for physical violence. But that the latter concerns a response to perceived violations of the binary is surely controversial. Whether there is a singular phenomenon here (hostile responses to perceived violations of the binary) is therefore far from clear. For example, Latin American representations of trans people as deceivers may include stronger associations with criminality (Lewis 2010). Indeed transphobia can occur differently in different types of social contexts within a culture. In therapeutic contexts it is not uncommon for trans people to be viewed as mentally ill. The view that ``mental illness' is the paradigmatic stigma elides different forms of stigma applied to trans people for whom access to medico-psycho-therapeutic narratives is irrelevant. And the controversial expectation that there is a single phenomenon is precisely what helps promote treatment of specific kinds of transphobia as somehow exemplary. Finally, the view that transphobia can be separated from other enactments of power (such as sexism, classism, racism) is a nonstarter. This means that not all acts of violence against trans people need be transphobic in nature. A trans woman might be targeted not because of her trans status but because she is simply viewed as a sex worker (Namaste 2005). Moreover, at least in some cases, transphobia may be inseparably blended with misogyny or racism in ways that challenge a single-axis model of power (Juang 2006). Such inseparabilities undermine the attempt to account for transphobia in a way that excludes or marginalizes considerations of sexism, racism, classism, ableism, and so forth. This consideration is important because it questions why certain instances of violence should Downloaded from read.


Patients began to medicine 512 order paxil once a day see other purposes medications affected by grapefruit purchase paxil 20mg visa, other values symptoms xanax abuse discount 10 mg paxil with visa, other meaning and pleasures in their lives symptoms vitamin b deficiency order line paxil, grew more self-confident and balanced, more emotionally open and self-sufficient, and more responsible for their lives and the lives of their loved ones (Krupitsky & Grinenko, 1997). The team designed a double-blind randomized clinical trial comparing the relative effectiveness of a high psychedelic dose of ketamine (2. The preliminary 6-month follow up demonstrated that a hallucinogenic (psychedelic) dose of ketamine was more effective than a non-hallucinogenic (sub-psychedelic) dose. Two-year follow-up data confirmed that the rate of abstinence in the high-dose ketamine group was significantly higher than that in the low-dose control group, while the corresponding rate of relapse was lower (Krupitsky et al. Interestingly, many of the measured change variables did not differ significantly between high and low dose groups. This suggests that the psychotherapy common to both groups played an important role in the observed effects. This could also be the effect of set and setting combined with a relatively low dose of ketamine. Once again, no differences between groups were found in anxiety, depression, the severity of craving for heroin, or their understanding of the meaning of their lives. The data from this study provide some evidence that treatment-resistant patients who did not experience a mystical state of consciousness during the initial ketamine session may benefit from a second or even a third ketamine session. It also proved to be efficacious in the treatment of stimulant dependence, as well as a very effective modality for the treatment of comorbid psychiatric conditions, such as posttraumatic stress disorder, neurotic depression, anxiety disorders, and avoidant personality disorders. These encouraging clinical results occurred because of positive changes in the life values and purposes, relationships, and worldviews of these patients. They showed a transformation of emotional attitudes, a decrease in the level of inner discord, internal tension, discomfort, and emotional isolation; improved self-assessment; and a tendency to overcome the passive aspects of their personalities. Subsequently, ketamine abuse among Russian youth rapidly escalated from the late 1990s. Ketamine remains available only for anesthesia and conscious sedation at the present time in Russia. In the preparation stage, preliminary psychotherapy is carried out with patients, who are told that the psychedelic session may induce important insights concerning their personal problems, their system of values, their notions of self and the world around them, and the meaning of their lives. Patients are educated that all of these insights may lead to positive changes in their personalities, which will be important for healing their underlying problems and shifting to a sober lifestyle. At least five to ten hours of psychotherapy are provided before the ketamine session in order to establish the psychospiritual goal for the transpersonal experience and prepare the subject for the session. Breakfast is omitted on the morning of ketamine administration, and all participants refrain from food and drink for at least eight hours prior to this experience. Patients are told that they will enter some unusual states of consciousness and are instructed to surrender fully to the experience. After the patient lies down in a comfortable supine position with eyeshades, ketamine is injected intramuscularly, in doses from 2. The intramuscular route is preferred because the onset is more gradual and the psychedelic experience lasts longer. With a background of specially chosen music, generally free-floating non-associative classical or New Age, the patient typically has a powerful non-ordinary state of consciousness, frequently resembling a mystical experience. During the recovery period, which takes from one to two hours, the patient begins to feel ordinary reality returning. At this point in the session, the patient usually begins to describe the experience and some discussion and interpretation