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ADVANCES IN MEDICINE AND BIOLOGY

ADVANCES IN MEDICINE AND BIOLOGY VOLUME 82

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ADVANCES IN MEDICINE AND BIOLOGY

ADVANCES IN MEDICINE AND BIOLOGY VOLUME 82

LEON V. BERHARDT EDITOR

New York


Copyright © 2015 by Nova Science Publishers, Inc.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: [email protected] NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers‘ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book.

Library of Congress Cataloging-in-Publication Data

ISSN: 2157-5398 ISBN: (eBook)

Published by Nova Science Publishers, Inc. † New York


Contents Preface

vii

Chapter 1

Opportunistic Eye Infections in Transplant Patients Michael W. Stewart, M.D.

Chapter 2

Clinical Manifestations of Acute Baclofen Toxicity in Adults Leslie Tamura, Frank K. Jackson, D.O., Dan Quan, D.O. and Richard W. Carlson, M.D., Ph.D.

Chapter 3

A Model of Information System for Healthcare: Global Vision and Integrated Data Flows David Rojas and Javier Carnicero

Chapter 4

An Overview of Eye-Related Photophobia R. A. Armstrong

Chapter 5

Advances in Apical Microsurgery: Technique, Materials and Prognosis Mariane M. Azuma, Pedro F. E. Bernabé, Diego Valentim, João E. Gomes-Filho, Eloi Dezan-Júnior, Gustavo Sivieri-Araujo, Rogério C. Jacinto and Luciano T. A. Cintra

1 21

39 69

89

Chapter 6

Treatment of Implant Surfaces: Insights, Outcomes and Limitations Cássia Bellotto Corrêa, Ana Lúcia Roselino Ribeiro, Lívia Alves Corrêa Moretti, Alberto Consolaro and Elcio Marcantonio Junior

115

Chapter 7

Gamma Knife Radiosurgery for GH-Producing Adenomas Yoshiyasu Iwai, M.D. and Kenichi Ishibashi, M.D.

135

Chapter 8

Dental Considerations for Acromegaly: A Review Katsuaki Mishima, DDS, Ph.D. and Yoshiya Ueyama, DDS, Ph.D.

149


vi

Contents

Chapter 9

Fungal Vaccines: State of the Art Laura E. Castrillón Rivera and Alejandro Palma Ramos

Chapter 10

Assessment of the Substandard Drugs in Developing Countries: The Impact of the Pharmaceutical Regulations on the Quality of Medicines on the Sudanese Market Importers‘ Perspective Abdeen M. Omer and Gamal K. M. Ali

Chapter 11

Intestinal Colic: A Review Elroy Patrick Weledji

Chapter 12

Infectious Agents and Autoimmunity in Acute Coronary Atherothrombosis Ivana Burazor and Aristo Vojdani

Index

159

181 199

217 225


Preface This continuing series gathers and presents original research results on the leading edge of medicine and biology. Each article has been carefully selected in an attempt to present substantial topical data across a broad spectrum. Topics discussed in this book include opportunistic eye infections in transplant patients; clinical manifestations of acute baclofen toxicity in adults; a model information system for healthcare systems; an overview of eyerelated photophobia; advances in apical microsurgery; treatment of implant surfaces; gamma knife radiosurgery for GH-producing adenomas; dental considerations for acromegaly; fungal vaccines; an assessment of the substandard drugs in developing countries; intestinal colic; and infectious agents and autoimmunity in acute coronary atherothrombosis. Chapter 1 - Transplantation of bone marrow and solid organs are highly successful, complex procedures that require life-long immunomodulation to prevention rejection of the graft. Unfortunately, prolonged pharmacologic immunosuppression subjects the patient to life and sight-threatening infections by opportunistic organisms. During the early posttransplantation period, patients are at risk of fungal infections (candida, aspergillus, and scedosporium) but after 6 months, infections due to herpes viruses (herpes simplex, herpes zoster, and cytomegalovirus) and toxoplasma become more common. Most infections can be diagnosed clinically, but cultures of intraocular fluids and biopsies of the retina and choroid provide valuable information when the diagnoses are in doubt. Prompt treatment with intraocular and systemic anti-microbial medications is important to minimize vision loss and prevent mortality. Despite rapid diagnoses and appropriate treatment of ophthalmic infections, organisms such as scedosporium often become widely disseminated and frequently cause death. Universal prophylaxis during the early post-transplant period and targeted prophylaxis for patients at high risk decreases the incidence of infections. Guidelines for ophthalmic screening examinations are not well established, but since some infections can be diagnosed before becoming symptomatic, periodic examination of high risk patients may prevent unnecessary loss of vision. Chapter 2 - Baclofen has become one of the most widely used antispastic medications. Although effective at therapeutic doses, baclofen toxicity is a continuum of tolerable side effects, overdose, tolerance, and withdrawal. A GABAB agonist, baclofen inhibits synaptic reflexes at the spinal cord level. Baclofen improves spasticity associated with spinal cord lesions, multiple sclerosis and other neurologic disorders, and has been used off-label for intractable hiccups, bladder spasticity, trigeminal neuralgia, and gastroesophageal reflux disease. The drug is absorbed completely from the gastrointestinal tract with peak serum


