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Vice Chair, New York University School of Medicine

In some species, CaE is also found in high concentrations in plasma; plasma CaE is synthesized in the liver and secreted into the circulation via the Golgi apparatus of hepatocytes (Miller et al. Secretion of CaE appears to be controlled by the presence or absence of a retention signal at the carboxy terminal of the enzyme (Figure 8. Data points (from lower left to upper right of graph) for species were monkey, rabbit, guinea pig, rat, and mouse. The authors note that some of the in vivo differences seen in sensitivity and protection may be due to variations in the circulatory pharmacodynamics of the different organophosphorus compounds, such that those inhibitors that distribute more slowly from circulation are more readily scavenged. This concept provided early support for the feasibility of using scavengers to protect against exposures to nerve agent. Ultimately, the goal of research on scavenger molecules is to generate a means to protect humans from the toxic effects of nerve agents. Remaining four animals were normal, survived and they were held for long-term observations. They further noted that to be effective, a scavenger had to be present before exposure to the organophosphorus compound, because (as discussed above) the nerve agent had to be scavenged within one blood circulation time period (Raveh et al. In the final paper in this series, the authors report similar protection results against a 3. They also report considerable protection against soman-induced behavioral deficits in a spatial discrimination task. At necropsy, 7 or 14 days after surviving the nerve agent challenge, all tissues appeared normal upon light microscopic examination. No signs of poisoning were observed in the experimental animals during the efficacy studies. Of six animals challenged, one died after the final challenge dose of soman (total dose of 5. The remaining animals displayed no immediate signs of poisoning and exhibited no lasting effects of poisoning as assessed by blood chemistry examinations and long-term (>20 month) observations. They found that the lyophilized form of the enzyme had a shelf life of over 24 months at 4, 25, or 378C. In addition, the material, when reconstituted, showed no alteration in its in vivo properties with respect to the pharmacokinetics in mice or rhesus monkeys. The overall conclusion from these studies was that plasma-derived Hu-BuChE was both safe and efficacious as a biological scavenger. Army transitioned the plasmaderived Hu-BuChE to advanced development in October 2004. Nerve Agent Bioscavengers 185 Plasma-derived Hu-BuChE represents a first-generation biological scavenger. This material is obtained from outdated blood and so the overall availability is dependent on the quantity of outdated blood available at any given time. Because this supply is dependent on the extent of donor participation and the need for blood under other circumstances such as natural disasters or unforeseen medical emergencies, basic research efforts are being focused on the development of Hu-BuChE from a recombinant source. If successful, such efforts would allow for a constant supply of material of reproducible purity and activity without affecting the supply of whole blood, collected for other purposes. There are a variety of potential sources of human recombinant protein, to include material from transgenic plants (Mor et al. Reported attempts to express functional Hu-BuChE in bacteria or yeast have failed (Masson et al. To date, recombinant Hu-BuChE (rHuBuChE) enzymes purified from transgenic plants (Mor et al. Studies with rHuBuChE from the milk of transgenic goats have yielded efficacy results in guinea pigs that are very similar to those described previously (vide supra) with plasma-derived material, that is, complete protection against 5. In its native form, rHuBuChE from transgenic goat milk is primarily either a dimer or a monomer, in contrast to the plasma-derived material which is a tetramer. Additionally, the goat milk derived rHu-BuChE has a glycosylation pattern different from that of the plasma material (Garcia et al. As a result, goat milk derived rHuBuChE has a different pharmacokinetic profile, with a shorter circulatory half-life. The rHuBuChE from goat milk did not evoke any behavioral side effects of its own in guinea pigs, and in addition to survival, animals protected were devoid of any of the typical postpoisoning side effects such as the delayed recovery of function seen when traditional therapy is used. These preliminary results suggest that some form of a recombinant stoichiometric bioscavenger can be developed, thereby providing sufficient material to protect the entire U.

