Transgender Juveniles Transgender juveniles shall be treated pursuant to this policy muscle relaxant depression quality imuran 50 mg, and afforded the same privileges and protections as other juveniles under local muscle relaxant ointment order 50mg imuran otc, state or federal law muscle relaxant johnny english order imuran 50mg amex. If officers determine that the safety of a transgender prisoner or other prisoner would be compromised by transporting the transgender prisoner in the same vehicle as other prisoners spasms 1983 download cheap imuran 50mg on-line, transgender prisoners may be transported in a separate vehicle muscle relaxant exercises buy imuran 50 mg low cost. Complaints Prisoner Processing in Temporary Holding Area Transgender prisoners held in a temporary holding area shall be separated from nontransgender prisoners by sight and sound when possible spasms treatment cheap imuran 50mg visa. If this is not possible muscle relaxant metaxalone side effects generic 50 mg imuran fast delivery, a supervisor shall respond to determine the best solution spasms while peeing discount imuran 50mg mastercard. The use of reasonable physical force by officers is authorized in situations that cannot be otherwise controlled. Any time an officer uses force, they shall ensure that appropriate medical treatment or first aid is provided to the subject of the force without unnecessary delay. Officers are involved on a daily basis in numerous and varied encounters with people, and when warranted to do so, may use force in carrying out their duties. It is the policy of the Department that each incident involving the application of any degree of physical force upon the person of another must be evaluated based on the facts known to the officer at the time of the incident. The totality of the circumstances will be considered when reviewing use of force incidents. Under no circumstances may the use of physical force be more than that which is necessary to achieve a lawful purpose. Officers are permitted to use only the amount of force that is objectively reasonable and necessary to protect themselves or others from what is reasonably believed to be a threat of death or bodily harm, to effectuate an arrest, or gain compliance with a lawful order. Whether the use of force is reasonable shall be judged from the perspective of an officer at the time of the incident, based upon facts known or reasonably available to him or her. Every member of the Police Department shall refrain from using force unnecessarily and shall prevent similar conduct by others. The use of excessive force will subject officers to discipline, possible criminal prosecution, or civil liability. Use of Force Continuum Overview Soft Personal Weapons: Strike applied to a nerve motor point as a stunning or distraction technique to cause a motor dysfunction and balance displacement in order to control a resistant subject (an open hand strike or knee strike to a nerve motor point) the Use of Force Continuum is designed to provide an overview and visual representation of the force options available to officers. It is a fluid instrument, which attempts to depict the dynamics of a confrontation. The continuum is only a guide and cannot take into consideration every possible situation that an officer may face. Methods of tactical disengagement include, but are not limited to: Area containment Surveillance Waiting out a subject Summoning reinforcements Requesting specialized units It is important to note that an officer does not need to use the lowest level of force on the continuum when the officer can articulate that a higher level of force was reasonable. An officer may use force at any level on the continuum, provided that the force selected is objectively reasonable. Engagement of Tactical Options Whenever possible, officers should use communication skills to attempt to control situations. Verbal communication is essential throughout the arrest process to deescalate the situation. Distance gives an officer more time to evaluate and react appropriately to a threat. An officer should continually reassess their options throughout an incident and take into account that highrisk incidents are fluid and continually changing. An officer should consider using cover and concealment when it is available and movement (dynamic cover) when it is not. Whenever possible, subjects should be allowed to submit to arrest before force is used. Lethal Force Officers may only use lethal force when they have an objectively reasonable belief that the suspect poses an imminent threat of death or serious physical injury to the officer or to another person. A decision to use lethal force can only be justified by facts known to the officer at the time the decision is made. Facts unknown to the officer, no matter how compelling, cannot be considered in subsequent investigations, reviews, or hearings. Officers must avoid placing themselves in situations where vehicles may strike them. Firearms may be used to destroy seriously injured animals or those posing an imminent threat to human safety. Officers shall also notify a Supervisor upon receipt of an allegation of excessive force. Supervisors shall conduct a review of each use of force incident when: An individual is handcuffed for officer safety and released An officer points a weapon at an individual An officer employs an unresisted escort An officer utilizes the Hobble strap without the use of force Handcuff and release incidents shall be documented in a Case Record that details the circumstances of the incident. These reports will be reviewed and signed by a Shift Commander or Acting Shift Commander. A Use of Force Review is not required when: A full custody arrest is made without the use of force and transport occurs, but the subject is released without being charged, i. Under this circumstance, a Supervisor of equal rank or above will be responsible for completing the review. Supervisors involved in use of force incidents shall not sign and approve their own Use of Force Reports. While conducting the Use of Force Review, the Supervisor shall critically evaluate all information obtained. The Supervisor shall cease questioning of the possible respondent officer(s), but complete the Use of Force Review. Based on the review, the Supervisor shall conclude whether or not the use of force was justified and within Departmental policy. This conclusion shall be based on the totality of the circumstances, Departmental policy, and training. Statements obtained from all civilian witnesses, when feasible the identity of all officers who were involved in the incident or were on the scene when it occurred All reports which indicate whether an injury occurred, whether medical care was provided, and whether the subject refused medical treatment Photographs or videotapes taken of the incident or of injuries, before and after cleaning and treatment Any other relevant documents or observations Supervisors shall ensure that all of the required information is included on the Use of Force Review Report. Any reviewing member within the chain of command may attach comments, direct that additional evidence be gathered, or recommend that a formal investigation be conducted. Additional comments may be added to the Use of Force Review Report but no further action is required. The command officer must document the specific facts or circumstances that form the basis for their decision on the Use of Force Review Report. The law, directive, or other governing policy either violated or not violated must be cited, and the actions at issue described. During their review, the District/ Division Commander/Manager shall evaluate the Use of Force Reviews conducted by the Supervisor, identifying any deficiencies in the review. Any discrepancies noted shall be documented in writing by the District/Division Commander/Manager on the Use of Force Review Report. Supervisors shall be responsible for correcting any deficiencies identified by the District/Division Commander/Manager. District/Division Commanders/Managers shall hold Supervisors accountable for the quality of their reviews. They shall ensure that appropriate disciplinary or corrective action is taken when a Supervisor fails to: Conduct a timely and thorough review Recommend appropriate corrective action Implement appropriate corrective action If the District/Division Commander/ Manager concurs with the findings of the Use of Force Review Report, they shall forward a copy to: District/Division Commander/Manager Review District/Division Commanders/Managers may extend the seven day time limit for Supervisors to complete their review due to extenuating circumstances. Serious incidents include those resulting in: Death, or the likelihood of death Hospitalization A broken bone Loss of consciousness Serious disfigurement Disability All incidents where a person receives a bite from a Departmental canine Firearms discharges directed at a person All Critical Firearm Discharges Striking a handcuffed individual (but not simply handcuffing) 7. The panel shall conduct an analysis of all uses of force by members of the Department on a quarterly basis, and forward the results of the analysis to the Chief of Police. This analysis shall be submitted to the Chief