Influence of Aspirin on Post Tooth Extraction Bleeding

Influence of Aspirin on Post Tooth Extraction Bleeding ABSTRACT Aim: The aim of the study was to evaluate the influence of aspirin on post extraction bleeding in a clinical setup. Materials and Method: 200 Patients aged between 50 to 65 years, who were indicated for dental extraction was selected from outpatient department of Oral and Maxillofacial Surgery. All the patients were randomly divided in aspirin continuing group (Group A) and aspirin discontinuing group (Group B). After checking all the vital signs extractions were carried out. Bleeding time and clotting time was recorded for evaluation by Chi Square Test. Results: Chi Square test asserted that the bleeding time increased (3.8Â ±0.75) in Group B patients who continued with the antiplatelet therapy while it decreased in Group A patients who discontinued aspirin. Similarly clotting time increased in group B patient and decreased in Group A patient. But in both the groups, bleeding and clotting time remained within normal limits. Conclusion: Assessing most of the dental and medical literature it can be concluded that there is absolutely no need to discontinue anti platelet therapy for any ambulatory dental procedure and even if practitioner wishes to discontinue, it should not be more than 3 days. This is also stated in the guidelines of American Heart Association. Keywords: Anti platelet drugs, Aspirin, Bleeding time, Tooth extraction. INTRODUCTION Medical practitioners commonly advice their patients who are on antiplatelet therapy to either stop or alter their medications prior to surgical procedures due to fear of excessive and uncontrolled bleeding. This is a proven fact that aspirin causes increased risk of intraoperative as well as postoperative bleeding and also increased risk of thromboembolic events such as myocardial infraction and cerebrovascular accidents if the drug is continued1. Thrombotic and thromboembolic occlusions of blood vessels are the main cause of ischaemic events in heart, lungs and brain2. In case of blood vessel injury hemostatic mechanism is responsible for stopping the extravasation. Mainly hemostatic mechanism in characterized by two consecutive phases primary and secondary. Primary mechanism arrests early bleeding as a result of platelet plug formation3. Secondary hemostasis phase is mediated by complex cascade of clotting factors which helps in formation of fibrin clot4. In recent years lot of re search and progress have been made in the field of antiplatelet agents and anticoagulants. These drugs have been utilized for the management of arterial thrombosis also2. Even though a number of antiplatelet and anticoagulant agents have been developed, aspirin and warfarin remains the standard drug of choice5. Development of aspirin dates back to 1897 and is considered as one of the safest and cheapest drug worldwide. A general practitioner Lawrence Craven prescribed low dose aspirin (Baby Aspirin) to his 400 patients and none of them developed myocardial infraction6. This was probably the first time in medical history where aspirin was used to prevent myocardial infarction. Since then it has become the drug of choice for cardiologists. The antithrombotic effect of aspirin is mediated by irreversible inhibition of cyclooxygenase activity in platelets. Phospholipase-A2 acts on the cell membrane to release arachidonic acid on activation. Cyclooxygenase acts on arachidonic acid to produce thromboxane A2. Thromboxane A2 is a potent platelet stimulant leading to degranulation of platelet and platelet aggregation. Aspirin inhibits cyclooxygenase enzyme and decreases the level of platelet stimulant thromboxane A2,5 thus increasing the bleeding time. This is the important reason for a medical practitioner to stop aspirin 3 to 7 days prior to any invasive surgery. The purpose of this study was to investigate the influence of aspirin on post extraction bleeding. MATERIALS AND METHOD This study was conducted at the outpatient Department of Oral and Maxillofacial Surgery. Patients who were on aspirin therapy, aged between 50 to 65 years and who had to undergo tooth extraction were selected for the study. Patients on warfarin, non-steroidal anti-inflammatory drugs, heparin, steroids or suffering from blood disorders and diabetes were excluded from the study. Informed consent was obtained from the patients with the ethical committee clearance. Two hundred patients including both males and females whose teeth were indicated for extraction were included in the study. Patients were randomly divided into Group A and Group B of 100 patients each. Group A patients continued to receive aspirin preoperatively while Group B patients were asked to stop aspirin 7 days prior to extraction. Pre operatively all the vital signs (Blood Pressure and Pulse) were measured. Bleeding time (White and Lee technique) and clotting time (Ivy’s technique) was calculated. Extractions were carried out only if the above parameters were within normal range. After tooth was extracted presence or absence of bleeding and bleeding time was recorded. Analgesics and antibiotics were prescribed as needed for pain and infection control. Chi square test was used to evaluate the relative frequencies of patients in both groups. Differences of parametric variables were tested with analysis of variance. RESULTS After applying Chi square test, mean bleeding time was calculated as 2.1Â ±0.52 minutes in the patients who discontinued baby aspirin (Group B) 7 days prior to extraction. Bleeding time of Group A patients who continued aspirin through the entire study was found to be 3.8Â ±0.75 minutes. This difference was statistically significant (p=0.002) [Table 1]. Although there is significant increase in the bleeding time of Group A patients it should be noted that bleeding time of both the groups was within the normal limits. Clotting time of Group B patients was 3.8Â ±0.75 and Group A was 4.7Â ±0.74 which was also within the normal limits (Normal range according to Ivy’s Method: 3 to 5 minutes). DISCUSSION Historically aspirin was used as an anti-inflammatory, analgesic and antipyretic drug for a short period of disease activity. Lawrence Craven in 1950 reported for the first time its long term use to prevent myocardial infarction6. He advocated a lower dose for antiplatelet action. Antiplatelet activity of aspirin occurs at doses ranging as low as 40 mg/day7 to 3208 mg daily. Doses above 320 mg/day decrease the effectiveness of aspirin as antiplatelet agent due to inhibition of prostacyclin production9. However recent clinical trial indicates that 160 mg/day is optimal for antiplatelet action10. In emergencies where urgent antithrombotic action is required a loading dose of 300 mg is advocated9. Usually in United States daily dose of 81 mg, 160 mg or 325 mg are prescribed while in Europe and other countries daily dose of 75 mg, 150mg or 300 mg are prescribed10. Risk of continuing aspirin therapy prior to surgery is that, with