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Effects of Propofol Analogs on Glucuronidation of Propofol, an Anesthetic Drug, by Human Liver Microsomes

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INTRODUCTION

UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of a broad spectrum of endobiotic and xenobiotic substrates . In general, the resulting glucuronides are more hydrophilic, facilitating renal and biliary excretion. In addition to hepatic metabolism, high rates of gastrointestinal glucuronidation in rats and humans have been observed . Propofol (2,6-diisopropylphenol) is administered as a bolus for the induction of anesthesia and as an infusion for maintenance of anesthesia or for sedation. A rapid and complete recovery is a major advantage of this drug, which is attributable to extensive biotransformation of the parent compound. Propofol is suggested to be a substrate for one of the UGT isoforms, UGT1A9 [6,7]. There is a hypothesis that propofol could be orally used with a suitable inhibitor among analogs for preventing its rapid glucuronidation [8]. In order to seek for a suitable inhibitor of propofol biotransformation, we investigated the interactions between propofol and its analogs in the glucuronidation by recombinant human...

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Sleep in the Substance Using Population

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The effect of any psychoactive substance on an individual’s sleep will depend on whether that substance is a stimulant, depressant, or has other effects on the brain. A schema is portrayed in Figure 1 (see page 842). The effect of withdrawal from the substance generally will be opposite to the intoxication effects. Psychoactive substances are classifi ed as sedative hypnotics, stimulants, opioids, hallucinogens, and arylcyclohexylamines.

EFFECTS OF SUBSTANCES ON SLEEP

Alcohol

Alcohol is perhaps the best-studied substance in connection with sleep disturbances. Studies show that 13% of the general population used alcohol in the past year to go to sleep, and The effect of any psychoactive substance on an individual’s sleep will depend on whether that substance is a stimulant, depressant, or has other effects on the brain. A schema is portrayed in Figure 1 (see page 842). The effect of withdrawal from the substance generally will be opposite to the intoxication effects. Psychoactive substances are classifi ed as sedative hypnotics, stimulants, opioids, hallucinogens, and arylcyclohexylamines.

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The Use of Curare in Anesthesia A Review of 100 Cases

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Good muscular relaxation is one of the requirements for efficient abdominal surgery, and in order to obtain this relaxation surgeons and anesthetists have sometimes used anesthetic drugs and methods which are toxic or hazardous. The introduction of curare into clinical medicine has made it possible for us to obtain complete muscular relaxation at any time during anesthesia with nontoxic controllable anesthetic agents. After more than two years of careful clinical observation I have come to the conclusion that curare is a safe drug to use in combination with certain anesthetic agents, provided it is administered under properly controlled conditions.

The story of the transformation of this South American Indian arrow poison into an anesthetist's tool may be told briefly as follows: Curare has been known to science since 1595, when Hakluyt referred to it in his description of Sir Walter Raleigh's voyage up the Orinoco. In 1840 Claude Bernard,

Additional Resource: Curare In Anesthesia

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Toxicology: Drugs and Poisons In Forensic Science

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1. Toxicology: Drugs and Poisons Forensic Science

2 Toxicology Toxicology - Mix of Chemistry and Physiology that deals with drugs, poisons, and other toxic substances. Began in 1775 when Swedish chemist Karl Scheele discovered a way to prove arsenic was the culprit in a suspicious death.

3 Poisons ANY substance that when taken in sufficient quantities causes a harmful or deadly reaction. (Sufficient quantities how much enters the body, over what period of time) . Intoxicant requires an ingestion of large quantities before it is lethal Ex: Carbon Monoxide, Alcohol, heavy metals (mercury, lead, selenium) 2. True Poison requires only a tiny amount - Ex: Cyanide

4 The Forensic Toxicologist Finds toxins and determines the likely effect on the individual who ingested or came in contact with it. Examples: Inebriation in an automobile accident or industrial accident Whether a person died from poison or from natural cause? Whether drugs played a role in a perpetrator’s actions or in seizures or coma?...

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Speedball and Crack Injection in London | Groins, Veins and Injecting Environment

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Speedball and crack injection in London groins, veins and injecting environment THE CENTRE FOR RESEARCH ON DRUGS AND HEALTH BEHAVIOUR Tim Rhodes Jo Kimber, Daniel Briggs, Vivian Hope, Greg Holloway, Steve Jones

2 crack and groin injecting Six City Study in England, n=952, 2003/2004, Hope et al o n=952, six locations o 45% groin injecting o 40% crack/speedball injecting o > 70% crack injection Bristol & Manchester, and > 50% London [Judd et al., 2005] o crack injectors more likely to be groin injectors (49% vs 34%) o groin injectors more likely to have an open wound infection (26% vs 18%) and DVT in last year (28% vs 8%) Rhodes et al. (2006) “Groin injecting in the context of crack cocaine and homelessness”, International Journal of Drug Policy, 17: 164-170.