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concentrations reached in approximately two hours. Baclofen is eliminated predominantly (85%) by the kidneys. Renal insufficiency delays clearance of baclofen, and limited case reports have detailed increased complications in patients with renal insufficiency. Complications can also occur from dosing errors or device-related problems (e.g., leakage, catheter fracture, disconnection, occlusion, infection). Baclofen‘s dose-related adverse effects reflect its CNS inhibitory properties: Somnolence, CNS depression, respiratory depression, hypotension, cardiac conduction abnormalities, seizures, and thermoregulation disturbances. Some studies have reported cases of rhabdomyolysis, coma, and death. There are few multicenter reviews of baclofen toxicity, and case reports of baclofen overdose may have been affected by patient‘s age, comorbidities, concomitant use of another CNS depressant, and renal impairment. Oral baclofen overdose complications have occurred with doses greater than 60mg/day, with most doses greater than 200mg requiring critical care management. Baclofen withdrawal symptoms have also been reported, including: Hallucinations, seizures, hyperthermia, rhabdomyolysis, and status epilepticus. These complications are often transient or reversible. Although there is no baclofen antagonist, patients who have overdosed on baclofen often respond quickly to symptomatic care that may include: Atropine for bradycardia, vasodilators for hypertension, and phenytoin or diazepam for seizure control. Acute overdose, however, often requires additional critical care management with airway management that may include endotracheal intubation and mechanical ventilation, electrolyte repletion, and deep vein thrombosis (DVT) precautions, neurologic monitoring, thermoregulation, and restraints. Patients with renal insufficiency may require hemodialysis, which is an effective mechanism to reduce toxic drug levels. For those with intrathecal baclofen overdose, CSF drainage and subsequent cautious baclofen replacement may be necessary to treat withdrawal. As serum levels are not always available, baclofen toxicity is primarily a clinical diagnosis. Further studies are needed to develop improved detection and quantitation of baclofen, especially in the critical care setting. Chapter 3 - The information system is an essential instrument for the performance of a health system, since it makes it possible to record, process and consult huge amounts of data, guaranteeing their availability for several uses which go from healthcare provision to system management, stewardship and financing. Hence the healthcare information system is composed of elements of several kinds, like clinical, clinical-administrative and management applications, among others. The existing literature on health information management studies these different applications, but does not offer a global vision of the healthcare information system as a whole entity. This chapter adopts this global point of view and describes the structure and data flows within the information system, showing through several examples how the data generated during a medical consultation can be used for the patient‘s healthcare, the management of the used resources, the invoicing of the delivered service, and in the long term for results assessment, strategic planning, clinical research or education. As a consequence, the making of a healthcare information system requires a clear definition of data recording and analysis processes, and of the information exchange flows among the different applications. These chapter examines the fundamental requirements that arise: the use of master databases for the unambiguous identification of patients, professionals, facilities and resources; the adoption of organizational, semantic and technological standards; the implementation of mechanisms for information security management; the ability of adapting to changes in the needs of the health system; the