of Police by February 1st of the following calendar year. The panel shall prepare a written report with their findings and recommendations to the Chief of Police. This report shall become a part of the official investigative file for the incident. The report shall include a description of the incident including all uses of force. It will also include a summary of all evidence that supports their findings, and an analysis that supports those findings. Animals Where an officer discharges a firearm for the purpose of humanely destroying an injured animal, no Use of Force Review shall be conducted. The involved officer shall complete a Case Record, and a Use of Force Review Report (the Discharge of Firearms portion). If an officer destroys an animal for any other purpose, a Use of Force Review shall be conducted. Garner During civil disturbances and barricades, force that is used at the direction of the onscene commander shall be documented on a single Use of Force Review Report. The Supervisor or ranking officer present when force is used shall be responsible for completing the report. Officers who independently use force while involved in a civil disturbance incident or a barricade without the authorization of the on-scene commander shall, at minimum, complete a Case Record. Supreme Court determined the standard to be used to judge constitutional claims of excessive force brought by citizens against police officers. Facts of the Case On November 12, 1984, Graham, a diabetic, asked Berry, a friend, to drive him to a convenience store to purchase orange juice to prevent the onset of an insulin reaction. Connor, a city police officer, became suspicious after seeing Graham hastily enter and leave the store. Backup officers arrived on the scene, handcuffed Graham, ignoring attempts to explain and treat his condition. Graham filed suit against all the officers involved, alleging the use of excessive force in making the investigatory stop. Supreme Court, the "reasonableness" of a particular use of force must be judged from the perspective of a reasonable officer on the scene, rather than with the benefit of hindsight. Thus, the test used by the District Court is incompatible with a proper analysis under the Fourth Amendment. The test of "reasonableness" under the Fourth Amendment cannot be precisely defined. However, its proper application requires careful attention to the facts and circumstances of each particular case, including the severity of the crime, whether the suspect posed an immediate threat to officers or citizens, and whether the suspect actively resisted arrest or attempted to flee. The need for the application of force the relationship between the need and the amount of force that was used the extent of the injury inflicted Whether the force was applied in a good faith effort to maintain and restore discipline, or maliciously and sadistically for the purpose of causing harm Using the above factors, the District Court found that the amount of force used was appropriate under the circumstances. The Court affirmed the Court of Appeals decision limiting the use of deadly force to apprehend a fleeing felon. Facts of the Case On October 3, 1974, a Memphis, Tennessee police officer and his partner were dispatched to a call for a prowler inside a residence. Upon arriving on the scene, a neighbor advised that someone was breaking in to the house next door. As his partner radioed for assistance, the officer went to the back of the house where he heard the door slam and saw someone running across the backyard. He saw no signs of a weapon, and though not certain, was "reasonably sure" that the suspect was unarmed. While the suspect was crouched at the base of the fence, the officer ordered him to stop. When the officer took a few steps toward the suspect, he started climbing the fence. The officer was convinced that the suspect would elude capture if he got over the fence, so the officer shot the suspect. In using deadly force to prevent escape, the officer was acting under the authority of a Tennessee statute and following department policy. It held that the killing of a fleeing suspect is a "seizure" under the Fourth Amendment, and the use of deadly force to prevent escape of all felony suspects, whatever the circumstances, is constitutionally unreasonable. The Tennessee statute did not adequately limit the use of deadly force because it failed to distinguish between felonies of different magnitudes. This balancing process stipulates that, even though there is probable cause to seize a suspect, an officer may not always do so by killing him. The Court further held that the fact that an unarmed suspect burglarized a dwelling at night does not automatically mean he is dangerous. The Supreme Court affirmed the decision of the Court of Appeals on March 27, 1985. If this is impossible due to impassable road conditions or severe inclement weather, civilian employees shall report to the nearest County Police facility, where arrangements can be made to transport them to their assigned work site. If employees cannot respond to the nearest County Police facility, they shall contact their Supervisor for further instruction. Emergency notification procedures for the call-out of off-duty personnel Deployment of personnel during a Signal 26 Shopping centers and other businesses susceptible to looting Shopping malls maintaining private security on a 24-hour basis where officers could seek shelter Police and Fire Department facilities within their District that could be used to house officers for sleeping purposes Procedures to ensure that vehicles parked at police facilities are moved before snow removal 1. They shall report to work as scheduled during weather-related emergencies unless otherwise directed by their Supervisor. Officers shall continue to respond to emergency calls for service during a Signal 26. The County will not tolerate violence in the workplace and is committed to maintaining an environment free of all forms of violence, threats of violence, and all forms of intimidation and criminal harassment. Supervisors shall ensure that all workplace disturbances are properly investigated and documented. Most respondents agreed that "the question was easy for me to answer" and that "I would answer this question on a registration form at this health center. Sugar Nutritionally identical Sweets are clearly fattening if taken in excess Multiple studies show no difference in fattening between different sugars Consensus by Am. Fat storage set point Animal overfeeding / underfeeding studies Weight gain leads to increased metabolic rate/spontaneous physical activity Mismatch of only 2% only 22 calories/day 0. Jaw wiring does not lead to weight loss, hunger persists, patients bypass blockage Malabsorption Cancer risks: 5% after bariatric surgery, 8% without Most significant in women Confirmed in 16,000 pt. Why: Early detection and intervention can help infants stay on track with speech, language, and communication skills. Association between opioid prescribing patterns and opioid overdose-related deaths. Comparative effectiveness of exercise, acupuncture, and spinal manipulation for low back pain. Effectiveness of an 8-week exercise programme on pain and specificity of neck muscle activity in patients with chronic neck pain: a randomized controlled study. Addictionrelated assessment tools and pain management: instruments for screening, treatment planning and monitoring compliance. For patients currently on opioids see Consideration of Continuing Opioid Treatment for Pain algorithm. For each recommendation, the relevant resource used to support that recommendation is noted. Providers should consider checking the Prescription Monitoring Program for patients presenting with pain if his or her opioid exposure is uncertain. Prescribe ibuprofen and acetaminophen combination as first-line treatment for dental pain. The referring medical clinician for acute dental pain should not routinely prescribe opioid medications. Han, 2015 (Observational Study); Hooten, 2015 (Observational Study); Jones, 2013a (Observational Study); Juurlink, 2012 (Review); Sehgal, 2012 (Review); Bohnert, 2011 (Observational Study); Liebschutz, 2010 (Observational Study); Chou, 2009c (Evidence Review); Martell, 2007 (Systematic Review) Hooten, 2016 (Summary Article); Janssens, 2015 (Observational Study); Asmundson, 2009 (Report) Institute for Clinical Systems Improvement Psychotherapy such as cognitivebehavioral therapy or mindfulnessbased stress reduction is recommended for patients with a chronic pain diagnosis. Relevant References International Association for the Study of Pain, 2014 (Guideline); Gatchel, 2006 (Review) 8 Treatment: psychotherapy strategies 10 Treatment: physical rehabilitation modalities Exercise should be a component of the treatment for a patient with chronic pain. International Association for the Study of Pain, 2014 (Guideline); Kamper, 2014 (Systematic Review); Castro, 2012; (Randomized Control Trial); Grossman, 2007 (Textbook); Gillis, 2006 (Randomized Control Trial); Turner, 2006 (Randomized Control Trial); Broderick, 2005 (Randomized Control Trial); Smyth, 2003 (Review) Falla, 2013 (Randomized Control Trial); Cuesta-Vargas, 2011 (Randomized Control Trial); Standaert, 