the alteration of platelet function longer time period is required to stop the bleeding from a surgical site. This is attributed to the alteration in primary hemostatic mechanism. Burger et al stated that, in patients on aspirin, the average risk of bleeding increases 1.5 folds. At the same time there is a risk in stopping the aspirin prior to surgery leading to a potential risk of rebound of thromboembolic vascular events. On stopping aspirin thromboxane A2 activity increases to a greater extent with decrease in fibrinolytic activity11. Ferrari et al showed the existence of biological platelet rebound phenomenon on interruption of aspirin therapy. This could create a prothrombotic state which may lead to fatal thromboembolic events. Approximately 20% of these episodes are fatal and another 40% can lead to permanent disability12. Practitioners who advocate the stoppage of aspirin have been debating among themselves regarding the time limit to stop aspirin. Literature wise the effect of aspirin on platelets is irreversible. The effect lasts for 7 to 10 days which is the life span of platelets13, 14. Therefore since early days it was recommended to stop aspirin 7 days prior to surgical procedure15-19. Sonksen et al in their study comprising of 52 healthy individuals showed that withdrawal of aspirin for more than 5 days was not recommended20. Wahl et al advocated that aspirin should be discontinued for 3 days only as after 3 days of interruption of aspirin, sufficient number of newer platelets would be present in circulation for hemostasis21, 22. Now again the debate arises whether to stop aspirin therapy or not? Fear for uncontrolled bleeding encourages the practitioners to discontinue the aspirin therapy. Few studies have shown that there is always an increased risk of bleeding in patients continuing aspirin23, 24. Hence few studies recommended stopping of aspirin therapy prior to surgical procedure17, 19, 25. However if the aspirin therapy is discontinued, there is increased risk of thromboembolic events which can be fatal but none of these have been reported in dental literature. Fijnheer et al in his article mentioned that there is scarcity of literature regarding dental surgeries involving patients on aspirin medication26. Little et al recommended that unless bleeding time is increased above 20 minutes aspirin affected platelets would not cause significant bleeding complication22. Similar claims were made by Sonksen et al and Gaspar et al20, 27. Canigral et al conducted a research involving surgical extraction in patients on antithrombotic therapy. In 92% cases bleeding stopped within 10 minutes with pressure alone. This result was in accordance with the present study4. Gaspar et al advocated that ambulatory oral surgical procedures can be performed in patients without discontinuing the use of aspirin27. A recent recommendation from American Heart Association and American College of Cardiology is that, either continuing aspirin or clopidogrel therapy for minor oral surgical procedures in patients with coronary artery stents or delaying treatment until prescribed regimen will be complicated. The present study demonstrated that there was significant increase in the bleeding time in both the groups but in no case it was difficult to stop the bleeding. Although bleeding time increased in the Group A patients but it still remained within the normal range, regardless of whether patients continued or discontinued their aspirin therapy28, 29, 30. This result was similar to the study done by Canigral et al4. Valerin et al conducted a study with 17 patients randomized to aspirin and 19 to placebo and found no differences in bleeding outcomes for patients on aspirin. This finding suggested that there was no need to discontinue aspirin prior to any ambulatory oral surgical procedures31. Adchariyapetch compared the postoperative bleeding on subjects who stopped or continued taking the aspirin for seven days prior to extraction. The mean bleeding time in both the groups was in normal range. After the procedure there was no difficulty in achieving hemostasis. Therefore they concluded that surgical extraction did not require discontinuation of antiplatelet therapy32. Matocha in his study concluded that risk of bleeding after dental extraction is very minimal in the patients with aspirin therapy and did not exceed 0.2 to 2.3%33. Murphy et al concluded with a survey that 86% of the dental practitioners who advised the patient to stop antiplatelet drugs prior to dental extraction did so with the consultation of the patient’s physician and found that the protocol followed by the physicians and dentists was not based on the current recommendations and guidelines34. Napenas et al concluded that the risk of stopping antiplatelet therapy and predisposing the patient to thromboembolic events overweighed the minimal risk of bleeding from dental procedures. Similar results were found in the study done by Nielsen et al35. Wahl in a research study reported that in 950 patients receiving anticoagulation therapy, only 12 required (

The Twilight Saga 2: New Moon Chapter 10 THE MEADOW

JACOB DIDN'T CALL. The first time I called, Billy answered and told me that Jacob was still in bed. I got nosy, checking to make sure that Billy had taken him to a doctor. Billy said he had, but, for some reason I couldn't nail down, I didn't really believe him. I called again, several times a day, for the next two days, but no one was ever there. Saturday, I decided to go see him, invitation be damned. But the little red house was empty. This frightened mewas Jacob so sick that he'd needed to go to the hospital? I stopped by the hospital on the way back home, but the nurse at the front desk told me neither Jacob or Billy had been in. I made Charlie call Harry Clearwater as soon as he got home from work. I waited, anxious, while Charlie chatted with his old friend; the conversation seemed to go on forever without Jacob even being mentioned. It seemed that Harry had been in the hospital . . some kind of tests for his heart. Charlie's forehead got all pinched together, but Harry joked with him, blowing it off, until Charlie was laughing again. Only then did Charlie ask about Jacob, and now his side of the conversation didn't give me much to work with, just a lot of hmms and yeahs. I drummed my fingers against the counter beside him until he put a hand over mine to stop me. Finally, Charlie hung up the phone and turned to me. â€Å"Harry says there's been some trouble with the phone lines, and that's why you haven't been able to get through. Billy took Jake to the doc down there, and it looks like he has mono. He's real tired, and Billy said no visitors,† he reported. â€Å"No visitors?† I demanded in disbelief. Charlie raised one eyebrow. â€Å"Now don't you go making a pest of yourself, Bells. Billy knows what's best for Jake. He'll be up and around soon enough. Be patient.