4 qualitative study speedball injectors (n=44), Bristol and London, 2006 median age, 33 (range 23-53) male, 75% homeless in past year, 69% speedball in past month, 80% mean years speedball, 7 (<1-23 years)...

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The Urgent Case for Immediate Treatment of Propofol as a Controlled Substance in All Clinical Settings

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Propofol has been reported as a drug of abuse amongst anesthesia providers since 1992. As an uncontrolled substance, propofol is seldom kept in locked storage, nor is it inventoried or counted similar to other potential drugs of abuse found in most operating rooms. Ease of access has been shown to be a factor in the incidence of propofol abuse. Most concerning is the high rate of accidental fatal outcomes reported in individuals who abuse propofol. The Peer Assistance Advisors of the AANA urgently recommend that all institutions, anesthesia departments, out-patient surgery centers, office anesthesia locations, and each clinical setting in which propofol is administered, adopt and apply the inventory and control methods currently in use for Schedule III substances, despite the lack of scheduled status, to their handling of the drug propofol. Propofol has become the most widely used IV induction agent for general anesthesia (1) because of its attractive properties of quick recovery (2) and minimal side effects. (3) (4)As such, it is commonly...

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The Long-term Psychological Effects of Daily Sedative Interruption on Critically Ill Patients

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Critically ill patients often receive sedatives, which may delay liberation from mechanical ventilation and intensive care unit discharge. Daily interruption of sedatives alleviates these problems, but the impact of this practice on long-term psychological outcomes is unknown. We compared psychological outcomes of intensive care unit patients undergoing daily sedative interruption (intervention) with those without this protocol (control). Assessments using (1) the Revised Impact of Event Scale (evaluates signs of posttraumatic stress disorder [PTSD]), (2) the Medical Outcomes Study 36 item short-form health survey, (3) the State-Trait Anxiety Inventory, (4) the Beck Depression Inventory-2, (5) and the Psychosocial Adjustment to Illness score (overall quality of adjustment to current or residual effects of illness) were done by blinded observers. The intervention group had a better total Impact of Events score (11.2 vs. 27.3, p  0.02), a trend toward a lower incidence of PTSD (0% vs. 32%, p  0.06), and a trend toward a better total Psychosocial Adjustment to Illness score (46.8 vs. 54.3, p  0.08). We conclude that...

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Introduction to Forensic Pathology | Gross

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Forensic pathology is the subspecialty area of pathology that is specifically involved in the investigation of sudden, unexpected, and/or violent deaths. Thus, the practice of forensic pathology involves applying forensic scientific and pathological techniques to the investigation of lethal episodes. In a more general sense, forensic pathology can also be considered part of the somewhat larger discipline of forensic medicine that applies forensic sciences to medical issues.

The main role for most forensic pathologists is to perform medicolegal autopsies; however, the nature of the practice is very variable depending on jurisdictions. In certain countries, such as Australia, forensic pathologists will only perform autopsies at the direction of the State Coroner, who is a lawyer and a judicial officer. In some jurisdictions in the United States, such as certain county-based medical examiners systems and most coroner systems, the official, legally mandated responsibility for the...

Additional Resource: Introduction to Forensic Pathology

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Melanie McGuire Trial

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McGuire, now 44, was convicted on April 23, 2007, of murder, possession of a weapon for unlawful purpose, desecration of of human remains and perjury in connection with the death of her husband, whose body parts were recovered from a set of matching black and green Kenneth Cole "Reaction" suitcases pulled from Chesapeake Bay near Virginia Beach in May 5, 2004, just days after he had allegedly gone missing from the couple's Woodbridge home. Days earlier, the couple had purchased a $500,000 home in Warren County.

William McGuire died from two gunshots wounds — one to the head and one to the chest. Melanie McGuire was charged with his murder in June 2005, more than a year after her husband's remains had been found.

Following a televised trial and conviction, she was sentenced to life in prison and must serve 85 percent before becoming eligible for parole.

McGuire sought post-conviction relief in 2014, claiming in court papers that she was denied effective representation by famed attorney Joseph Tacopina.