2011 (Systematic Review); Dufour, 2010 (Randomized Control Trial); Hall, 2008 Systematic Review/Meta-analysis); Hurwitz, 2008 Evidence Synthesis); Hayden, 2005 (Systematic Review) Vincent, 2013 (Systematic Review); Standaert, 2011 (Systematic Review) 10 Treatment: passive physical modalities Treatment: active physical modalities 10 Passive modalities should only be performed as an adjunct to a concomitant active physical therapy or exercise program. Extending physical therapy beyond 12 weeks for chronic pain patients should be based on objective clinical improvement. Cuesta-Vargas, 2015 (Randomized Control Trial); Cramer, 2013 (Randomized Control Trial); Falla, 2013 (Randomized Control Trial); Standaert, 2011 (Systematic Review); Dundar, 2009 (Randomized Control Trial); Koumantakis, 2005 (Randomized Control Trial); Rainville, 2002 (Observational Study) Relevant References American Geriatric Society 2015 Beers Criteria Update Expert Panel, 2015 (Guideline); Gray, 2015 (Observational Study); Petrov, 2014 (Observational Study); Chou, 2007 (Guideline); Richards, 2012 (Systematic Review); Liu, 2010 (Observational Study); van Tulder, 2003 (Systematic Review) Volkow, 2016b (Summary Article); Wasan, 2015 (Observational Study); Argoff, 2014 (systematic review); Jones, 2014 (Observational Study); Atluri, 2012 (Review); Jones, 2012 (Observational Study); Moore, 2009 (Observational Study) 13. If impairment or risk is detected in a geriatric patient, initiation of opioids should be at half the usual dose. An individualized approach that weighs the risks and benefits of driving and other activities should be taken with patients chronically on stable opioids who have tolerance and do not show evidence of sedation. Long-acting opioids should be reserved for patients with established opioid tolerance and in whom the prescriber is confident of medication adherence. Relevant References Centers for Disease Control and Prevention, 2016 (Guideline); Hooten, 2015 (Observational Study); Noble, 2010 (Systematic Review/meta-analysis); Starrels, 2010 (Systematic Review); Arnold, 2006 (Review) 13. The first opioid prescription for acute pain should be no more than 20 low-dose, short-acting opioids or three days of medication, whichever is less. Chou, 2015 (Systematic Review); Chaparro, 2014 (Systematic Review/Metaanalysis); Manchikanti, 2006 (Observational Study) Opioids should be avoided for patients with substance use disorder or concomitant benzodiazepines use.
The role of sacred prostitution is similar: both to unleash and to channel the powers of fertility 3m muscle relaxant order 50 mg imuran amex. Even today spasms coughing discount imuran 50mg amex, popular holidays areexemplifiedbyoutbreaksoferoticism;womanisnotjustanobject ofpleasurebutameansofreachingthishubrisinwhichtheindividual surpasses himself muscle relaxant vecuronium discount imuran 50mg without prescription. He finds the mysterious alchemies of life repugnant spasms kidney area generic 50 mg imuran free shipping, while his own life is nourished and enchanted by the tasty fruits of the earth; he desires to appropriate them for himself; he covets Venus freshly emergingfromthewaters muscle relaxant menstrual cramps purchase 50mg imuran with mastercard. He wantstoconquer spasms movie order imuran 50 mg on line,take spasms spanish cheap imuran 50mg on-line,andpossess;tohaveawomanistoconquer her;hepenetratesherastheplowshareinthefurrows;hemakesher hisashemakeshistheearthheisworking:heplows back spasms 20 weeks pregnant cheap 50 mg imuran free shipping,heplants,he sows: these images are as old as writing; from antiquity to today a thousand examples can be mentioned. Dependingonwhethermanfeelscrushedby the powers encircling him or arrogantly believes he is able to make themhis,herefusesordemandsthathiswifebedeliveredtohimasa virgin. MarcoPoloassertedthatfortheTibetans, "none of them wanted to take a virgin girl as wife. Al-Bakri,the Arabgeographer,speakingoftheSlavicpeoples,notesthat"ifaman getsmarriedandfindsthathiswifeisavirgin,hesays:`Ifyouwere worthsomething,menwouldhavelovedyouandoneofthemwould have taken your virginity. Theseimagesexpress the idea that the feminine principle is so powerful and threatening becauseitisintact. Sometimes, the mother, older sister, or some other matronsystematicallydeflowersthegirlandthroughoutherchildhood widens the vaginal opening. Deflowering can also be carried out by womenduringpubertyusingastick,abone,orastone,andthisisnot consideredasurgicaloperation. Allholyobjectsareknowntobedangerous fortheoutsider,butconsecratedindividualscanhandlethemwithout risk;thatexplainswhypriestsandchiefsareabletotamethemalefic forces against which the spouse has to protect himself. Thehusbanddefendshimselfinyetanother way: he himself deflowers the virgin but during ceremonies that renderhiminvulnerableatthiscriticaljuncture;forexample,hedoesit infrontofthewholevillagewithastickorbone. There is also the case of the man allowed to deflowerhiswifenormallybuthehastowaitthreedaystoejaculate inhersothatthegeneratingseedisnotsoiledbyhymenblood. Man took the ardor of the wild horseandtheviolenceoflightningandwaterfallsastheinstruments ofhisprosperity. First of all, the idea of possession is always impossible to realize positively; the truth is that one never has anythingoranyone;oneattemptstoaccomplishitinanegativeway; thesurestwaytoassertthatagoodismineistopreventanotherfrom using it. And then nothing seems as desirable to man as what has never belonged to any other human: thus conquest is a unique and absoluteevent. Virginlandhasalwaysfascinatedexplorers;alpinists kill themselves every year attempting to assault an untouched mountainoreventryingtoopenupanewtrail;andthecuriousrisk theirlivestodescendundergroundtothebottomofunprobedcaves. Anobjectthatmenhavealreadymasteredhasbecomeatool;cutoff from its naturalbonds, it loses its deepest attributes; there is more promiseinthewildwateroftorrentsthaninthatofpublicfountains. Avirginbodyhasthefreshnessofsecretsprings,themorningbloom of a closed corolla, the orient of the pearl the sun has never yet caressed. Cave,temple,sanctuary,orsecretgarden:likethechild,man is fascinated by these shadowy and closed places never yet touched byanimatingconsciousness,waitingtobelentasoul;itseemstohim thatheinfactcreatedwhatheistheonlyonetograspandpenetrate. Moreover, every desire pursues the aim of consuming the desired object, entailing its destruction. By breaking the hymen, man possesses the feminine body more intimately than by a penetration that leaves it intact; in this irreversible operation, he unequivocally makes it a passive object, asserting his hold on it. This exactly 208 expressesthemeaninginthelegendoftheknightwhohackshisway through thorny bushes to pick a rose never before inhaled; not only doesheuncoverit,buthebreaksitsstem,therebyconqueringit. The curseisintheirveryflesh,thisfleshthatisobjectfornosubject,that no desire has made desirable, that has bloomed and wilted without findingaplaceintheworldofmen;turnedawayfromherdestination, the old maid becomes an eccentric object, as troubling as the incommunicable thinking of a madman. If feminine virginity has not been consecrated to a god, it is easilythenthoughttoimplymarriagewiththedevil. Exorcised by deflowering rites or on the contrary purified by her virginity,thewifecouldthusbedesirableprey. Sheisallthefauna,all the earthly flora: gazelle, doe, lilies and roses, downy peaches, fragrant raspberries; she is precious stones, mother-of-pearl, agate, pearls, silk, the blue of thesky, the freshness of springs, air, flame, earth,andwater. Hereagain,throughout antiquity, the Middle Ages, and the modern period, it would be necessary to quote a thick anthology. Nymphs, dryads, mermaids, water sprites, and fairies haunt the countryside, the woods, lakes, seas, and moors. For the sailor, the sea is a dangerous woman, perfidious and difficult to conquerbutthathecherishesbydintoftamingit. Proud,rebellious, virginal,andwicked,themountainiswomanforthemountainclimber who wants to take it, even at risk of life. It is often said that these comparisons manifest sexual sublimation; rather, they express an affinitybetweenwomanandtheelementsasprimalassexualityitself. InhisnovelToaGod Unknown, Steinbeck shows a man who chooses a mossy rock as mediator between him and nature; inThe Cat, Colette describes a younghusbandwhosettleshisloveonhisfavoritefemalecatbecause this gentle wild animal enables him tohave a grasp on the sensual universe that his woman companion cannot give. The Other can be embodiedintheseaandthemountainjustaswellasinthewoman; they provide man with the same passive and unexpected resistance thatallowshimtoaccomplishhimself;theyarearefusaltoconquer,a 210 preytopossess. She must embody the wondrous blossoming of life while concealing its mysterious disturbancesatthesametime. The ideal of feminine beauty is variable;butsomerequirementsremainconstant;oneofthemisthat sincewomanisdestinedtobepossessed,herbodyhastoprovidethe inert and passive qualities of an object. The only symmetry to be found in the feminine ideal is in Sparta, Fascist Italy, and Nazi Germany, societies that destined woman for the state and not for the individual and that consideredherexclusivelyasmother,withnoplaceforeroticism. Herbodyisgraspednotas