† I didn't push it. Charlie was too worried about Harry. That was clearly the more important issueit wouldn't be right to bug him with my lesser concerns. Instead, I went straight upstairs and turned on my computer. I found a medical site online and typed â€Å"mononucleosis† into the search box. All I knew about mono was that you were supposed to get it from kissing, which was clearly not the case with Jake. I read through the symptoms quicklythe fever he definitely had, but what about the rest of it? No horrible sore throat, no exhaustion, no headaches, at least not before he'd gone home from the movie; he'd said he felt â€Å"fit as a fiddle.† Did it really come on so fast? The article made it sound like the sore stuff showed up first. I glared at the computer screen and wondered why, exactly, I was doing this. Why did I feel so so suspicious, like I didn't believe Billy's story? Why would Billy lie to Harry? I was being silly, probably. I was just worried, and, to be honest, I was afraid of not being allowed to see Jacobthat made me nervous. I skimmed through the rest of the article, looking for more information. I stopped when I got to the part about how mono could last more than a month. A month? My mouth fell open. But Billy couldn't enforce the no-visitors thing that long. Of course not. Jake would go crazy stuck in bed that long without anyone to talk to. What was Billy afraid of, anyway? The article said that a person with mono needed to avoid physical activity, but there was nothing about visitors. The disease wasn't very infectious. I'd give Billy a week, I decided, before I got pushy. A week was generous. A week was long. By Wednesday, I was sure I wasn't going to live till Saturday. When I'd decided to leave Billy and Jacob alone for a week, I hadn't really believed that Jacob would go along with Billy's rule. Every day when I got home from school, I ran to the phone to check for messages. There never were any. I cheated three times by trying to call him, but the phone lines still weren't working. I was in the house much too much, and much too alone. Without Jacob, and my adrenaline and my distractions, everything I'd been repressing started creeping up on me. The dreams got hard again. I could no longer see the end coming. Just the horrible nothingnesshalf the time in the forest, half the time in the empty fern sea where the white house no longer existed. Sometimes Sam Uley was there in the forest, watching me again. I paid him no attentionthere was no comfort in his presence; it made me feel no less alone. It didn't stop me from screaming myself awake, night after night. The hole in my chest was worse than ever. I'd thought that I'd been getting it under control, but I found myself hunched over, day after day, clutching my sides together and gasping for air. I wasn't handling alone well. I was relieved beyond measure the morning I woke upscreaming, of courseand remembered that it was Saturday. Today I could call Jacob. And if the phone lines still weren't working, then I was going to La Push. One way or another, today would be better than the last lonely week. I dialed, and then waited without high expectations. It caught me off guard when Billy answered on the second ring. â€Å"Hello?† â€Å"Oh, hey, the phone is working again! Hi, Billy. It's Bella. I was just calling to see how Jacob is doing. Is he up for visitors yet? I was thinking about dropping by† â€Å"I'm sorry, Bella,† Billy interrupted, and I wondered if he were watching TV; he sounded distracted. â€Å"He's not in.† â€Å"Oh.† It took me a second. â€Å"So he's feeling better then?† â€Å"Yeah,† Billy hesitated for an instant too long. â€Å"Turns out it wasn't mono after all. Just some other virus.† â€Å"Oh. So where is he?† â€Å"He's giving some friends a ride up to Port AngelesI think they were going to catch a double feature or something. He's gone for the whole day.† â€Å"Well, that's a relief. I've been so worried. I'm glad he felt good enough to get out.† My voice sounded horribly phony as I babbled on. Jacob was better, but not well enough to call me. He was out with friends. I was sitting home, missing him more every hour. I was lonely, worried, bored perforatedand now also desolate as I realized that the week apart had not had the same effect on him. â€Å"Is there anything in particular you wanted?† Billy asked politely. â€Å"No, not really.† â€Å"Well, I'll tell him that you called,† Billy promised. â€Å"Bye, Bella.† â€Å"Bye,† I replied, but he'd already hung up. I stood for a moment with the phone still in my hand. Jacob must have changed his mind, just like I'd feared. He was going to take my advice and not waste any more time on someone who couldn't return his feelings. I felt the blood run out of my face. â€Å"Something wrong?† Charlie asked as he came down the stairs. â€Å"No,† I lied, hanging up the phone. â€Å"Billy says Jacob is feeling better. It wasn't mono. So that's good.† â€Å"Is he coming here, or are you going there?† Charlie asked absentmindedly as he started poking through the fridge. â€Å"Neither,† I admitted. â€Å"He's going out with some other friends.† The tone of my voice finally caught Charlie's attention. He looked up at me with sudden alarm, his hands frozen around a package of cheese slices. â€Å"Isn't it a little early for lunch?† I asked as lightly as I could manage, trying to distract him. â€Å"No, I'm just packing something to take out to the river† â€Å"Oh, fishing today?† â€Å"Well, Harry called and it's not raining.† He was creating a stack of food on the counter as he spoke. Suddenly he looked up again as if he'd just realized something. â€Å"Say, did you want me to stay with you, since Jake's out?† â€Å"That's okay, Dad,† I said, working to sound indifferent. â€Å"The fish bite better when the weather's nice.† He stared at me, indecision clear on his face. I knew that he was worrying, afraid to leave me alone, in case I got â€Å"mopey† again. â€Å"Seriously, Dad. I think I'll call Jessica,† I fibbed quickly. I'd rather be alone than have him watching me all day. â€Å"We have a Calculus test to study for. I could use her help.† That part was true. But I'd have to make do without it. â€Å"That's a good idea. You've been spending so much time with Jacob, your other friends are going to think you've forgotten them.† I smiled and nodded as if I cared what my other friends thought. Charlie started to turn, but then spun back with a worried expression. â€Å"Hey, you'll study here or at Jess's, right?† â€Å"Sure, where else?† â€Å"Well, it's just that I want you to be careful to stay out of the woods, like I told you before.† It took me a minute to understand, distracted as I was. â€Å"More bear trouble?† Charlie nodded, frowning. â€Å"We've got a missing hikerthe rangers found his camp early this morning, but no sign of him. There were some really big animal prints of course those could have come later, smelling the food Anyway, they're setting traps for it now.