Of course, it will not eliminate the need for other protective and therapeutic systems. Pyridostigmine is most appropriate for anticipated exposure to nerve agents capable of rapid ``aging, such as soman. Several other anti-ChEs that do cross the blood-barrier, including physostigmine, Health Effects of Low-Level Exposure to Nerve Agents 89 tacrine, and huperzine A, have been found to offer better protection than pyridostigmine, but at the cost of undesirable central effects. It has been suggested that human BuChE from plasma participates in the endogenous scavenging of naturally occurring drugs (e. A novel approach is to use enzymes, whether wild type or altered through directed mutation, to scavenge these highly toxic nerve agents before they attack their intended targets. The accumulated work has shown that if a scavenger is present at the time of nerve agent exposure, rapid reduction of toxicant levels is observed (Lenz et al. This reduction is so rapid and profound that the need to administer a host of pharmacologically active drugs as antidotes is, in theory, eliminated. The promise afforded by the use of scavenger enzymes is so great and their applications so diverse that three different chapters in this text (see Chapters 7, 8, and 9) are devoted to their discussion. It also increased its emphasis on research, both epidemiological and experimental, into the health effects of exposure to nerve chemical warfare agents, with the intent on improving medical response to chemical agents. We believe that a comprehensive assessment of the health consequences of nerve agent chemical weapons is unfolding and has already begun to improve our understanding of this problem. Finally, it has already begun to improve our ability to deal with these health consequences effectively. Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents. Chronic neurologic sequelae to cholinesterase inhibition among agriculture pesticide applicators. Development of a guinea pig model for low-dose, long-term exposure to organophosphorus nerve agents. Behavioral effects of occupational exposure to organophosphate pesticides in female greenhouse planting workers. Behaviorally augmented versus other components in organophosphate tolerance: the role of reinforcement and response factors. Anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by highly toxic organophosphorus compounds. Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents. Pharmacokinetic studies of intramuscular midazolam in guinea pigs challenged with soman. Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman. Hypothermia: limited tolerance to repeated soman administration and cross-tolerance to oxotremorine. The relationship between the chemical structures and neurotoxicity of alkyl organophosphorous compounds, Br. Central nervous system effects of acute organophosphate poisoning in a two-year follow-up. Age related effects of pesticide exposure on neurobehavioral performance of adolescent farm workers in Brazil. Neurobehavioral effects among workers occupationally exposed to organophosphorous pesticides. Kinetic constants for the inhibition of eel and rabbit brain acetylcholinesterase by some organophosphates and carbamates of military significance. Effects in man of the anticholinesterase compound sarin (isopropyl methyl phosphonofluoridate). Effect on the central nervous system with special reference to the electrical activity of the brain. Anxiety, depression and posttraumatic stress in Iranian survivors of chemical warfare. Decreased brain pathology in organophosphate-exposed rhesus monkeys following benzodiazepine therapy. Response of F344 rats to inhalation of subclinical levels of sarin: exploring potential causes of Gulf War illness.

Also called hepatolenticular degener- other terms referring to the womb, see words beginning with hyster-, hystero-, metr-, metro-, uter-, utero-. Also called flatulence to break wind to bring up gas from the stomach, or to let gas escape from the anus windburn / wIndb n/ noun redness and inflammation of the skin caused by exposure to harsh wind windburn ation [Described 1912. World Health Organization / w ld hel naI zeIn/ noun an organisation, part of the United Nations, which aims to improve health in the world. Also called ensiform cartilage, xixiphoid process phisternum X-linked / eks lIkt/ adjective relating to the genes situated on the X chromosome X-linked disease / eks lIkt dI zi z/ noun a genetic disorder caused by a mutation on the X chromosome which only appears in males. X-rays are used in diagnosis in radiography, and in treating disease by radiotherapy. They grow faster than normal, and their final height is approximately 7cm above average. X-ray screening / eks reI skri nI/ noun a method of gathering information about the X-ray photograph X-ray screening nal organs opaque so that they will show up on the