the emanation of a subjectivity but as a thing weighted in its immanence;thisbodymustnotradiatetotherestoftheworld,itmust notpromiseanythingbutitself:itsdesirehastobestopped. Themost naive form of this requirement is the Hottentot ideal of the steatopygousVenus,asthebuttocksarethepartofthebodywiththe fewest nerve endings, where the flesh appears as a given without purpose. The taste of people from the East for fleshy women is similar; they love the absurd luxury of this fatty proliferation that is not enlivened by any project, that has no other meaning than to be there. Weighteddownby fatoronthecontrarysodiaphanousthatanyeffortisforbiddentoit, paralyzed by uncomfortable clothes and rites of propriety, the body thusappearedtomanashisthing. Anequivocalidol:manwantedhererotic, forherbeautytobepartofthatofflowersandfruits;butshealsohad to be smooth, hard, eternal like a stone. The role of dress is both to linkthebodymorecloselytoandtowrestitawayfromnature,togive a necessarily set artifice to palpitating life. Woman was turned into plant,panther,diamond,ormother-of-pearlbyminglingflowers,furs, precious stones, shells, and feathers on her body; she perfumed herselfsoastosmellofrosesandlilies:butfeathers,silk,pearls,and perfumesalsoworkedtohidetheanimalrawnessfromitsfleshand odor. Womanwasevenmoredesirablewhennaturewasshownoff to full advantage and more rigorously subjugated: the sophisticated woman has always been the ideal erotic object. Inprimitivepeople,thisideaistheperfectionof the popular type: a thick-lipped race with a flat nose forged a thicklipped Venus with a flat nose; later, the canons of a more complex 212 aestheticswouldbeappliedtowomen. Butinanycase,themorethe traits and proportions of a woman seemed contrived, the more she delighted the heart of man because she seemed to escape the metamorphosis of natural things. The result is this strange paradox that by desiring to grasp nature, but transfigured, in woman, man destineshertoartifice. Sheisnotonlyphysisbutjustasmuchantiphysis; and not only in the civilization of electric permanents, hair waxing, latex girdles, but also in the country of African lip-disk women, in China, and everywhere on earth. However, here is the first lie, the first betrayal of woman: of life itself, which, even clothed in the most attractive forms, is still inhabited by the ferments of old age and death. The very use man makesofherdestroyshermostpreciousqualities;weigheddownby childbirth,sheloseshersexualattraction;evensterile,thepassageof time is enough to alter her charms. Old and ugly women not only are objects without assets but also provoke hatredmixedwithfear. Demeter survives in Venus emerging from the waters, fresh foam, the blond harvest; appropriating woman for himself through the pleasure he derives 213 fromher,manawakensinherthesuspiciouspowersoffertility;itis the same organ he penetrates that produces the child. Malinowski is surprised that young people who sleep together freely in the "house of the unmarried"showofftheirlovelivessoreadily;theexplanationisthat an unmarried daughter is considered unable to bear a child and the sexual act is merely a quiet and ordinary pleasure. On the contrary, oncemarried,herspousecannotgiveheranypublicsignofaffection, nor touch her, and any allusion to their intimate relations is sacrilegious; she then has to be part of the formidable essence of mother, and coitus becomes a sacred act. Ithas been wondered if the horror man feels for woman comes from that inspired by sexuality in general, or vice versa. We have seen that in Leviticus,inparticular,wetdreamsareconsideredastaineventhough woman has nothing to do with them. And in our modern societies, masturbation is considered a danger and a sin; many children and young boys whoindulge in it suffer terrible anxieties because of it. He discovers woman in discovering his own sex, even if she is not given to him in flesh and blood, nor in image;andinversely,womanisfearsomeinasmuchassheembodies sexuality. Theimmanentandtranscendentaspectsoflivingexperience canneverbeseparated:whatIfearordesireisalwaysanavatarofmy own existence, but nothing comes to me except through what is not myself. Thenonselfisinvolvedinwetdreams,inerection,andifnot in the precise figure of woman, at least in Nature and Life: the individual feels possessed by a foreign magic. Likewise, his ambivalencetowardwomenisseeninhisattitudetowardhisownsex organ; he is proud, he laughs about it, he is embarrassed by it. The adultmanlooksuponhissexorganasasymboloftranscendenceand power; he is as proud of it as a muscle and at the same time as a magicalgrace:itisafreedomrichwiththewholecontingenceofthe given, a given freely desired; this is the contradictory aspect that enchantshim;buthesuspectsthetrapinit;thissexorganbywhich he claims to assert himself does not obey him; full of unassuaged desires,arisingunexpectedly,sometimesrelievingitselfindreams,it manifests a suspicious and capricious vitality. Man claims to make Spirit triumph over Life, activity over passivity; his consciousness keepsnatureatadistance,hiswillshapesit,butinthefigureofhis sex organ he rediscovers life, nature, and passivity in himself. Whathecalledwillisattachmenttolife, whichissufferinganddeath,whilethebrainisthoughtthatseparates itselffromlifewhilerepresentingit:sexualshameaccordingtohimis what we feel about our stupid carnal stubbornness. The sex organ of others draws laughter easily; but because the erection looks like a plannedmovementandyetisundergone,itoftenlooksridiculous;and thesimplementionofgenitalorgansprovokesglee. Malinowskisays that for the wild people among whom he lived, just mentioning the word for these "shameful parts" made them laugh uncontrollably; manycrudeorsaucyjokesarenotmuchmorethanrudimentarypuns onthesewords. Forsomeprimitivepeoples,duringthedaysdevoted to weeding out gardens, women had the right to brutally rape any strangerthatdaredtocomeintothevillage;attackinghimalltogether, theyoftenlefthimhalf-dead:thetribesmenlaughedatthisexploit;by thisrape,the victim was constituted as passive and dependent flesh; hewaspossessedbythewomenandthroughthembytheirhusbands, whileinnormalcoitusmanwantstoaffirmhimselfaspossessor. But this is where he will experience the ambiguity of his carnal conditionmostobviously. Onlyabodycantouchanotherbody;the malemastersthedesiredfleshonlybybecomingfleshhimself;Eveis given toAdam for him to accomplish his transcendence in her, and she draws him into the night of immanence; the mother forges the obscure wrapping for her son from which he now wants to escape, while the mistress encloses him in this opaque clay through the vertigoofpleasure. Odor, damp, fatigue, boredom: a whole literature describes this dreary passion of a consciousness become flesh. Desire often contains an element of disgust and returns to disgust when it is assuaged. Soonhisdesireisreborn;andoftenit is the desire not only for woman in general but for this specific woman. Becauseinhisown bodymandoesnotfeelthesexualneedexceptasageneralonesimilar tohungerorthirstwithoutaparticularobject,thebondthatlinkshim to this specific feminine body is forged by the Other. The link is mysterious like the foul and fertile womb of his roots, a sort of passive force: it is magic. The hackneyed vocabulary of serialized novelswherethewomanisdescribedasanenchantressoramermaid who fascinates man and bewitches him reflects the oldest and most universalofmyths. Magic,saidAlain,is thespiritlurkinginthings;anactionismagicwhenitemanatesfroma passivity instead of being produced by an agent; men have always considered woman precisely as the immanence of the given; if she produces harvests and children, it is not because she wills it; she is not subject, transcendence, or creative power, but an object charged withfluids. Insocietieswheremanworshipssuchmysteries,woman, becauseofthesequalities,isassociatedwithreligionandveneratedas a priestess; but when he struggles to make society triumph over 217 nature,reasonoverlife,willoverinertfact,womanisregardedasa sorceress. Butwoman is not fully integrated into the world of men; as other, she counters them; it is natural for her to use the strengths she possesses, not to spread the hold of transcendence across the community of men and into the future, but, being separate and opposed, to draw males into thesolitudeofseparation,intothedarknessofimmanence. Sheisthe mermaidwhose songs dashed the sailors against the rocks; she is Circe, who turned her lovers into animals, the water sprite that attractedthefishermantothedepthsofthepools. Themancaptivated by her spell loses his will, his project, his future; he is no longer a citizen but flesh, slave to his desires, he is crossed out of the community,enclosedintheinstant,thrownpassivelyfromtortureto pleasure;theperversemagicianpitspassionagainstduty,thepresent against the unity of time, she keeps the traveler far from home, she spreads forgetfulness. In attempting to appropriate the Other, man mustremainhimself;butwiththefailureofimpossiblepossession,he triestobecomethisotherwithwhomhefailstounite;sohealienates himself, he loses himself, he drinks the potion that turns him into a strangertohimself,hefallstothebottomofdeadlyandroilingwaters. The Mother dooms her son to death in giving