Preface

ix

availability of a basic technological infrastructure; and the existence of a specific legal framework. This theoretical treatment is finally backed up by the presentation of several national and supranational electronic health projects that are currently in development in Spain, the European Union and the United States of America. They all meet, at least partially, the requirements and features shown in this chapter, supporting the concept of the healthcare information system as a whole integrated entity presented by the authors and confirming their premises. Chapter 4 - This chapter provides an overview of the various eye-related causes of photophobia and the likely mechanisms responsible. Photophobia is the experience of discomfort affecting the eyes as a result of exposure to light. It has a variety of causes, including the result of eye or brain disease, or it can be a side effect of various drugs or laser surgery. Photophobia can also be a symptom of a more serious disorder such as meningitis and therefore, requires appropriate investigation, diagnosis, and treatment. Trauma or disease affecting several structures of the eye are a common cause of photophobia and can be associated with: (1) the ocular adnexia, such as blepharitis and blepharospasm, (2) the cornea, including abrasion, ulcerative keratitis, and corneal dystrophy, (3) problems in eye development, such as aniridia, buphthalmos, coloboma, and aphakia, (4) various eye inflammations, including uveitis, and (5) retinal disorders, such as achromatopsia, retinal detachment, and retinal dystrophy. There may be two main explanations for photophobia associated with these conditions: (1) direct stimulation of the trigeminal nerve due to damage, disease, or excessive light entering the eye and (2) overstimulation of the retina including a specific population of light-sensitive ganglion cells. Chapter 5 - Primary endodontic treatment for teeth with apical periodontitis is a generally reliable and successful procedure where the objective of treatment is to eliminate intraradicular infection. However, the prognosis of retreatment cases involving a periapical lesion may be poorer, particularly when a procedural error has occurred, which increases the difficulty to eliminate bacteria from the canal. Apical microsurgery is an important treatment modality for treating apical periodontitis (AP) that persists even performing orthograde root canal treatment. The goals of apical surgery are removal of diseased periapical tissues and sealing of apical root canal system to facilitate regeneration of hard and soft tissues, including the formation of new attachment cells. Over the years, many studies have provided extensive data regarding the prognosis of apical surgery performed using a variety of root-end filling materials and surgical techniques. According to the literature, the use of high-power illumination and magnification (microscope or endoscope), ultrasonic tips for root-end cavity preparation, micro-instruments, and mineral trioxide aggregate (MTA) for root-end filling produces significantly better results than those of traditional root-end surgery. Thus, the aim of this dissertation is to discuss the techniques and materials that can employed to increase the success rates of apical microsurgery. Chapter 6 - Enhancements in the microstructure and nanostructure of implant surfaces have been performed in order to increase the quality and quantity of bone-implant contact during the osseointegration process. The purpose of this chapter was to investigate the implant surfaces cited in the literature and/or commercially available, as well as its effects on the process of osseointegration and also discuss the influence of the implant surface on the bacterial adhesion.


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Nowadays, a variety of titanium implants surface treatments can be found on the market or are under analysis, including machined dental implants, sandblasting, acid-etching, laser ablation, plasma-spray titanium technique, plasma-spray hydroxyapatite technique, sol-gel, anodization, biomimetic coating with calcium phosphates and surfaces with incorporation of drugs. The modification of implant surfaces directly influences bacterial adhesion which in turn, is closely related to the development of peri-implantitis and lack of osseointegration. Chapter 7 - The stereotactic radiosurgery for pituitary adenoma has been became the standard adjuvant treatment for the residual and recurrent pituitary adenomas. The therapeutic goal for treating GH-producing pituitary adenomas is to restore normal growth hormone secretion dynamics, normalize serum insulin-like growth factor (IGF-1) concentrations, and shrink the pituitary mass, while maintaining normal anterior and posterior pituitary functions. The authors evaluate their treatment outcomes and review the articles of gamma knife radiosurgery (GKS) for GH-producing pituitary adenomas. Thirty patients treated with GKS (median treatment [tumor] volume: 0.8 ml; median prescribed marginal radiation dose: 20 Gy) were followed for a median of 126 months. ‗‗Disease remission‖ was defined as either nadir levels of GH < 1µ/l during an oral glucose load, or random GH levels 24 hrs unless there is special reasons for thinking it is likely to settle (adhesions settled before on conservative management with nasogastric aspiration and i/v fluids or an early post-operative obstruction (paralytic ileus) or if decision has been made not to operate for terminal malignancy. [7, 52]