† â€Å"Oh,† I said vaguely. I wasn't really listening to his warnings; I was much more upset by the situation with Jacob than by the possibility of being eaten by a bear. I was glad that Charlie was in a hurry. He didn't wait for me to call Jessica, so I didn't have to put on that charade. I went through the motions of gathering my school-books on the kitchen table to pack them in my bag; that was probably too much, and if he hadn't been eager to hit the holes, it might have made him suspicious. I was so busy looking busy that the ferociously empty day ahead didn't really crash down on me until after I'd watched him drive away. It only took about two minutes of staring at the silent kitchen phone to decide that I wasn't staying home today. I considered my options. I wasn't going to call Jessica. As far as I could tell, Jessica had crossed over to the dark side. I could drive to La Push and get my motorcyclean appealing thought but for one minor problem: who was going to drive me to the emergency room if I needed it afterward? Or I already had our map and compass in the truck. I was pretty sure I understood the process well enough by now that I wouldn't get lost. Maybe I could eliminate two lines today, putting us ahead of schedule for whenever Jacob decided to honor me with his presence again. I refused to think about how long that might be. Or if it was going to be never. I felt a brief twinge of guilt as I realized how Charlie would feel about this, but I ignored it. I just couldn't stay in the house again today. A few minutes later I was on the familiar dirt road that led to nowhere in particular. I had the windows rolled down and I drove as fast as was healthy for my truck, trying to enjoy the wind against my face. It was cloudy, but almost drya very nice day, for Forks. Getting started took me longer than it would have taken Jacob. After I parked in the usual spot, I had to spend a good fifteen minutes studying the little needle on the compass face and the markings on the now worn map. When I was reasonably certain that I was following the right line of the web, I set off into the woods. The forest was full of life today, all the little creatures enjoying the momentary dryness. Somehow, though, even with the birds chirping and cawing, the insects buzzing noisily around my head, and the occasional scurry of the field mice through the shrubs, the forest seemed creepier today; it reminded me of my most recent nightmare. I knew it was just because I was alone, missing Jacob's carefree whistle and the sound of another pair of feet squishing across the damp ground. The sense of unease grew stronger the deeper I got into the trees. Breathing started to get more difficultnot because of exertion, but because I was having trouble with the stupid hole in my chest again. I kept my arms tight around my torso and tried to banish the ache from my thoughts. I almost turned around, but I hated to waste the effort I'd already expended. The rhythm of my footsteps started to numb my mind and my pain as I trudged on. My breathing evened out eventually, and I was glad I hadn't quit. I was getting better at this bushwhacking thing; I could tell I was faster. I didn't realize quite how much more efficiently I was moving. I thought I'd covered maybe four miles, and I wasn't even starting to look around for it yet. And then, with an abruptness that disoriented me, I stepped through a low arch made by two vine maplespushing past the chest-high fernsinto the meadow. It was the same place, of that I was instantly sure. I'd never seen another clearing so symmetrical. It was as perfectly round as if someone had intentionally created the flawless circle, tearing out the trees but leaving no evidence of that violence in the waving grass. To the east, I could hear the stream bubbling quietly. The place wasn't nearly so stunning without the sunlight, but it was still very beautiful and serene. It was the wrong season for wildflowers; the ground was thick with tall grass that swayed in the light breeze like ripples across a lake. It was the same place but it didn't hold what I had been searching for. The disappointment was nearly as instantaneous as the recognition. I sank down right where I was, kneeling there at the edge of the clearing, beginning to gasp. What was the point of going any farther? Nothing lingered here. Nothing more than the memories that I could have called back whenever I wanted to, if I was ever willing to endure the corresponding painthe pain that had me now, had me cold. There was nothing special about this place without him. I wasn't exactly sure what I'd hoped to feel here, but the meadow was empty of atmosphere, empty of everything, just like everywhere else. Just like my nightmares. My head swirled dizzily. At least I'd come alone. I felt a rush of thankfulness as I realized that. If I'd discovered the meadow with Jacob well, there was no way I could have disguised the abyss I was plunging into now. How could I have explained the way I was fracturing into pieces, the way I had to curl into a ball to keep the empty hole from tearing me apart? It was so much better that I didn't have an audience. And I wouldn't have to explain to anyone why I was in such a hurry to leave, either. Jacob would have assumed, after going to so much trouble to locate the stupid place, I would want to spend more than a few seconds here. But I was already trying to find the strength to get to my feet again, forcing myself out of the ball so that I could escape. There was too much pain in this empty place to bearI would crawl away if I had to. How lucky that I was alone! Alone. I repeated the word with grim satisfaction as I wrenched myself to my feet despite the pain. At precisely that moment, a figure stepped out from the trees to the north, some thirty paces away. A dizzying array of emotions shot through me in a second. The first was surprise; I was far from any trail here, and I didn't expect company. Then, as my eyes focused on the motionless figure, seeing the utter stillness, the pallid skin, a rush of piercing hope rocked through me. I suppressed it viciously, fighting against the equally sharp lash of agony as my eyes continued to the face beneath the black hair, the face that wasn't the one I wanted to see. Next was fear; this was not the face I grieved for, but it was close enough for me to know that the man facing me was no stray hiker. And finally, in the end, recognition. â€Å"Laurent!† I cried in surprised pleasure. It was an irrational response. I probably should have stopped at fear. Laurent had been one of James's coven when we'd first met. He hadn't been involved with the hunt that followedthe hunt where I was the quarrybut that was only because he was afraid; I was protected by a bigger coven than his own. It would have been different if that wasn't the casehe'd had no compunctions, at the time, against making a meal of me. Of course, he must have changed, because he'd gone to Alaska to live with the other civilized coven there, the other family that refused to drink human blood for ethical reasons. The other family like but I couldn't let myself think the name. Yes, fear would have made more sense, but all I felt was an overwhelming satisfaction. The meadow was a magic place again. A darker magic than I'd expected, to be sure, but magic all the same. Here was the connection I'd sought. The proof, however remote, thatsomewhere in the same world where I lived he did exist. It was impossible how exactly the same Laurent looked. I suppose it was very silly and human to expect some kind of change in the last year. But there was something I couldn't quite put my finger on it. â€Å"Bella?