him life; the woman loverdrawsherloverintorelinquishinglifeandgivinghimselfupto thesupremesleep. Born of flesh, man accomplishes himself in love as flesh, and flesh is destinedtothegrave. ThealliancebetweenWomanandDeathisthus confirmed; the great reaper is the inverted figure of corn-growing fertility. But it is also the frightening wife whose skeleton appears underdeceitfulandtenderflesh. Fromthe day of birth, man begins to die: this is the truth that the mother embodies. Shouldhetryto differentiate them, he still finds in both one fact alone, that of his carnalcondition. Hewasatlastnearing the end of an interminable voyage that had been pursued since thebeginning of the world. Little by little he dissolved into an immensity that cradled him round without shape or end. All women were confused into one giant land, folded upon him, suaveasdesireburninginsummer. He, meanwhile, recognised with a fearful admiration the power that is enclosed within woman, the long, stretched, satin thighs, the knees like two ivory hills. When he traced the polished arch of the back, from the waist to the shoulders, he seemed to be feeling the vault that supports the world. Then he was seized with a rage to pierce that delightful envelope,andatlastwintotheverysourceofallthisbeauty. The womannowonlylivedtobecleavedbytheshare,toopentohim her vitals, to gorge herself with the humours of the beloved. He,man,theisolated,theseparated,thecutoff,wasgoingto gush forth from out of his own substance, he, the first, would comeforthfromhisfleshlyprisonandatlastgofree,matterand soul,intotheuniversalmatrix. Tohimwasreservedtheunheard of happiness of overpassing the limits of the creature, of 219 dissolving into the one exaltation object and subject, question and answer, of annexing to being all that is not being, and of embracing, in an unextinguishable river, the empire of the unattainable. Buteachcomingandgoingofthebowawoke,intheprecious instrument it held at its mercy, vibrations more and more piercing. Suddenly, a last spasm unloosed him from the zenith, andcasthimdownagaintoearth,tothemire. Ifamandoesnotthinklifeis unique,ifheisnotconcernedwithhissingulardestiny,ifhedoesnot fear death, he will joyously accept his animality. Man can thus enjoy woman without worrying or having to defendhimselfagainsthimselforher. TheThousandandOneNights looks on her as a source of creamy delights much like fruits, jams, rich desserts, and perfumed oils. This sensual benevolence can be foundtodayamongmanyMediterraneanpeoples:replete,notseeking immortality, the man from the Midi grasps Nature in its luxurious aspect,relisheswomen;bytraditionhescornsthemsufficientlysoas not to grasp them as individuals: between the enjoyment of their bodies and that of sand and water there is not much difference for him;hedoesnotexperiencethehorroroftheflesheitherinthemorin himself. InConversations in Sicily, Vittorini recounts, with quiet amazement,havingdiscoveredthenakedbodyofwomanattheageof seven. Greek optimist philosophy went beyond PythagoreanManichaeism;theinferiorissubordinatetothesuperior and as such is useful to him: these harmonious ideologies show no hostilitywhatsoevertotheflesh. TurnedtowardtheheavenofIdeas orintowardtheCityorState,theindividualthinkinghimselfasnous orasacitizenthinkshehasovercomehisanimalcondition:whether he gives himself up to voluptuousness or practices asceticism, a woman firmly integrated into male society is only of secondary importance. Itistruethatrationalismhasnevertriumphedtotallyand erotic experience remains ambivalent in these civilizations: rites, mythologies, and literature are testimony to that. Christianity is what drapes woman anew with frightening prestige: one of the fears the rending of the unhappy consciousness takesformanisfearoftheothersex. Since woman never stopped being Other, of course, male and female are never reciprocally considered flesh: the flesh for the Christian male is the enemy Other and is not distinguished from woman. Thefirst ChurchFathers-Origen,Tertullian,andJerome-thoughtthatMary hadgivenbirthinbloodandfilthlikeotherwomen;buttheopinions of SaintAmbrose and SaintAugustine prevail. In puritan Anglo-Saxon countries in particular, womanstirsupmoreorlessavowedterrorinmostadolescentsand manymen. People also readily think that sexual intercoursemakesmanlosehismuscularstrengthandmentallucidity, consumes his phosphorus, and coarsens his sensitivity. The same dangers threaten in masturbation; and for moral reasons society considers it even more harmful than the normal sexual function. Woman is vampire,ghoul,eater,drinker;hersexorganfeedsgluttonouslyonthe 222 male sex organ. Some psychoanalysts have tried to give these imaginings scientific foundations: the pleasure woman derives from coitus is supposed to come from the fact that she symbolically castratesthemaleandappropriateshissexorgan. Butitwouldseem thatthesetheoriesthemselvesneedtobepsychoanalyzedandthatthe doctors who invented them have projected onto them ancestral terrors. In patriarchal societies, woman kept many of the disquieting virtues she held in primitive societies. That explains why she is never left to Nature, why she is surrounded by taboos,purifiedbyrites,andplacedunderthecontrolofpriests;man is taught never to approach her in her original nudity, but through ceremoniesandsacramentsthatwrestherfromtheearthandfleshand metamorphose her into a human creature: thus the magic she possesses is channeled as lightning has been since the invention of lightningrodsandelectricpowerplants. He loves her becausesheishis,hefearsherbecausesheremainsother;butitisas thefearedotherthatheseekstomakehermostdeeplyhis:thisiswhat willleadhimtoraisehertothedignityofapersonandtorecognize herashispeer. Butonthecontrary,Mitra,Numa,theBrahman women,andtheFlamenwivesrepresentreasonablelawandorderin the city: so the woman is bound to her husband by a ritualistic marriage,andshecollaborateswithhimtoensurehisdominationover all female forces of nature; in Rome, theflamendialis resigns from 223 his position if his wife dies. It has already been seen that the Laws of Manu promisedalegalwifethesameparadiseasherspouse. Themorethe malebecomesindividualizedandclaimshisindividuality,themorehe will recognize an individual and a freedom in his companion. The Greek man cannot find the peer he wants in a woman who was prisoner of the gynaeceum:soheconfershisloveonmalecompanions,whoseflesh, likehisown,isendowedwithaconsciousnessandafreedom,orelse hegiveshislovetohetaeras,whoseindependence,culture,andspirit madethemnearequals. The Roman citizen recognizes a person in the matron; in Cornelia or in Arria, he possesses his double. Paradoxically,itwasChristianitythatwastoproclaimtheequalityof man and woman on a certain level. Christianity detests the flesh in her; if she rejects the flesh, she is, like him, a creature of God, redeemed by the Savior: here she can take her place beside males, among those souls guaranteed celestial happiness.
The authors speculate on the importance of the findings with regard to nickel induced contact allergies spasms back generic imuran 50mg on-line. P38 phosphorylation was seen only after prolonged treatment with both agents together muscle spasms 72885 discount imuran 50mg free shipping. These authors used a hemolytic plaque technique to determine the number of specific antibody-producing spleen cells muscle relaxant renal failure generic imuran 50mg without prescription. The exposed animals showed a significant decrease in splenic antibody-forming cells following a challenge with a T-lymphocyte dependent antigen (Graham et al spasms nose imuran 50 mg low price. Using a criterion of -100 plaques/10 6 cells as a significant effect (a reduction of more than double the background) muscle relaxant yoga generic imuran 50mg free shipping, we obtained a good fit to a linear model (P =0 spasms rectal area generic 50mg imuran overnight delivery. Some of the immunologic effects of nickel in exposed rodents in vivo are summarized in Table 20 muscle relaxant over the counter walgreens order imuran 50mg. Mice also exhibited impairment of pulmonary macrophage function in addition to decreases in antibody-forming spleen cells with inhalation exposure to Ni 3 S2 or NiO (Haley et al muscle relaxant 771 purchase imuran 50 mg line. Natural killer cell activity measured by splenic cytotoxic activity to tumor cells as well as by clearance of melanoma tumors in vivo was suppressed in two strains of mice exposed to intramuscular injections of 18. They also demonstrated that suppression of natural killer cell activity could be detected with in vitro and in vivo assays and that reduction of natural killer cell activity was not associated with either a reduction in spleen cellularity or the production of suppressor cells. Their findings confirmed those reported by other investigators on the immunosuppressive effects of nickel compounds on circulating antibody titers to T 1 phage in rats (Figoni and Treagan, 1975), on antibody response to sheep erythrocytes (Graham et al. Similar exposures of rabbits to chlorides of cadmium, cobalt, or copper did not reduce lysozyme activity. The similarity of the quantitative dose responses for nickel-induced cytokine suppression may indicate a common mode of action. The authors