6. Large Bowel Obstruction Although large bowel obstruction presents less frequently than its small bowel counterpart, it remains nonetheless, a common surgical emergency. The main causes of large bowel obstruction are malignancy, and volvulus of the sigmoid colon. The prevalence of both being subject to wide geographical variability. [14] Colorectal cancer is particularly prevalent in the west, accounting for at least 50% of large bowel obstruction. This proportion alters in Africa and Eastern Europe where sigmoid volvulus is the cause of obstruction in up to 40% of cases. [51] The most common site of large bowel obstruction is the sigmoid colon, accounting for 30% of all cases. This is not only because the sigmoid colon is a common site for colonic carcinoma and diverticular disease, but also because the lumen is relatively narrow and the faeces are firm rather than liquid. The second most common site is the splenic flexure, where the combination of a sharp kink in the colon together with luminal narrowing by the tumour and relatively firm stools leads to blockage. The features of a right-sided large bowel obstruction may be less obvious than those of left-sided colonic lesions because only a small proportion of the colon is distended. An obstruction at the ileocaecal valve will produce features of a low small bowel obstruction. A closed-loop obstruction may follow an acute-on-chronic large bowel obstruction from a distally obstructing colonic lesion. In cases where the ileocaecal valve forms one end of a


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closed loop strangulation obstruction is not a problem here but a similar problem to look for is intramural ischaemia of the caecum due to stretching causing patchy necrosis. Right iliac fossa tenderness in a patient with large bowel obstruction may indicate caecal distension and imminent perforation which is a disastrous complication of large bowel obstruction. According to the law of Laplace, (2T = PR where P is the transmural pressure, T is the wall tension and R is the radius of a sphere) tension (in this case in the wall of the colon) is proportional to the radius and is therefore higher in the caecum which is the widest point of the colon than elsewhere. Thus the caecum takes the brunt of the distension with imminent perforation if the caecal diameter is greater than 15cm. When there is distal obstruction the ileocaecal valve often becomes incompetent and both small and large bowel becomes distended. If left untreated the patient will start to vomit, but ischaemia or perforation of the bowel is unlikely. [53]

Figure 9. Closed-loop obstruction. Laplace‘s law-obstruction from a transverse colon carcinoma (a) ileocaecal valve remains open, (b) valve stopping reflux into the ileum resulting in closed loop obstruction.

Sigmoid volvulus is the commonest form of volvulus in the gastrointestinal tract. The anatomic defect is the narrow attachment of the root of the mesentery to the posterior abdominal wall and a long mesenteric axis. Predisposed by the very high fibre diet and long redundant sigmoid colon in Africans, chronic constipation and laxative abuse, psychiatric and senile disorders, the sigmoid colon rotates around its mesenteric pedicle usually more than 1800 counterclockwise resulting in partial or complete large bowel obstruction. There is a palpable tympanic mass and with the risk of ischaemia from venous obstruction. Plain X-ray shows massive sigmoid distension. Because of its high recurrence rate sigmoid colectomy is the definitive treatment as compared to sigmodoscopic decompression. [54] Obstruction from the less common caeacal volvulus is often incomplete initially but recurs without surgery, so laparotomy is advisable. [53] Less common cause of large bowel obstruction are sigmoid diverticular disease, either as a result of stricture or acute inflammation with oedema, and obstructed groin hernia. Inflammatory bowel disease is a very unusual cause of obstruction but strictures from any cause may precipate obstruction by proximal faecal impaction. Faecal impaction alone rarely causes obstruction. [53, 54]


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The advent of modern, fast multidetector CT (MDCT) scanners has changed management strategies for acute abdominal conditions including suspected large bowel obstruction (LBO) in all groups of patients especially the elderly, infirm and those on ITU/HDU. MDCT was shown to be more accurate in the diagnosis of LBO, is usually available on a 24-h basis, and in many institutions has replaced the urgent water soluble contrast enema CE in this group of patients. This also has the advantage of excluding incidental findings and in staging malignant disease. [56] The management of large bowel obstruction depends on its presentation. If intervention is not forthcoming following progressive symptoms of chronic obstruction over a period of time acute -on- chronic obstruction may supervene. In fact, as there is a complete spectrum of clinical presentation, patients may present with acute large bowel obstruction without a pre-existing history of obstructive symptoms. These acute presentations are managed as an emergency in order to prevent imminent perforation and faecal peritonitis. Following resuscitation, a water-soluble gastrograffin contrast enema x-ray may show the level of obstruction and importantly exclude a pseudo-obstruction if a CT scan is not available. [53] This is followed by an emergency colectomy and primary anastomosis for right sided lesions or left- sided segmental resection with or without (Hartmann‘s ) primary anastomosis. A chronic large bowel obstruction can be admitted electively for colonoscopic investigations prior to definitive elective surgery.[53,55] Self-expandable metal stents are now being used more widely in the management of malignant low left-sided large bowel obstruction. Table IV. Causes of Large bowel obstruction Cancer (primary or recurrent) Volvulus Diverticular disease Hernia Faecal impaction Inflammatory bowel disease Ischaemic stricture Anastomotic stricture