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Eyewitness Evidence A Guide for Law Enforcement

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The legal system always has relied on the testimony of eyewitnesses, nowhere more than in criminal cases. Although the evidence eyewitnesses provide can be tremendously helpful in developing leads, identifying criminals, and exonerating the innocent, this evidence is not infallible. Even honest and well-meaning witnesses can make errors, such as identifying the wrong person or failing to identify the perpetrator of a crime. To their credit, the legal system and law enforcement agencies have not overlooked this problem. Numerous courts and rule making bodies have, at various times, designed and instituted special procedures to guard against eyewitness mistakes. Most State and local law enforcement agencies have established their own policies, practices, and training protocols with regard to the collection and handling of eyewitness evidence, many of which are quite good.

In the past, these procedures have not integrated the growing body of psychological knowledge regarding eyewitness evidence with the practical demands of day-to-day law enforcement. In an effort to bring together the perspectives...

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Intelligence Community’s use of Mind-Control and Thought- Manipulation

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The preceding briefing is to educate the reader on the Intelligence Community’s use of Mind-Control and Thought- Manipulation that may be implemented today, as well as a few actual case scenarios of successful operations conducted by the Central Intelligence Agency, The Office of Naval Intelligence, and, in some limited capacity, Intelligence Support Activities units.

The senarios described in this briefing have been selected for their recognition factor for members of intelligence teams as “well known” events in recent history and for their direct involvements with various U.S. Intelligence agencies and selected operations connected to these events.

These manipulations and degrees of control are easily achieved after years of intensive research by both the CIA and the Office of Naval Intelligence. The methods cover the range of actual hypno-programming, through either overt or covert methods as utilized by the agency concerned in the use of R.H.I.C., U.S.I.C. , E.E.O.M. and E.D.O.M. techniques.

Ultrasound technology is most frequently used by the lesser intelligence agencies in their various

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Woman Savagely Stabbed, Raped

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File:# 72-12184

DEPARTMENT OF CHIEF MEDICAL EXAMINER-CORONER

Date: November 16,1972    Time: 1000 Hours

I performed an autopsy on the body of KATHLEEN LA CHANCE
at Office of Chief Medical Examiner-Coroner, 1104 N. Mission Rd.,
Los Angeles and from the anatomic findings and pertinent history I ascribe the death to:

MASSIVE HEMORRHAGE

DUE TO:   MULTIPLE STAB WOUNDS OF CHEST
FINAL: November 16, 1972

ANATOMICAL SUMMARY

           1. Multiple stab wounds
DESCRIPTION OF STAB WOUNDS AND INJURIES

Note:    For the purpose of identification the wounds are labeled numerically, however, this does not imply the order in which the wounds were inflicted. The descriptions that follow are made using the anatomic

There appears to be twelve stab wounds, ten located in the back within an area 12 inches and 19 ½ inches from the top of the head and 3 ½ inches to the left of the midline of the back and 3 ½ inches to the right of the midline of the back. Two additional stab wounds are...

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Infowar and Disinformation: From the Pentagon to the Net

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In 1967, a satire was published under the title “Report From Iron Mountain on the Possibility and Desirability of Peace.” This analysis soberly reflected, in think-tank style, on the importance to society of waging war. Leonard Lewin, who pretended that the secret report was leaked and did not claim authorship until five years later, argued forcefully that war provides a type of social and psychological glue, without which society cannot function.

“Roughly speaking,” Lewin writes, “the presumed power of the 'enemy' sufficient to warrant an individual sense of allegiance to a society must be proportionate to the size and complexity of the society. Today, of course, that power must be one of unprecedented magnitude and frightfulness.”[1] Lewin's tongue-in- cheek premise is that before peace breaks out, it becomes urgent to find substitutes for war.

They say that life imitates art. Almost 30 years later, Lewin's claim of authorship is lost amid the general enthusiasm over the manuscript. Dog-eared copies of “Report from Iron Mountain”

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Indoctrination in Psychotherapy and Psychoanalysis:

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Indoctrination in Psychotherapy and Psychoanalysis:

The Double Whammy, Interrogation and Other Methods of Covert Control

Theodore L. Dorpat

In treatment, the psychotherapist is in a position of power. Often, this power is unintentionally abused. While trying to embody a compassionate concern for patients, therapists use accepted techniques that can inadvertently lead to control, indoctrination, and therapeutic failure. Contrary to the stated tradition and values of psychotherapy, they subtly coerce patients rather than respect and genuinely help them. The more gross kinds of patient abuse, deliberate ones such as sexual and financial exploitation, are expressly forbidden by professional organizations. However, there are no regulations discouraging the more covert forms of manipulation, which are not even considered exploitative by many clinicians. In this book, noted psychiatrist Theo. L. Dorpat strongly disagrees. Using a contemporary interactional perspective Dorpat demonstrates the destructive potential of manipulation and indoctrination in treatment.

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