† he asked, looking more astonished than I felt. â€Å"You remember.† I smiled. It was ridiculous that I should be so elated because a vampire knew my name. He grinned. â€Å"I didn't expect to see you here.† He strolled toward me, his expression bemused. â€Å"Isn't it the other way around? I do live here. I thought you'd gone to Alaska.† He stopped about ten paces away, cocking his head to the side. His face was the most beautiful face I'd seen in what felt like an eternity. I studied his features with a strangely greedy sense of release. Here was someone I didn't have to pretend forsomeone who already knew everything I could never say. â€Å"You're right,† he agreed. â€Å"I did go to Alaska. Still, I didn't expect When I found the Cullen place empty, I thought they'd moved on.† â€Å"Oh.† I bit my lip as the name set the raw edges of my wound throbbing. It took me a second to compose myself. Laurent waited with curious eyes. â€Å"They did move on,† I finally managed to tell him. â€Å"Hmm,† he murmured. â€Å"I'm surprised they left you behind. Weren't you sort of a pet of theirs?† His eyes were innocent of any intended offense. I smiled wryly. â€Å"Something like that.† â€Å"Hmm,† he said, thoughtful again. At that precise moment, I realized why he looked the sametoo much the same. After Carlisle told us that Laurent had stayed with Tanya's family, I'd begun to picture him, on the rare occasions that I thought of him at all, with the same golden eyes that the CullensI forced the name out, wincinghad. That all good vampires had. I took an involuntary step back, and his curious, dark red eyes followed the movement. â€Å"Do they visit often?† he asked, still casual, but his weight shifted toward me. â€Å"Lie,† the beautiful velvet voice whispered anxiously from my memory. I started at the sound of his voice, but it should not have surprised me. Was I nor in the worst danger imaginable? The motorcycle was safe as kittens next to this. I did what the voice said to do. â€Å"Now and again.† I tried to make my voice light, relaxed. â€Å"The time seems longer to me, I imagine. You know how they get distracted† I was beginning to babble. I had to work to shut myself up. â€Å"Hmm,† he said again. â€Å"The house smelled like it had been vacant for a while† â€Å"You must lie better than that, Bella,† the voice urged. I tried. â€Å"I'll have to mention to Carlisle that you stopped by. He'll be sorry they missed your visit.† I pretended to deliberate for a second. â€Å"But I probably shouldn't mention it to Edward, I suppose† I barely managed to say his name, and it twisted my expression on the way out, ruining my bluff â€Å"he has such a temper well, I'm sure you remember. He's still touchy about the whole James thing.† I rolled my eyes and waved one hand dismissively, like it was all ancient history, but there was an edge of hysteria to my voice. I wondered if he would recognize what it was. â€Å"Is he really?† Laurent asked pleasantly skeptically. I kept my reply short, so that my voice wouldn't betray my panic. â€Å"Mm-hmm.† Laurent took a casual step to the side, gazing around at the little meadow. I didn't miss that the step brought him closer to me. In my head, the voice responded with a low snarl. â€Å"So how are things working out in Denali? Carlisle said you were staying with Tanya?† My voice was too high. The question made him pause. â€Å"I like Tanya very much,† he mused. â€Å"And her sister Irina even more I've never stayed in one place for so long before, and I enjoy the advantages, the novelty of it. But, the restrictions are difficult I'm surprised that any of them can keep it up for long.† He smiled at me conspiratorially. â€Å"Sometimes I cheat.† I couldn't swallow. My foot started to ease back, but I froze when his red eyes flickered down to catch the movement. â€Å"Oh,† I said in a faint voice. â€Å"Jasper has problems with that, too.† â€Å"Don't move,† the voice whispered. I tried to do what he instructed. It was hard; the instinct to take flight was nearly uncontrollable. â€Å"Really?† Laurent seemed interested. â€Å"Is that why they left?† â€Å"No,† I answered honestly. â€Å"Jasper is more careful at home.† â€Å"Yes,† Laurent agreed. â€Å"I am, too.† The step forward he took now was quite deliberate. â€Å"Did Victoria ever find you?† I asked, breathless, desperate to distract him. It was the first question that popped into my head, and I regretted it as soon as the words were spoken. Victoriawho had hunted me with James, and then disappearedwas not someone I wanted to think of at this particular moment. But the question did stop him. â€Å"Yes,† he said, hesitating on that step. â€Å"I actually came here as a favor to her.† He made a face. â€Å"She won't be happy about this.† â€Å"About what?† I said eagerly, inviting him to continue. He was glaring into the trees, away from me. I took advantage of his diversion, taking a furtive step back. He looked back at me and smiledthe expression made him look like a black-haired angel. â€Å"About me killing you,† he answered in a seductive purr. I staggered back another step. The frantic growling in my head made it hard to hear. â€Å"She wanted to save that part for herself,† he went on blithely. â€Å"She's sort of put out with you, Bella.† â€Å"Me?† I squeaked. He shook his head and chuckled. â€Å"I know, it seems a little backward to me, too. But James was her mate, and your Edward killed him.† Even here, on the point of death, his name tore against my unhealed wounds like a serrated edge. Laurent was oblivious to my reaction. â€Å"She thought it more appropriate to kill you than Edwardfair turnabout, mate for mate. She asked me to get the lay of the land for her, so to speak. I didn't imagine you would be so easy to get to. So maybe her plan was flawedapparently it wouldn't be the revenge she imagined, since you must not mean very much to him if he left you here unprotected.† Another blow, another tear through my chest. Laurent's weight shifted slightly, and I stumbled another step back. He frowned. â€Å"I suppose she'll be angry, all the same.† â€Å"Then why not wait for her?† I choked out. A mischievous grin rearranged his features. â€Å"Well, you've caught me at a bad time, Bella. I didn't come to this place on Victoria's missionI was hunting. I'm quite thirsty, and you do smell simply mouthwatering.† Laurent looked at me with approval, as if he meant it as a compliment. â€Å"Threaten him,† the beautiful delusion ordered, his voice distorted with dread. â€Å"He'll know it was you,† I whispered obediently. â€Å"You won't get away with this.