These stents are placed endoscopically under fluoroscopic control through the obstructing lesion and can remain in place for a prolonged period where the stent is definitive palliative treatment or alternatively can decompress the colon and after staging and a complete work-up a definitive one-stage resection and anastomosis may be possible. The stents are expensive but they appear to be cost-effective. Complications of perforation and bleeding are possible but uncommon, and it is likely this technique will be used more widely in the future. [57]

Conclusion Intestinal colic remains a common and difficult problem encountered by the abdominal surgeon. Following resuscitation a precise history may indicate the pathology and physical examination supported by basic imaging may indicate where the pathology is. These would



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determine which patient may require immediate surgery, urgent surgery, semi-elective surgery, or a trial of conservative management. Appreciation of fluid balance, acid-baseelectrolyte disturbance and the importance of pre-operative resuscitation decreases the morbidity and mortality from intestinal obstruction. Advances in minimally- invasive surgery can help minimize adhesion formation, the commonest cause of intestinal colic.

Conflict of Interests None.

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In: Advances in Medicine and Biology. Volume 82 Editor: Leon V. Berhardt

ISBN: 978-1-63463-312-3 © 2015 Nova Science Publishers, Inc.

Chapter 12

Infectious Agents and Autoimmunity in Acute Coronary Atherothrombosis Ivana Burazor1 and Aristo Vojdani2 1

Cardiology Department, Institute for Rehabilitation, Belgrade, Serbia 2 Immunosciences Lab Inc., Los Angeles, CA, US

Abstract Our understanding of the pathogenesis of the acute thrombotic complications of the atherosclerosis has burgeoned in recent years. We now understand that many acute thrombotic coronary occlusions do not necessarily result from critically stenosed sites in the arteries. This distinction between lesions versus lumen diameter challenges our traditional reliance upon coronary anatomy. Atherothrombosis is the major determinant of acute ischemic cardiovascular events, such as myocardial infarction and stroke. Thus, its understanding is essential to enable the development of targeted and more effective therapies. Although related in part to alterations in lipid metabolism, atherosclerosis is now considered a primarily immune-mediated disease. Upon searching the literature, we found that it is has been recently proposed that chronic infections can contribute to the development of atheromas either directly (endothelial injury, invasion of endothelial cells and platelet aggregation) or indirectly (production of antibodies to lipopolysaccharide, cytokines and dysfunction of the immune system). In response to infection (e.g., oral bacteria among others), the immune system jumps into action, deploying cells as well as antibodies in order to recognize and destroy the invaders. Antibodies are molecules produced by plasma cells and B cells against the ―enemy‖ – the infectious agent. However, owing to molecular mimicry or antigenic similarity between these infectious agents and human tissue structure, in a genetically susceptible individual, components of the body‘s immune system target one or more types of the person‘s own tissue, which may result in autoimmunity. Evidence indicates that infectious agents play a pivotal role in the induction of autoimmunities. The question of how infectious agents contribute to autoimmunity has continued to be of interest to clinical and basic researchers and immunologists in general.


218

Ivana Burazor and Aristo Vojdani In many cases, it is not a single infection but rather the ―burden of infections‖ from childhood that is responsible for the induction of autoimmunity. Taking together the above presented data, it appears that pathogens, through the release of toxins, seem to be capable of inducing changes in the host proteins. These can be recognized by the immune system, triggering an inflammatory process associated with the clinical manifestation of atherosclerosis – acute myocardial infarction. This and other immunopathogenic mechanisms need to be further elucidated.