film. In the case of stomach X-rays, people take a barium meal before being photographed (contrast radiography); in other cases, such as kidney X-rays, radioactive substances are injected into the bloodstream or into the organ itself. X-rays are used not only in radiography for diagnosis but as a treatment in radiotherapy as rapidly dividing cells such as cancer cells are most affected. Excessive exposure to X-rays, either as a person being treated, or as a radiographer, can cause radiation sickness. X-ray imaging / eks reI ImId I/ noun the X-ray imaging Y yawn /j n/ noun a reflex action when tired or sleepy, in which the mouth is opened wide and after a deep intake of air, the breath exhaled slowly His yawns made everyone feel sleepy. Symptoms include fever with raspberry-like swellings on the skin, followed in later stages by bone malformation. A deep Z-shaped incision is made to relieve tension in the area of a scar, or to change the direction of a scar. Also called zygoma zygomatic bone / zaI m tIk bn/ noun a bone which forms the prominent part of the cheek and the lower part of the eye socket. Also called cheekbone, malar bone zygomatic process / zaI m tIk prs es/ noun one of the bony projections which form the zygomatic arch zygomycosis / zaI maI ksIs/ noun a disease caused by a fungus which infests the blood vessels in the lungs zygote / zaI t/ noun a fertilised ovum, the first stage of development of an embryo zym- /zaIm/ prefix (used before vowels) 1. There is only one central vertical plane, termed the median or sagittal plane, and this passes through the body from front to back. Two specific horizontal planes are (a) the transpyloric, midway between the suprasternal notch and the symphysis pubis, and (b) the transtubercular or intertubercular plane, which passes through the tubercles of the iliac crests. Views of the body from some different points are shown on the diagram; a view of the body from above is called the superior aspect, and that from below is the inferior aspect. Cephalic means toward the head; caudal refers to positions (or in a direction) towards the tail. Proximal and distal refer to positions respectively closer to and further from the centre of the body in any direction, while lateral and medial relate more specifically to relative sideways positions, and also refer to movements. Ventral refers to the abdomen, front or anterior, while dorsal relates to the back of a part or organ. The hand has a dorsal and a palmar surface, and the foot a dorsal and a plantar surface. Note that flexion of the thigh moves it forward while flexion of the leg moves it backwards; the movements of extension are similarly reversed. Movement and rotation of limbs can be medial, which is with the front moving towards the centre line, or lateral, which is in the opposite direction. Specific terms for limb movements are adduction, towards the centre line, and abduction, which is away from the centre line. Other specific terms are supination and pronation for the hand, and inversion and eversion for the foot. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4200-4661-8 (Hardcover) this book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. Library of Congress Cataloging-in-Publication Data Chemical warfare agents: chemistry, pharmacology, toxicology, and therapeutics / editors, James A.

Syndromes

• Extreme tenderness over the kidney
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There are either longer impulses (first degree block) or missing impulses (second degree block) or no impulses at all (complete heart block), in which case the ventricles continue to beat slowly and independently of the sinoatrial node. It is often painful and sometimes indicates possible health problems, such as fibroids or hypothyroidism. The main idea is that `the nurse does for others what they would do for themselves if they had the strength, the will, and the knowledge. It often occurs after an upper respiratory infection, mostly in children aged two to 11. Hepatitis A is less serious than the B form, which can cause severe liver failure and death. Also called rupture reduction of a hernia putting a hernia back into the correct position hernial / h nil/ adjective referring to a hernia hernial sac / h nil s k/ noun a sac formed where a membrane has pushed through a cavity in the body herniated / h nieItId/ adjective referring to an organ which has developed a hernia herniated disc / h nieItId dIsk/ noun Hering-Breuer reflexes hermaphrodite hermaphroditism hernia hernial hernial sac herniated herniated disc flammation of a sensory nerve, characterised by pain along the nerve and causing a line of blisters to form on the skin, usually found mainly on the abdomen or back, or on the face. It is not known what triggers the development of shingles, though it is known that an adult suffering from shingles can infect a