† â€Å"And why not?† Laurent's smile widened. He gazed around the small opening in the trees. â€Å"The scent will wash away with the next rain. No one will find your bodyyou'll simply go missing, like so many, many other humans. There's no reason for Edward to think of me, if he cares enough to investigate. This is nothing personal, let me assure you, Bella. Just thirst.† â€Å"Beg,† my hallucination begged. â€Å"Please,† I gasped. Laurent shook his head, his face kind. â€Å"Look at it this way, Bella. You're very lucky I was the one to find you.† â€Å"Am I?† I mouthed, faltering another step back. Laurent followed, lithe and graceful. â€Å"Yes,† he assured me. â€Å"I'll be very quick. You won't feel a thing, I promise. Oh, I'll lie to Victoria about that later, naturally, just to placate her. But if you knew what she had planned for you, Bella† He shook his head with a slow movement, almost as if in disgust. â€Å"I swear you'd be thanking me for this.† I stared at him in horror. He sniffed at the breeze that blew threads of my hair in his direction. â€Å"Mouthwatering,† he repeated, inhaling deeply. I tensed for the spring, my eyes squinting as I cringed away, and the sound of Edward's furious roar echoed distantly in the back of my head. His name burst through all the walls I'd built to contain it. Edward, Edward, Edward. I was going to die. It shouldn't matter if I thought of him now. Edward, I love you. Through my narrowed eyes, I watched as Laurent paused in the act of inhaling and whipped his head abruptly to the left. I was afraid to look away from him, to follow his glance, though he hardly needed a distraction or any other trick to overpower me. I was too amazed to feel relief when he started slowly backing away from me. â€Å"I don't believe it,† he said, his voice so low that I barely heard it. I had to look then. My eyes scanned the meadow, searching for the interruption that had extended my life by a few seconds. At first I saw nothing, and my gaze flickered back to Laurent. He was retreating more quickly now, his eyes boring into the forest. Then I saw it; a huge black shape eased out of the trees, quiet as a shadow, and stalked deliberately toward the vampire. It was enormousas tall as a horse, but thicker, much more muscular. The long muzzle grimaced, revealing a line of dagger-like incisors. A grisly snarl rolled out from between the teeth, rumbling across the clearing like a prolonged crack of thunder. The bear. Only, it wasn't a bear at all. Still, this gigantic black monster had to be the creature causing all the alarm. From a distance, anyone would assume it was a bear. What else could be so vast, so powerfully built? I wished I were lucky enough to see it from a distance. Instead, it padded silently through the grass a mere ten feet from where I stood. â€Å"Don't move an inch,† Edward's voice whispered. I stared at the monstrous creature, my mind boggling as I tried to put a name to it. There was a distinctly canine cast to the shape of it, the way it moved. I could only think of one possibility, locked in horror as I was. Yet I'd never imagined that a wolf could get so big. Another growl rumbled in its throat, and I shuddered away from the sound. Laurent was backing toward the edge of the trees, and, under the freezing terror, confusion swept through me. Why was Laurent retreating? Granted, the wolf was monstrous in size, but it was just an animal. What reason would a vampire have for fearing an animal? And Laurent was afraid. His eyes were wide with horror, just like mine. As if in answer to my question, suddenly the mammoth wolf was not alone. Flanking it on either side, another two gigantic beasts prowled silently into the meadow. One was a deep gray, the other brown, neither one quite as tall as the first. The gray wolf came through the trees only a few feet from me, its eyes locked on Laurent. Before I could even react, two more wolves followed, lined up in a V, like geese flying south. Which meant that the rusty brown monster that shrugged through the brush last was close enough for me to touch. I gave an involuntary gasp and jumped backwhich was the stupidest thing I could have done. I froze again, waiting for the wolves to turn on me, the much weaker of the available prey. I wished briefly that Laurent would get on with it and crush the wolf packit should be so simple for him. I guessed that, between the two choices before me, being eaten by wolves was almost certainly the worse option. The wolf closest to me, the reddish brown one, turned its head slightly at the sound of my gasp. The wolf's eyes were dark, nearly black. It gazed at me for a fraction of a second, the deep eyes seeming too intelligent for a wild animal. As it stared at me, I suddenly thought of Jacobagain, with gratitude. At least I'd come here alone, to this fairytale meadow filled with dark monsters. At least Jacob wasn't going to die, too. At least I wouldn't have his death on my hands. Then another low growl from the leader caused the russet wolf to whip his head around, back toward Laurent. Laurent was staring at the pack of monster wolves with unconcealed shock and fear. The first I could understand. But I was stunned when, without warning, he spun and disappeared into the trees. He ran away. The wolves were after him in a second, sprinting across the open grass with a few powerful bounds, snarling and snapping so loudly that my hands flew up instinctively to cover my ears. The sound faded with surprising swiftness once they disappeared into the woods. And then I was alone again. My knees buckled under me, and I fell onto my hands, sobs building in my throat. I knew I needed to leave, and leave now. How long would the wolves chase Laurent before they doubled back for me? Or would Laurent turn on them? Would he be the one that came looking? I couldn't move at first, though; my arms and legs were shaking, and I didn't know how to get back to my feet. My mind couldn't move past the fear, the horror or the confusion. I didn't understand what I'd just witnessed. A vampire should not have run from overgrown dogs like that. What good would their teeth be against his granite skin? And the wolves should have given Laurent a wide berth. Even if their extraordinary size had taught them to fear nothing, it still made no sense that they would pursue him. I doubted his icy marble skin would smell anything like food. Why would they pass up something warmblooded and weak like me to chase after Laurent? I couldn't make it add up. A cold breeze whipped through the meadow, swaying the grass like something was moving through it. I scrambled to my feet, backing away even though the wind brushed harmlessly past me. Stumbling in panic, I turned and ran headlong into the trees. The next few hours were agony. It took me three times as long to escape the trees as it had to get to the meadow. At first I paid no attention to where I was headed, focused only on what I was running from By the time I collected myself