Introduction Atherosclerosis is considered as the main underlying disease responsible for cardiovascular and cerebrovascular morbidity and mortality around the world. It results from multifactorial etiology, and traditional risk factors such as obesity, hyperlipidemia, diabetes, hypertension and cigarette smoking accounts only for a proportion of cases of cardiovascular diseases. Thus, although related in part to alterations in lipid metabolism, atherosclerosis is now considered a primarily immune-mediated disease. Our understanding of the pathogenesis of the acute thrombotic complications of the atherosclerosis has burgeoned in recent years. We now understand that many acute thrombotic coronary occlusions do not necessarily result from critically stenosed sites in the arteries. This distinction between lesions versus lumen diameter challenges our traditional reliance upon coronary anatomy.

Infectious Agents and Atherothrombosis For more than a century, it has been postulated that infectious agents are responsible for atherosclerotic diseases. The association between pathological substrate of acute myocardial infarction (AIM) and infection seems to be the rational one, as the processes of development of atherothrombosis involve a low-grade inflammation. Moreover, markers of inflammation, such as C-reactive protein, leukocyte count, fibrinogen and cytokines are regarded as predictors of present and future cardiovascular events and diseases [1]. Renewed interest in this topic has taken place since the late 1980s when as association between patients who had had acute myocardial infarction and the presence of Chlamydia pneumoniae antibodies were noted by Saikku and colleagues [2]. Further, there is evidence that infection with Helicobacter pylori, Cytomegalovirus and Porhyromonas gingivalis, etc. are associated with heart diseases. Upon searching the literature, we found that it is has been recently proposed that chronic infections (bacterial Helicobacter pylori, Chlamydia pneumonia and periodontitis among many others) can contribute to the development of atheromas either directly (endothelial injury, invasion of endothelial cells and platelet aggregation) or indirectly (production of antibodies to lipopolysaccharide, cytokines and dysfunction of the immune system).


Infectious Agents and Autoimmunity …

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The role of the immune system and autoimmune reactions in atherosclerosis appears to be a double edged-sword, with some of them being pro-atherogenic, while others can be antiatherogenic depending on what stage in the long-lasting process of atherosclerosis.

Oral Pathogens on the ‘Crime Sciene’ For years, dentists have noticed that certain characteristics are common to patients with periodonitis and patients with AIM [3-7]. Such reports emphasize that maintaining oral health might be more important than healthy teeth. The mouth is a portal of entry as well as the site of disease for microbial infections that affect general health status. The biological mechanisms that may explain the relationship might involve several different ways: bacteria from periodontal disease may enter the circulation and contribute directly to atherothrombotic processes, or systemic factors alter the immune-inflammatory processes involved in both periodontal and cardiovascular disease.

Chronic Exposure to Oral Pathogens and Autoimmune Reactivity in Acute Coronary Atherothrombosis. Our Findings We designed the study with purpose to investigate the potential interrelationship between chronic exposure to oral pathogens, the antibodies produced against them, and elevations in the levels of markers of immune-inflammatory response in acute, urgent, and lifesaving clinical settings in patients with acute myocardial atherothrombosis [8]. We measured the levels of antibodies against oral pathogens (Oral aerobes or facultative anaerobes (Streptococcus sanguis, Streptococcus oralis, and Peptostreptococcus anaerobius) and oral obligate anaerobes (Porphyromonas gingivalis, Prevotella intermedia, and Bacteroides forsythus) as well as antibodies against endothelial cells, beta-2 glycoprotein I, platelet glycoprotein IIb/IIIa, anticardiolipin antibodies, and inflammatory markers such as hs-CRP and interleukin 6, in blood samples of patients with myocardial infarction and compared them to the levels of the same antibodies and markers in samples from control subjects. IgG antibodies to oral anaerobes were highly present in patients with acute coronary atherothrombosis. A total of 88% of patients with cardiovascular disease had elevated antibodies above the mean of controls; RR was 1.33 (1.13 to 1.56) 95% CI. The mean OD of serum IgG antibodies to oral anaerobes tends to be higher among subjects with coronary artery disease than those without. IgG antibodies to oral aerobes were highly present in patients with acute coronary atherothrombosis. A total of 86% of patients had antibodies detectable compared to 52% of controls, RR 1.65 (1.34 to 2.02; 95% CI). The mean OD of serum IgG antibodies to oral aerobes tends to be higher among subjects with coronary artery disease than those without (0.996 ± 0.323 OD versus 0.769 ± 0.239 OD


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and P < 0.001). Subjects with acute coronary artery atherothrombosis showed very strong autoimmune response with elevation in antiendothelial cell IgG antibodies. Our results indicated that anti-beta-2 glycoprotein antibodies and anticardiolipin antibodies (aCLs) can be detected in patients with myocardial infarction. Antibodies to both oral anaerobes and aerobes showed strong and significant correlation with different parameters of autoimmunity, immunity, and inflammation.