child with chickenpox. Compare bisexual, hoheteropsia heterosexual mosexual heterosexuality / hetrseku lIti/ noun sexual attraction towards persons of the opposite sex heterotopia / hetr tpi/ noun 1. A drink of water, holding the breath and counting, breathing into a paper bag, are all recommended. Hickman catheter / hIkmn k it/, Hickman line / hIkmn laIn/ noun a plastic Hickman catheter high-calorie diet /haI k lri daIt/ noun a diet containing over 4000 calories per day high-density lipoprotein /haI densIti lIp prtin/ noun a lipoprotein with a low percentage of cholesterol. Also called innominate bone hip fracture / hIp fr kt/ noun a fracture of the ball at the top of the femur hip girdle / hIp dl/ noun same as pelhip fracture hip girdle vic girdle hip joint / hIp d Int/ noun the place where the hip is joined to the upper leg. Histamines dilate blood vessels, constrict the cells of smooth muscles and cause an increase in acid secretions in the stomach. Compare heterozygous hook /hk/ noun a surgical instrument with a bent end used for holding structures apart in operations hook hookworm hookworm 180 hospice / hspIs/ noun a hospital which offers palliative care for terminally ill people hospital / hspItl/ noun a place where sick or injured people are looked after hospital bed 1. It is found in the urine during pregnancy, and can be given by human human anatomy human being human chorionic gonadotrophin injection to encourage ovulation and help a woman to become pregnant. People usually receive it in combination with other drugs that increase the output of urine. Opposite hypohyperacidity / haIpr sIdIti/ noun the production of more acid in the stomach than is usual. Also called acidity, acid stomach hyperacousia / haIpr kju zi/ noun same as hyperacusis hyperactive /haIpr ktIv/ adjective very or unusually active hyperactivity /haIpr k tIvti/ noun a condition in which something or someone. Also called longsighthypergalactia hyperglycaemia hyperhidrosis hyperinsulinism hyperkalaemia hyperkeratosis hyperkinesia hyperkinetic syndrome hyperlipidaemia hypermenorrhoea hypermetropia hyperadrenalism / haIpr dri nlIzm/ noun a disorder in which too many adrenal hormones are produced. Compare hypohyperpiesis hyperpituitarism hyperplasia hyperpnoea hyperpyrexia hypersecretion hypersensitive hypersensitivity hypersplenism hypertelorism hypertension hypnotism can be treated with carbimazole. Also called creased rigidity and spasticity of the muscles hypertonic / haIp tnIk/ adjective 1. It hypertensive retinopathy hyperthermia hyperthyroidism hypnotist hypnotist 186 hypodermic syringe / haIpd mIk sI rInd / noun a syringe fitted with a hypodermic needle for injecting liquid under the skin hypofibrinogenaemia / haIp fIbrIn d ni mi/ noun a condition in which there is not enough fibrinogen in the blood. A hypoglycaemic attack can be prevented by eating glucose or a lump of sugar when feeling faint. Compare epispadias hypostasis /haI pstsIs/ noun a condition in which fluid accumulates in part of the body because of poor circulation hypostatic / haIp st tIk/ adjective referring to hypostasis hypostatic eczema / haIpst tIk eksIm/ noun same as varicose eczema hypostatic pneumonia / haIpst tIk nju mni/ noun pneumonia caused by fluid accumulating in the lungs of a bedridden person with a weak heart hyposthenia / haIps i ni/ noun a condition of unusual bodily weakness hypophyseal hypophyseal stalk hypophysectomy hypophysis cerebri hypopiesis hypopituitarism hypoplasia hypoplastic left heart hypopnoea hypoproteinaemia hypoprothrombinaemia hypopyon hyposensitise hyposensitive hyposensitivity hypospadias hypostasis hypostatic hypostatic eczema hypostatic pneumonia hyposthenia hypotension hypoventilation hypotension / haIp tenn/ noun a condition in which the pressure of the blood is unusually low. Compare hypertension hypotensive / haIp tensIv/ adjective having low blood pressure hypothalamic / haIp l mIk/ adjective referring to the hypothalamus hypothalamic hormone / haIp l mIk h mn/ noun same as releasing hypotensive hypothalamic hypothalamic hormone hypothalamus / haIp lms/ noun the part of the brain above the pituitary gland, which controls the production of hormones by the pituitary gland and regulates important bodily functions such as hunger, thirst and sleep. I thought I heard someone shout, but I must have imagined it because there is no one there. The impairment was progressive, but she did not notice that her eyesight was getting worse. Compare excision incisional /In sI nl/ adjective referring to an incision incisional hernia /In sI nl h ni/ noun a hernia which breaks through the abdominal wall at a place where a surgical incision was made during an operation incisor /In saIz/, incisor tooth /In saIz tu / noun one of the front teeth, of which there are four each in the upper and lower jaws, which are used to cut off pieces of food.