reported that the minimum plasma concentrations of nickel required to provoke immunosuppression are in the range 209 to 585 ng/ml. The data demonstrate that NiCl 2 suppresses T-cell function and promotes an immunosuppressive macrophage phenotype in rats. Prior to infection with Listeria monocytogenes (5 x 104 cells) soluble nickel alone or in metal mixture produced no more lung injury than saline controls. Following infection nickel-treated animals had increased bacterial lung burden and body weight decrease. Ni alone and in mixtures increased reactive oxidants in the lung and was most important in suppressing Tcell activity following infection. Weight decreases in the mixes without Fe or Al indicate that iron and aluminum may act antagonistically to nickel. Toxic effects from airborne substances may be due to exposure via the skin, eyes, and upper and lower respiratory tract. Systemic effects, such as hemolysis or central nervous system injury, may result from absorption of material through the lungs, and, to a lesser extent, through the skin. For a toxic endpoint to be considered due to acute exposure, the effects do not have to be observed immediately. Firstly, human studies are preferred if they are of sufficient quality in terms of endpoint relevance, numbers of subjects, dose response, study design etc. Most often we rely on animal studies, which generally are more available and have better dosimetry data than human studies. We favor studies that provide a dose response that we can analyze with either quanta! Human data were limited to case reports and small occupational clinical or epidemiological studies with limited reporting and inadequate exposure data. It involved an adequate number of animals per dose group (14-29) and each group was compared with its own controls. Interspecies and individual variabilities were represented by the usual defaults of 10 and 30, respectively. A model was used to account for rat to human differences in upper and lower airway deposition of nickel particles and it seems likely that deposition is the key event leading to subsequent lung toxicity. There is also pharmacokinetic uncertainty, but this is somewhat lessened by the deposition model which was also appled to several child lung structures. Repeated exposures to airborne nickel may have a greater impact on infants and children than on adults due to its targeting of the immune system and lung function, and its asthma inducing capability. These studies all showed similar non-carcinogenic effects in rats and mice, regardless of the form of nickel administered. It therefore appears that soluble and insoluble forms of nickel cause similar effects in rodents. Note that in Table 17 all of the child models show higher airway deposition fractions than adult (0. For the present time we propose to continue using the simple deposition fraction ratio as providing the most direct and unmanaged value without additional assumptions about clearance rates and adult values etc. The value of 10 addresses potential increased sensitivity of infants and children vs. The authors found a weak but positive dose response for pulmonary fibrosis and cumulative nickel exposure expressed as (mg Ni/m 3)-yr. The best model fit to the data was obtained with the unadjusted data on soluble nickel of 0. Converting this value to a lifetime continuous value (8/24 hr x 517 days x 1/70 yr) gives 1. We assumed that alveolar deposition was the key event leading to subsequent lung toxic effects. We applied a factor of -V10 for pharmacodynamic differences between mice and humans. A subfactor of 10 was used to account for the anticipated greater sentitivity of infants and children to continuous exposure to airborne nickel oxide particles. A subfactor of -V10 was applied for pharmacokinetic differences between children and adults. However, it is clear from many case reports that allergies and dermatitis can occur in exposed workers. A host of subacute and subchronic animal studies have shown nickel to affect certain immunological responses unrelated to hypersensitivity, but the applicability of these results to chronic human exposures and responses involves considerable uncertainty. Furthermore, data show that nickel may precipitate onset of asthma in occupational settings. The health effects data for nickel oxide indicate that its adverse pulmonary effects were less severe (absence of fibrosis, lower chronic lung inflammation severity scores) at higher doses than the pulmonary effects observed for nickel sulfate and nickel subsulfide. It should be noted tha although the non-neoplastic lung effects seen in the animal studies discussed above were relatively mild, similar effects in humans may be serious or even fatal. The major areas of uncertainty are the lack of adequate human exposure data and the lack of lifetime toxicity studies in any non-rodent species. Nickel targets the immune system and the lung, which are likely a more susceptible system and organ in exposed infants and children. The adverse impacts of nickel compounds on the respiratory and immune systems (including asthma), and also the increased perinatal mortality and reduced birth weight observed in animal studies of reproductive toxicity (see Section 6), are among the types of effect leading to the potential for differential impacts on infants and children. Cytoplasmic dissolution of phagocytized crystalline nickel sulfide particles: A prerequisite for nuclear uptake of nickel. Evaluation of toxic metals in biological samples (scalp hair, blood and urine) of steel mill workers by electrothermal atomic absorption spectroscopy. Evaluation of cadmium, lead, nickel and zinc status in biological samples of smokers and nonsmokers hypertensive patients. Primary particulate matter from oceangoing engines in the southern California air basin. Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. Determination of nickel in lung specimens of thirty-nine autopsied nickel workers. Nickel-induced plasminogen activator inhibitor-1 expression inhibits the fibrinolytic activity of human airway epithelial cells. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry. Morphologic and synthetic response of normal and tumor muscle cultures to nickel sulfide. Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for 12 days. Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for twelve days. Comparative inhalation toxicity of nickel sulfate to F344/N rats and B6C3F1 mice exposed for twelve days. Radiographic evidence of pulmonary fibrosis and possible etiologic factors at a nickel refinery in Norway. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Assessment of the uptake and mutagenicity of nickel chloride in Salmonella tester strains. Analysis of metal-induced mutations altering the expression or structure of a retroviral gene in a mammalian cell line. Effect of thiram and dithiocarbamate pesticides on the gastrointestinal absorption and distribution of nickel in mice. Uptake of 63 Ni 2+ in the central and peripheral nervous system of mice after oral administration: Effects of treatment with halogenated 8-hydroxyquinolines. Boscolo P, Andreassi M, Sabbioni E, Reale M, Conti P, Amerio P and Di Gioacchino M. Systemic effects of ingested nickel on the immune system of nickel sensitized women. Health status and sulfur dioxide exposure of nickel smelter workers and civic laborers. Impaired responses of peripheral blood mononuclear cells to nickel in patients with nickel-allergic contact dermatitis and concomitant atopic dermatitis. Association between particulate- and gasphase components of urban air pollution and daily mortality in eight Canadian cities. Technical Support Document: Proposed Identification of Nickel as a Toxic Air Contaminant. Exposure of human keratinocytes and fibroblasts in vitro to nickel sulfate ions induces synthesis of stress proteins Hsp72 and Hsp90. Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metaldependent. Distribution and clearance of 63 Ni administered as 63 NiCl 2 in the rat: lntratracheal study. Studies in human lactation 3: molybdenum and nickel in human milk during the first month of lactation. Role of oxidative stress in nickel chlorideinduced cell injury in rat cortical slices. Nickel ions increase histone H3 lysine 9 dimethylation and induce transgene silencing. Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(ll). External and internal exposure to the antigen in the hand eczema of nickel allergy. Nonrandom chromosomal alterations in nickeltransformed Chinese hamster embryo cells. Phagocytosis, cellular distribution and carcinogenic activity of particulate nickel compounds in tissue culture. Alteration of testicular biochemistry during protein restriction in nickel treated rats. Effect of nickel on testicular nucleic acid concentrations of rats on protein restriction. Effect of nickel sulfate on testicular steroidogenesis in rats during protein restriction. Hypoxia Inducible Factor-1 aindependent suppression of aryl hydrocarbon receptor-regulated genes by nickel. Chromosomal aberrations and sister chromatid exchanges of peripheral blood lymphocytes in Chinese electroplating workers: Effect of nickel and chromium. Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells. Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice. Evaluation of tissue disposition, myelopoietic, and immunologic responses in mice after long-term exposure to nickel sulfate in the drinking water. Effects of nickel chloride on lactating rats and their sucking pups, and the transfer of nickel through rat milk. Comparative toxicity of nickel oxide, nickel sulfate, and nickel subsulfide after 12 days of inhalation exposure to F344/N rats and B6C3F1 mice. Lung toxicity after 13-week inhalation exposure to nickel oxide, nickel subsulfide, or nickel sulfate hexahydrate in F344/N rats and B6C3F1 mice. Hyperthermia as a teratogen: A review of experimental studies and their clinical significance. Mortality experience among employees at a hydrometallurgical nickel refinery and fertilizer complex in Fort Saskatchewan, Alberta (1954-95). Chromosome aberrations in peripheral blood lymphocytes of welders and characterization of their exposure by biological samples analysis. Toxicokinetics of nickel in rats after intratracheal administration of a soluble and insoluble form. The pulmonary effects and clearance of intratracheally instilled NbS 2 and Ti0 2 in mice. Effect of Ni 2+ on the testosterone production of mouse primary Leydig cell culture. Forti E, Salovaara S, Cetin Y, Bulgheroni A, Tessadri R, Jennings P, Pfaller W and Prieto P. In vitro evaluation of the toxicity induced by nickel soluble and particulate forms in human airway epithelial cells. A mathematical model of the in vitro keratinocyte response to chromium and nickel exposure. Transcriptional profiling defines the effects of nickel in human epidermal keratinocytes. Single and multiple early afterdepolarization caused by nickel in rat atrial muscle. Carcinogenicity of occupational nickel exposures: An evaluation of the epidemiologic evidence. Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(ll) in human T hybridoma cells. The immunotoxicity of three nickel compounds following 13-week inhalation exposure in the mouse. Particle size distributions of metal and non-metal elements in an urban near-highway environment. Atomic absorption spectrometry of nickel, copper, zinc, and lead in sweat collected from healthy subjects during sauna bathing. Increased nickel concentrations in body fluids of patients with chronic alcoholism during disulfiram therapy. Horie M, Nishio K, Fujita K, Kato H, Nakamura A, Kinugasa S, Endoh S, Miyauchi A, Yamamoto K, Murayama H, Niki E, lwahashi H, Yoshida Y and Nakanishi J. Ultrafine NiO particles induce cytotoxicity in vitro by cellular uptake and subsequent Ni(ll) release. Horie M, Fukui H, Nishio K, Endoh S, Kato H, Fujita K, Miyauchi A, Nakamura A, Shichiri M, Ishida N, Kinugasa S, Morimoto Y, Niki E, Yoshida Y and lwahashi H. Evaluation of acute oxidative stress induced by NiO nanoparticles in vitro and in vivo. Quantitative mammalian cell mutagenesis and a preliminary study of the mutagenic potential of metallic compounds. Deposition and clearance models of Ni compounds in the mouse lung and comparisons with the rat models. Respiratory health effects of long-term exposure to different chromium species in stainless steel production. In: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Inflammatory responses and mucus secretion in rats with acute bronchiolitis induced by nickel chloride. Effect of thiuram sulphides on the uptake and distribution of nickel in pregnant and non-pregnant mice. Mobilization of nickel by potassium ethylxanthate in mice: comparison with sodium diethyldithiocarbamate and effect of intravenous versus oral administration. Characterization of lymphocyte subpopulations and cytokine profiles in peripheral blood of nickel-sensitive individuals with systemic contact dermatitis after oral nickel exposure. Ji W, Yang L, Yu L, Yuan J, Hu D, Zhang W, Yang J, Pang Y, Li W, Lu J, Fu J, Chen J, Lin Z, Chen Wand Zhuang Z. Nickel sulfate induces locationdependent atrophy of mouse olfactory epithelium: Protective and proliferative role of purinergic receptor activation. Long-term inhalation exposure to nickel nanoparticles exacerbated atherocslerosis in a susceptible mouse model.
Does not bind to plasma proteins and has an apparent volume of distribution of 16 L muscle relaxer 7767 buy imuran 50 mg visa. As observed with cisplatin back spasms 6 months pregnant purchase 50mg imuran otc, carboplatin undergoes aquation reaction in the presence of low concentrations of chloride muscle relaxant commercial imuran 50 mg mastercard. Bone marrow/stem cell transplant setting-Doses up to 1600 mg/m2 divided over several days muscle relaxant tincture 50mg imuran free shipping. Drug Interaction 1 Myelosuppressive agents-Increased risk of myelosuppression when carboplatin is combined with other myelosuppressive drugs muscle relaxer zoloft 50mg imuran with visa. Chemotherapeutic and Biologic Drugs 89 C Drug Interaction 2 Paclitaxel-Carboplatin should be administered after paclitaxel when carboplatin and paclitaxel are used in combination spasms right side under ribs 50mg imuran with amex. This sequence prevents delayed paclitaxel excretion muscle spasms zyprexa order imuran 50 mg with visa, which results in increased paclitaxel drug levels and potentially increased host toxicity muscle relaxant starting with z 50 mg imuran for sale. Although carboplatin is not as emetogenic as cisplatin, pretreatment with antiemetic agents is strongly recommended. Contraindicated in patients with a history of severe allergic reactions to cisplatin, other platinum compounds, or mannitol. Risk of hypersensitivity reactions increases from 1% to 27% in patients receiving more than seven courses of carboplatin-based therapy. This skin test identifies patients in whom carboplatin may be safely administered. Patients older than 65 years and/or previously treated with cisplatin may be at higher risk for developing neurologic toxicity. Metabolism Carfilzomib is rapidly and extensively metabolized by peptidase cleavage and epoxide hydrolysis. Carfilzomib is rapidly cleared with a half-life of about 1 hour on day 1 of cycle 1. Dosage Range Recommended dose for cycle 1 is 20 mg/m2/day and if tolerated, the dose can be increased to 27 mg/m2/day for cycle 2 and all subsequent cycles. Closely monitor pulmonary status given the risk of pulmonary arterial hypertension and pulmonary complications. Monitor for infusion-related events, which can occur immediately following or up to 24 hours after drug administration. Patients should be well hydrated prior to drug administration to reduce the risk of renal toxicity. Patients with high tumor burden are at increased risk for developing tumor lysis syndrome. Brain tumors-Glioblastoma multiforme, brain stem glioma, medulloblastoma, astrocytoma, and ependymoma. Drug Interaction 2 Amphotericin B-Amphotericin B enhances the cellular uptake of carmustine, thus resulting in increased toxicity, including renal toxicity. Drug Interaction 4 Phenytoin-Carmustine may decrease the plasma levels of phenytoin. Repeated cycles should not be given before 6 weeks, given the delayed and potentially cumulative myelosuppressive effects of carmustine. Toxicity 4 Hepatotoxicity with transient elevations in serum transaminases develops in up to 90% of patients within 1 week of therapy. At cumulative doses greater than 1400 mg/m2, interstitial lung disease and pulmonary fibrosis in the form of an insidious cough, dyspnea, pulmonary infiltrates, and/or respiratory failure may develop. Toxicity 8 Increased risk of secondary malignancies, especially acute myelogenous leukemia and myelodysplasia. Elimination is mainly hepatic with excretion in feces (92%) with nearly 70% as unchanged parent drug. Drug Interaction 1 Drugs such as ketoconazole, itraconazole, erythromycin, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole may decrease the rate of metabolism of ceritinib, resulting in increased drug levels and potentially increased toxicity. Use with caution in patients with hepatic dysfunction, as ceritinib is eliminated mainly via the liver. However, the drug has not been evaluated in patients with moderate to severe hepatic dysfunction. May need to suspend, dose-reduce, or permanently stop ceritinib with the development of drug-induced hepatotoxicity. Closely monitor blood sugar levels especially in diabetic patients or in those on steroids. Ceritinib should be taken on an empty stomach and should not be taken within 2 hours of a meal. Avoid Seville oranges, starfruit, pomelos, grapefruit, and grapefruit products while on ceritinib therapy. Cetuximab should be used with caution in patients with known hypersensitivity to murine proteins and/or any individual components. Development of skin toxicity appears to be a surrogate marker for cetuximab clinical activity. Use with caution in patients with underlying interstitial lung disease as these patients are at increased risk for developing worsening of their interstitial lung disease. In patients who develop a skin rash, topical antibiotics such as clindamycin gel or erythromycin cream or either oral clindamycin, oral doxycycline, or oral minocycline may help. About 90% of patients experience severe infusion reactions with the first infusion despite the use of prophylactic antihistamine therapy. Electrolyte status should be closely monitored, especially