Discussion Dental infections appear as cardiovascular risk factors in some cross-sectional studies and in follow-up studies [9]. This association is independent of the ―classic‖ coronary risk factors. In the meta-analysis of five cohort studies, an increased relative risk of CAD due to periodontal disease was reported [10]. A recent meta- analysis [11] of nine studies also yielded amodest but significant increase in a relative risk similar to the result of previous meta-analysis among individuals with periodontal disease compared to those without it. It is hypothesized that this association may be due to an underlying inflammatory response trait, which exposes an individual to a high risk for development of both periodontal disease and arteriosclerosis. Furthermore, periodontal disease which represents a chronic infection by oral bacteria that affects the supporting structures of teeth might provide a biological burden of inflammatory cytokines that promote atherosclerosis and thromboembolic events. Porhyromonas gingivalis, which is involved in periodonitis, may play a role in the pathogenesis of atherosclerosis and may directly infect vascular endothelial cells [12]. Upon colonization of the subgingival plaque, this pathogenic microorganism probably invades and lyses mucosal epithelial cells and digests a pathway to connective tissues [13]. In response to infection and inflammation, susceptible individuals may exhibit greater expression of local and systemic mediators and may thereby be at high risk for a future myocardial infarction or even stroke. The antibody response varies between individuals and immune system response to an organism can be influenced by individuals' genetic and immunological background, previous exposure to the organism and immunogenic characteristics of the antigenic challenge. Systemic exposure that originates from local infection may imply as insufficient local response to prevent systemic entry as well as factors that promote acute episodes of periodontal disease activity such as smoking. High antibody titers could represent a response to a chronic phase of infection in subjects but could also reflect the host response to an oral pathogen that confers protection of an individual without disease. The premise for this study was an assumption that an antibody response merely indicates systemic exposure to an oral organism. Increases of a systemic antibody response to organisms have also been associated with systemic inflammatory activity. Not only periodonitis but also many other lesions in oral cavity may generate inflammatory mediators, such as severe gingivitis.



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Matilla et al. incorporate several oral lesions and create Total Dental Index by summing several oral pathogens [14]. Several years later, Janket et al. investigated the role of Asymptotic Dental Score and coronary artery disease [15]. In response to infection (e.g., oral bacteria among others), the immune system jumps into action, deploying cells as well as antibodies in order to recognize and destroy the invaders. Antibodies are molecules produced by plasma cells and B cells against the ―enemy‖ – the infectious agent. However, owing to molecular mimicry or antigenic similarity between these infectious agents and human tissue structure, in a genetically susceptible individual, components of the body‘s immune system target one or more types of the person‘s own tissue, which may result in autoimmunity. Evidence indicates that infectious agents play a pivotal role in the induction of autoimmunities. The question of how infectious agents contribute to autoimmunity has continued to be of interest to clinical and basic researchers and immunologists in general. In many cases, it is not a single infection but rather the ―burden of infections‖ from childhood that is responsible for the induction of autoimmunity. It appears that pathogens, through the release of toxins, seem to be capable of inducing changes in the host proteins. These can be recognized by the immune system, triggering an inflammatory process associated with the clinical manifestation of atherosclerosis – acute myocardial infarction. Case-control studies demonstrated the association of aCLs with stroke and acute myocardial infarction [16, 17]. Also, the authors found that IgG/IgM/ IgA aCL and IgA for anti-beta-2 glycoprotein I associated with increased risk of ischemic stroke, arterial thrombosis, atherosclerotic immune process, acute myocardial infarction, and peripheral vascular diseases [16]. Although the exact mechanisms remain unknown, anti-beta-2 glycoprotein I was thought to interact with beta 2-glycoprotein I on the endothelial membrane and induce inflammatory reactions [18]. Artenjak et al. [19] reported on the correlation between aPL and cardiovascular risk in nonautoimmune settings. Taken together, these results did not demonstrate a clear association between aPL and acute cardiovascular events. Beta-2-glycoprotein I is present at high concentrations in the blood stream and is expressed by many cell populations, including endothelial cells, lymphocytes, and monocytes. It binds negatively not only charged molecules, including phospholipids, heparin, and oxLDL, but also the surface of activated platelets and the membrane of apoptotic cells [2024]. In our study population, those autoantibodies were highly present in patients with acute myocardial infarction. One should have in mind that antiendothelial cell antibodies may cause vasculitis as part of an autoimmune response. This is a heterogeneous family of antibodies. The IgG antibodies are highly present also in the blood sera of SLE patients and may mediate immunologic injury to blood vessel walls. Finally, significant elevation in the levels of IL-6, CRP and endothelial cell antibody indicates that inflammation driven by oral pathogens plays a significant role in the development of atherothrombosis [25, 26].