enough to remember the compass, I was deep in the unfamiliar and menacing forest. My hands were shaking so violently that I had to set the compass on the muddy ground to be able to read it. Every few minutes I would stop to put the compass dowr and check that I was still heading northwest, hearingwhen the sounds weren't hidden behind the frantic squelching of my footstepsthe quiet whisper of unseen things moving in the leaves. The call of a jaybird made me leap back and fall into a thick stand of young spruce, scraping up my arms and tangling my hair with sap. The sudden rush of a squirrel up a hemlock made me scream so loud it hurt my own ears. At last there was a break in the trees ahead. I came out onto the empty road a mile or so south of where I'd left the truck. Exhausted as I was, I jogged up the lane until I found it. By the time I pulled myself into the cab, I was sobbing again. I fiercely shoved down both stiff locks before I dug my keys out of my pocket. The roar of the engine was comforting and sane. It helped me control the tears as I sped as fast as my truck would allow toward the main highway. I was calmer, but still a mess when I got home. Charlie's cruiser was in the drivewayI hadn't realized how late it was. The sky was already dusky. â€Å"Bella?† Charlie asked when I slammed the front door behind me and hastily turned the locks. â€Å"Yeah, it's me.† My voice was unsteady. â€Å"Where have you been?† he thundered, appearing through the kitchen doorway with an ominous expression. I hesitated. He'd probably called the Stanleys. I'd better stick to the truth. â€Å"I was hiking,† I admitted. His eyes were tight. â€Å"What happened to going to Jessica's?† â€Å"I didn't feel like Calculus today.† Charlie folded his arms across his chest. â€Å"I thought I asked you to stay out of the forest.† â€Å"Yeah, I know. Don't worry, I won't do it again.† I shuddered. Charlie seemed to really look at me for the first time. I remembered that I had spent some time on the forest floor today; I must be a mess. â€Å"What happened?† Charlie demanded. Again, I decided that the truth, or part of it anyway, was the best option. I was too shaken to pretend that I'd spent an uneventful day with the flora and fauna. â€Å"I saw the bear.† I tried to say it calmly, but my voice was high and shaky. â€Å"It's not a bear, thoughit's some kind of wolf. And there are five of them. A big black one, and gray, and reddish-brown† Charlie's eyes grew round with horror. He strode quickly to me and grabbed the tops of my arms. â€Å"Are you okay?† My head bobbed in a weak nod. â€Å"Tell me what happened.† â€Å"They didn't pay any attention to me. But aftet they were gone, I ran away and I fell down a lot.† He let go of my shoulders and wrapped his arms around me. For a long moment, he didn't say anything. â€Å"Wolves,† he murmured. â€Å"What?† â€Å"The rangers said the tracks were wrong for a bearbut wolves just don't get that big† â€Å"These were huge.† â€Å"How many did you say you saw?† â€Å"Five.† Charlie shook his head, frowning with anxiety, He finally spoke in a tone that allowed no argument. â€Å"No morehiking.† â€Å"No problem,† I promised fervently. Charlie called the station to report what I'd seen. I fudged a little bit about where exactly I'd seen the wolvesclaiming I'd been on the trail that led to the north. I didn't want my dad to know how deep I'd gone into the forest against his wishes, and, more importantly, I didn't want anyone wandering near where Laurent might be searching for me. The thought of it made me feel sick. â€Å"Are you hungry?† he asked me when he hung up the phone. I shook my head, though I must have been starving. I hadn't eaten all day. â€Å"Just tired,† I told him. I turned for the stairs. â€Å"Hey,† Charlie said, his voice suddenly suspicious again. â€Å"Didn't you say Jacob was gone for the day?† â€Å"That's what Billy said,† I told him, confused by his question. He studied my expression for a minute, and seemed satisfied with what he saw there. â€Å"Huh.† â€Å"Why?† I demanded. It sounded like he was implying that I'd been lying to him this morning. About something besides studying with Jessica. â€Å"Well, it's just that when I went to pick up Harry, I saw Jacob out in front of the store down there with some of his friends. I waved hi, but he well, I guess I don't know if he saw me. I think maybe he was arguing with his friends. He looked strange, like he was upset about something. And different. It's like you can watch that kid growing! He gets bigger every time I see him.† â€Å"Billy said Jake and his friends were going up to Port Angeles to see some movies. They were probably just waiting for someone to meet them.† â€Å"Oh.† Charlie nodded and headed for the kitchen. I stood in the hall, thinking about Jacob arguing with his friends. I wondered if he had confronted Embry about the situation with Sam. Maybe that was the reason he'd ditched me todayif it meant he could sort things out with Embry, I was glad he had. I paused to check the locks again before I went to my room. It was a silly thing to do. What difference would a lock make to any of the monsters I'd seen this afternoon? I assumed the handle alone would stymie the wolves, not having opposable thumbs. And if Laurent came here Or Victoria. I lay down on my bed, but I was shaking too hard to hope for sleep. I curled into a cramped ball under my quilt, and faced the horrifying facts. There was nothing I could do. There were no precautions I could take. There was no place I could hide. There was no one who could help me. I realized, with a nauseous roll of my stomach, that the situation was worse than even that. Because all those facts applied to Charlie, too. My father, sleeping one room away from me, was just a hairsbreadth off the heart of the target that was centered on me. My scent would lead them here, whether I was here or not. The tremors rocked me until my teeth chattered. To calm myself, I fantasized the impossible: I imagined the big wolves catching up to Laurent in the woods and massacring the indestructible immortal the way they would any normal person. Despite the absurdity of such a vision, the idea comforted me. If the wolves got him, then he couldn't tell Victoria I was here all alone. If he didn't return, maybe she'd think the Cullens were still protecting me. If only the wolves could win such a fight My good vampires were never coming back; how soothing it was to imagine that the other kind could also disappear. I squeezed my eyes tight together and waited for unconsciousnessalmost eager for my nightmare to start. Better that than the pale, beautiful face that smiled at me now from behind my lids. In my imagination, Victoria's eyes were black with thirst, bright with anticipation, and her lips curled back from her gleaming teeth in pleasure. Her red hair was brilliant as fire; it blew chaotically around her wild face. Laurent's words repeated in my head. If you knew what she had planned for you I pressed my fist against my mouth to keep from screaming.