serum magnesium levels, as hypomagnesemia has been observed with cetuximab treatment. C Toxicity 1 Infusion-related symptoms with fever, chills, urticaria, flushing, fatigue, headache, bronchospasm, dyspnea, angioedema, and hypotension. Usually mild-to-moderate in severity and observed most commonly with administration of the first infusion. Observed in less than 1% of patients and more frequent in patients with underlying pulmonary disease. Toxicity 6 Paronychial inflammation with swelling of the lateral nail folds of the toes and fingers. Metabolism Metabolized extensively by the liver cytochrome P450 system to both active and inactive forms. Parent drug and its metabolites are eliminated by the Chemotherapeutic and Biologic Drugs 105 C kidneys, and 60% of drug metabolites are excreted in urine within 24 hours. Drug Interactions Phenobarbital, phenytoin, and other drugs that stimulate the liver P450 system-Concurrent use of chlorambucil with these drugs may increase its metabolic activation, leading to increased formation of toxic metabolites. Contraindicated within 1 month of radiation and/or cytotoxic therapy, recent smallpox vaccine, and seizure history. Use with caution when combined with allopurinol or colchicine as drug-induced hyperuricemia may be exacerbated. Therapy should be discontinued promptly if generalized skin rash develops as this side effect may rapidly progress to erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome. Toxicity 4 Pulmonary fibrosis and pneumonitis are dose-related and potentially lifethreatening. Children with nephrotic syndrome and patients receiving large cumulative doses are at increased risk. Toxicity 6 Skin rash, urticaria on face, scalp, and trunk with spread to legs seen in the early stages of therapy. Toxicity 8 Increased risk of secondary malignancies, including acute myelogenous leukemia. Distribution Widely distributed to all tissues with highest concentrations in the liver and kidneys. Within the cytoplasm of the cell, low concentrations of chloride (4 mM) favor the aquation reaction whereby the chloride atom is replaced by a water molecule, resulting in a highly reactive species. Platinum clearance from plasma proceeds slowly after the first 2 hours due to covalent binding with serum proteins, such as albumin, transferrin, and g-globulin. Drug Interaction 1 Phenytoin-Cisplatin decreases pharmacologic effect of phenytoin. For this reason, phenytoin dose may need to be increased with concurrent use with cisplatin. Drug Interaction 2 Amifostine, mesna-The nephrotoxic effect of cisplatin is inactivated by amifostine and mesna. Drug Interaction 3 Aminoglycosides, amphotericin B, other nephrotoxic agents-Increased renal toxicity with concurrent use of cisplatin and aminoglycosides, amphotericin B, and/or other nephrotoxic agents. Drug Interaction 4 Etoposide, methotrexate, ifosfamide, bleomycin-Cisplatin reduces the renal clearance of etoposide, methotrexate, ifosfamide, and bleomycin, resulting in the increased accumulation of each of these drugs. Drug Interaction 5 Etoposide-Cisplatin may enhance the antitumor activity of etoposide. Drug Interaction 7 Paclitaxel-Cisplatin should be administered after paclitaxel when cisplatin and paclitaxel are used in combination. Drug Interaction 8 Aminoglycosides, furosemide-Risk of ototoxicity is increased when cisplatin is combined with aminoglycosides and loop diuretics such as furosemide. Contraindicated in patients with known hypersensitivity to cisplatin or other platinum analogs. Usual approach is to give at least 1 liter before and 1 liter post-drug treatment of 0. With higher doses of drug, more aggressive hydration should be considered with at least 2 liters of fluid administered before drug. Use with caution in patients with hearing impairment or pre-existing peripheral neuropathy. Baseline audiology exam and periodic evaluation during therapy are recommended to monitor the effects of drug on hearing. Avoid aluminum needles when administering the drug because precipitate may form, resulting in decreased potency. Cisplatin is inactivated in the presence of alkaline solutions containing sodium bicarbonate. Electrolyte abnormalities, mainly hypomagnesemia, hypocalcemia, and hypokalemia, are common. Neutropenia and thrombocytopenia are more Chemotherapeutic and Biologic Drugs 111 C pronounced at higher doses. Tends to occur after several cycles of therapy and risk increases with cumulative doses. Toxicity 6 Hypersensitivity reactions consisting of facial edema, wheezing, bronchospasm, and hypotension. Toxicity 7 Ocular toxicity manifested as optic neuritis, papilledema, and cerebral blindness. Toxicity 10 Vascular events, including myocardial infarction, arteritis, cerebrovascular accidents, and thrombotic microangiopathy. Metabolism Extensively metabolized intracellularly to nucleotide metabolite forms. Intracellular concentrations of phosphorylated metabolites exceed those in plasma by several hundred-fold. If patient does not respond to one course, it is unlikely that a response will be seen with a second course of therapy. Patients are at increased risk for opportunistic infections, including herpes, fungus, and Pneumocystis jiroveci. Allopurinol should be given before initiation of therapy to prevent hyperuricemia. Clofarabine has high affinity for the activating enzyme deoxycytidine kinase and is a more efficient substrate for this enzyme than the normal substrate deoxycytidine. As clofarabine is excreted mainly by the kidneys, drugs with known renal toxicity should be avoided during the 5 days of drug treatment. Toxicity 1 Myelosuppression is dose-limiting with neutropenia, anemia, and thrombocytopenia. Pericardial effusion observed in up to 35% of patients, but usually minimal to small and not hemodynamically significant. Toxicity 4 Hepatic dysfunction with elevation of serum transaminases and bilirubin. Toxicity 5 Increased risk of opportunistic infections, including fungal, viral, and bacterial infections. Toxicity 6 Renal toxicity with elevation in serum creatinine observed in up to 10% of patients. Toxicity 7 Cardiac toxicity as manifested by left ventricular dysfunction and tachycardia. Chemotherapeutic and Biologic Drugs 119 C Distribution Extensive binding (90%) to plasma proteins. Elimination is hepatic with excretion in feces (,60%), with renal elimination accounting for 20% of an administered dose. Unchanged crizotinib represents approximately 50% of an administered dose in feces and about 2% in urine. Drug Interaction 1 Drugs such as ketoconazole, itraconazole, erythromycin, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole may decrease the rate of metabolism of crizotinib, resulting in increased drug levels and potentially increased toxicity. Use with caution in patients with hepatic dysfunction as crizotinib has not been studied in this setting. Little to no data is available in patients with severe renal dysfunction and end-stage renal disease. Patients should be advised against performing activities that require mental alertness, including operating machinery and driving. May need to suspend, dose-reduce, or permanently stop crizotinib with the development of drug-induced hepatotoxicity. Patients should be aware of potential visual changes, including blurry vision, photosensitivity, and flashes/floaters. Careful eye exam should be performed in the setting of new or worsening floaters and/ or photopsia to rule out the presence of retinal detachment. Avoid Seville oranges, starfruit, pomelos, grapefruit, and grapefruit juice while on crizotinib therapy. Toxicity 3 Pulmonary toxicity with increased cough, dyspnea, fever, and pulmonary infiltrates. Chemotherapeutic and Biologic Drugs 121 C Toxicity 6 Visual side effects, including diplopia, blurry vision, visual field defects, floaters/flashes, visual brightness, and reduced visual acuity. Toxicity 7 Peripheral sensory and/or motor neuropathy have been reported in up to 10% of patients. Minimal binding of parent drug to plasma proteins; Chemotherapeutic and Biologic Drugs 123 C however, about 60% of the phosphoramide mustard metabolite is bound to plasma proteins. Metabolism Extensively metabolized in the liver by the cytochrome P450 system to both active and inactive forms. The active forms are 4-hydroxycyclophosphamide, phosphoramide mustard, and acrolein. Drug Interaction 1 Phenobarbital, phenytoin, and other drugs that stimulate the liver P450 system-Increase the rate of metabolic activation of cyclophosphamide to its cytotoxic metabolites. Drug Interaction 3 Digoxin-Cyclophosphamide decreases the plasma levels of digoxin by activating its metabolism in the liver. Encourage patients to empty bladder several times daily (on average, every 2 hours) to reduce the risk of bladder toxicity. Time of onset is variable and may begin within 24 hours of therapy or may be delayed for up to several weeks. Uroprotection with mesna and hydration must be used with high-dose therapy to prevent bladder toxicity. Chemotherapeutic and Biologic Drugs 125 C Toxicity 7 Increased risk of secondary malignancies, including acute myelogenous leukemia and bladder cancer, especially in patients with chronic hemorrhagic cystitis.
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