is begun with the psychotherapist. The patient is asked to write down a detailed self-report of the transpersonal ketamine experience that evening (Krupitsky & Grinenko, 1997; Krupitsky & Kolp, 2007). The third stage is the integration of the ketamine-induced experience, which is carried out after the ketamine session. It is generally done in a group psychotherapy format, because the dynamic of the shared group experience appears more powerful and therapeutic than individual therapy alone. From three to five hours of psychotherapy are provided after the ketamine session to help subjects interpret and integrate their experiences during the session into everyday life. With the aid of the psychotherapist during the integration phase of treatment, the patients discuss and interpret the personal significance of the symbolic content of their ketamineinduced non-ordinary state of consciousness. This discussion is directed toward helping the patients make a correlation between their psychedelic experience and their intra- and interpersonal problems. The therapist O assists the patients in the psychological integration of the spiritual transformation that can result from the direct transpersonal experience. This uniquely profound and powerful experience often helps patients to generate fresh insights that enable them to integrate new, often unexpected meanings, values, and attitudes about the self and the world (Krupitsky & Grinenko, 1997; Krupitsky & Kolp, 2007). It should be explicitly pointed out that a ketamine-induced psychedelic experience may have only marginal and transitory beneficial effects in and of itself, no beneficial effects at all, or may be harmful when ketamine is used in uncontrolled settings recreationally. It can sometimes lead to significant medical problems and addiction (Jansen, 2000, 2001; Jansen & DarracotCanckovic 2001; Ricuarte, 2005). The therapeutic relationship, as well as set and setting, are paramount to the effectiveness of ketamine psychedelic psychotherapy. Eli Kolp is a bi-cultural psychiatrist and was originally trained in the former U. After Kolp requested that the Soviet authorities allow him to emigrate from the U. Even with the most intensive longterm treatment, which included multiple sessions of an unpleasant aversive conditioning, more than 75% of Russian alcoholics relapsed on alcohol within one year after completion of treatment. After Kolp immigrated to the United States in 1981, he successfully re-trained as a private psychiatrist and began practicing general adult and geriatric psychiatry. Circa 1990, Kolp returned to the treatment of addictive illnesses, both in private and public sectors, where he directed various outpatient, residential, and inpatient programs specializing in the treatment Ketamine Psychedelic Psychotherapy International Journal of Transpersonal Studies 103 of alcohol, drug, and/or food addiction. He quickly learned that efforts to treat alcoholism in the American population are costly and have a low rate of recovery, as they do in Russia. A previous meta-analysis of outcomes of treatment for alcoholism (Nathan, 1986) showed that different treatment methods did not appear to be associated with significantly different long-term outcomes. It was reported that treatment factors, including theoretical orientation, content, locus, and intensity of treatment revealed little or no difference in treatment outcome, despite great differences in costs. Although abstinence rates one year after treatment may reach 40% to 50% for persons with good treatment prospects (well-motivated, employed, sub-chronic alcoholics with a large network of support and substantial personal resources treated at private treatment facilities), typical abstinence rates for poorly motivated, unemployed, chronic alcoholics with a limited network of support and few personal resources seen at public treatment facilities were 25% or less. Rates of abstinence at and beyond the two-year mark are often less than 50% of the rates of abstinence at the one-year mark. In the United States, Kolp, inspired by Krupitsky, thus began working towards utilizing ketamine psychedelic psychotherapy in 1994. Haley Veterans Hospital in Tampa, Florida, and then by the Research and Development Committee of the Department of Veterans Affairs. It was further approved by the Research Committee of the Department of Psychiatry at the University of South Florida College of Medicine and the Institutional Review Board of the University of South Florida Health Science Center. Unfortunately, the implementation of the protocol never materialized due to a lack of the institutional support and an absence of research funds. The patients were males and females, 21-64 years old, who identified alcohol as their drug of choice and satisfied the diagnostic criteria for alcohol dependence. He continued utilizing group psychotherapy in a residential setting 104 International Journal of Transpersonal Studies Kolp et al. In addition, Kolp continued utilizing individual psychotherapy on an outpatient basis for treatment of existential anxieties in terminally ill people and selected patients with addictive disorders who did not wish to participate in a residential treatment program, or could not tolerate a group process. Instead, they desired to undertake only pharmacotherapy with a low subpsychedelic dose of ketamine. However, she abandoned that denomination during her late teens, continuing as a non-denominational Christian. C began using alcohol at age 16, started drinking on a regular basis at age 18, and developed alcohol binges at age 25. Her binges lasted from 3-4 days to 2 weeks, every several weeks, with a consumption of nearly one liter of vodka a day during the binges. However, she never had a stable remission (her longest remission lasted 7 months, including 2 months in a rehabilitation program). C did not wish to participate in a group residential program and elected an individual outpatient treatment.

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