MRI Contrast Agents

â€Å"MRI contrast is used for a variety of reasons.   Primarily, it is used to improve the detection of disease; that is, to increase sensitivity and diagnostic confidence, to enhance the ability to differentiate normal and abnormal tissue; and to identify the extent of the disease† (Muroff, 2001).Contrast agents are chemical substances used in anatomical or functional imaging for the purpose of increasing visual differences between normal and abnormal tissue.   These chemical substances are used to alter relaxation times.   Contrast agents are classified by changes in relaxation times after injection.There are six main categories of MRI contrast agents: Gastrointestinal, Intravenous, Intravascular (blood pool), Tumor-specific, and Reticuloendothelial contrast agents.Within the Gastrointestinal contrast agent category, there two subcategories: Positive and Negative contrast agents.Positive contrast agents cause a reduction in T1 relaxation times.   These agents appear brightly on images.   They may contain Manganese, Iron or Gadolinium as active elements.Positive contrast agents have three classifications: Paramagnetic agents, short T1-relaxation agents, and a combination of the two.Paramagnetic contrast agents have magnetic centers which create magnetic fields.   These fields interact with water protons, and have a larger effect on relaxation rates.   They include ferric chloride and gadolinium, which cause T1 and T2 shortening.   In low concentrations, T1 shortening holds the domination of the intensity of the signal.   In high concentrations, T2 shortening causes the signal to decrease.   At mid-level concentration, T1 and T2 shortening show an increase in the signal on T1 weighted images, and decreased the signal on T2 weighted images.Short T1-relaxation agents include mineral oil and oil emulsions.   In these agents, protons relax faster than protons in water, which results in short T1 time.   In bowels with T1 weighted imag es, a bright signal is apparent.Combinations include emulsion oil that contains corn oil and ferric ammonium citrate, and an emusion containing baby formula with ferrous sulfate.   Combination contrast agents distribute evenly through the bowels.Negative contrast agents will appear largely dark on images.   They are frequently called superparamagnetic iron oxide (SPIO).   They have shorter T1 and T2 relaxation times.Negative contrast agents have three classifications: diamagnetic agents, superparamagnetic agents, and perfluorochemicals.One readily available diamagnetic contrast agent is barium sulfate suspension.   It reduces the loss of bowel signals, resulting in improved pancreatic visualization.Superparamagnetic contrast agents are generally administered orally.   They include magnelite albumin microspheres and superparamagnetic iron oxide.   A large loss of the signal in the stomach and small bowels that give immense visualization of the pancreas and anterior renal margins.   This contrast agent type â€Å"accumulates in the reticuloendothelial system of the liver, and darkens healthy liver tissue in T2-weighted images† (mr-tip.com).Perfluorochemicals are organic compounds that replace protons with fluorine.   They are a special group of negative contrast agents that appear completely dark on images, because they do not contain hydrogen atoms, which are responsible for the signal in MRIs.   In gastrointestinal imaging, the purpose of perfluorochemicals is to give a complete signal absence in the bowels.Intravenous contrast agents include both ionic and nonionic chelates.   When using paramagnetic metal ions as contrast agents, there is a high level of toxicity in the doses required for imaging.   Chelates reduce the chances of long term toxicity by reducing the toxic levels.Intravascular contrast agents remain in the blood longer than most other contrast agents.   They are highly useful in diagnosis imaging that may require longer imaging times.Tumor-Specific contrast agents are targeted to tumors.   There are four main types of tumor-specific agents:Metalloporphyrins target multiple types of tumors, such as melanomas and lymphomas.Monoclonal antibodies are for specific tumors such as colon carcinomas.Ferrioxamine is a paramagnetic agent used for the kidneys and urinary tract.Nitroxides are also paramagnetic agents, but are not widely used.Reticuloendothelial contrast agents are used in liver, spleen and lymph node MRIs.   In liver and spleen imaging, specific contrast agents are used that target the reticuloendothelial system of the liver and spleen.   Because of the inability of most imagers to differentiate between normal and abnormal lymph nodes, USPIO has become widely used.   USPIO allows imagers to have the ability to differentiate between lymph nodes.â€Å"In cases where it is difficult to differentiate two types of tissue, because the signal intensity they produce is so similar, the s olution is to add a contrast agent to one of them in order to distinguish it from the other tissue† (GE Healthcare, 2007).   MRI contrast agents affect hydrogen atoms and the time they take to return to their original state, thereby increasing the signal intensity differences between the tissue with the contrast agent and the tissue without the contrast agent.   This results in an increase of contrasts on the image.ReferencesGE Healthcare (accessed January 13, 2007) www.amershamhealth.com/public/medical/mri_3.shtmlMedline Plus (revised March 2000) http://mplus.nlm.nih.gov/medlineplus/druginfo/uspdi/202770.htmlMR-Technology (accessed January 13, 2007) www.mr-tip.comMuroff, Lawrence R. (Aug. 2001) â€Å"MRI Contrast: Current Agents and Issues† Applied Radiology Online (vol. 30, No. 8) www.appliedradiology.comRunge, Val M. (Aug. 2001) â€Å"The Safety of MR Contrast Media: A Literature Review† Applied Radiology Online (Vol. 30, No. 8) www.appliedradiology.com

Mount Everest And The Sherpa s - 1359 Words

The Mount Everest and The Sherpa’s Many have dreamed of ascending it, but few have reached the top. Located in the Maha longer mountain range on the border of Nepal and Tibet. The British first surveyed Mount Everest in 1856; however, the first successful ascent wasn t until 1953 by New Zeeland s Sir Edmund Hillary and Nepal s Tenzing Norgay. Originally known as Peak 15, it was name Everest in 1865 after good surveyor Sir George. Everest is also known as Como LAN GMA means goddess mother of snow in Tibet and Sagarmatha meaning mother of the universe in Nepal. Mount Everest is officially the world tallest mountain with a peak of 29000 29 ft. Above sea level. It s bigger than 21 Empire State Building stacked on top of each other. Everest is so high; the top reaches into the earth s Stratosphere and crazily enough. It s only getting taller shifting tectonic plates cause ever to rise about one-third of an inch per year. Mount Everest is the most grueling, exhausting, and dangerous peak on the planate. Climbing Mount Everest is not an easy job. On the mountain climbers are losing at winds of up to 200 miles per hour and temperatures as cold as negative 73 degrees Celsius. The avalanches are frequent as are fallings rocks and crevices are broad and profound as the football field. Then there s the biggest danger of them all . The death spot located at 26,000 247 feet. The oxygen level in the Everest is only one-third of that sea level.Show MoreRelatedThe Commercialization Of Mount Everest Essay1512 Words   |  7 Pagescommercial ization of Mount Everest, a sad story starts to unfold. People say Everest has gone from being the definitive contest for the most capable mountaineers to a bucket list check off for quest chasers. Problems are coming forward that are threatening expeditions and livelihoods that surround Everest. 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