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Conclusion Atherothrombosis is the major determinant of acute ischemic cardiovascular events: myocardial infarction and stroke. Taking together the above presented data, it appears that oral pathogens, through the release of toxins, seem to be capable of inducing changes in the host proteins. These can be recognized by the immune system, triggering an inflammatory process associated with the clinical manifestation of atherosclerosis-acute myocardial infarction. This and other immunopathogenic mechanisms need to be further elucidated.Thus, its understanding is essential to enable the development of targeted and more effective therapies.

References [1] [2]

[3] [4] [5] [6] [7] [8]

[9] [10]

[11]

[12] [13]

Nieto, F. Infectious and atherosclerosis: new clues from an old hypothesis? Am. J. Epidemiol. 1998; 148: 937-948. Saikku, P., Leinonen, M., Mattila, K., et al. Serological evidence of an association of novel Chlamydia, TWAR, with chronic coronary heart disease: a possible trigger for acute myocardial infarction. Lancet. 1988; ii: 983-986. Rose, L., Mealey, B., Minsk, L., Cohen, W. Oral care for patients with cardiovascular disease and stroke. JADA. 2002;133: 37s-44s. Slavkin, H., Baum, B. Relationship of dental and oral pathology to systemic illness. JAMA. 2000; 284: 1215-1217. Meurman, J., Sanz, M., Janket, S. Oral health, atherosclerosis and cardiovascular disease. Crit. Rev. Oral Biol. Med. 2004; 15: 403-413. Rose, L., Mealey, B., Minsk, L., Cohen, W. Oral care for patients with cardiovascular disease and stroke. JADA. 2002; 133: 156-160. Clermont Goldschmidt, P., Creager, M., Lorsordo, D., et al. Circulation. 2005; 112: 3348-3353. Burazor, I., Vojdani, A.: Chronic exposure to oral pathogens and autoimmune reactivity in acute coronary atherothrombosis. Autoimmune Dis. 2014; 2014: 613157. doi: 10.1155/2014/613157. Genco, R., Offenbacher, S., Beck, J. Periodontal disease and cardiovascular disease. JADA. 2002; 133: 14S-22S. Danish, J. Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae and cytomegalovirus: meta-analysis of prospective studies. Am. Heart J. 1999: 138: S434-S437. Janket, S., Baird, A., Chuang, S., et al. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2003; 95: 559-569. Fong, I. Infections and their role in atherosclerotic vascular disease. JADA 2002; 133: 7S-13S. Herzberg, M., Meyer, M. Effects of oral flora on platelets: Possible consequences in cardiovascular disease. J. Periodontol. 1996; 67: 1138-1142.



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[14] Matilla, K., Nieminen, M., Valtonen, V., et al. Association between dental health and acute myocardial infarction. BMJ. 1989; 298: 779-781. [15] Janket, S., Qvarnstrom, M., Meurman, J., et al. Asymptomatic dental score and prevalent coronary heart disease. Circulation 2004; 109: 1095-1100. [16] Kivity, S., Agmon-Levin, N., Blank, M., Shoenfeld, Y. Infections and autoimmunity— friends or foes? Trends in Immunology. 2009; 30 (8): 409–414. [17] Brey, R., Abbott, R., Curb, J., et al. β2-glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu Heart Program. Stroke. 2001;32(8):1701–1706. [18] Kobayash, K., Kishi, M., Atsumi, T., et al. Circulating oxidized LDL forms complexes with â 2-glycoprotein I: implication as an atherogenic autoantigen. Journal of Lipid Research. 2003;44(4):716–726. [19] Artenjak, A., Lakota, K., Frank, M., et al. Antiphospholipid antibodies as nontraditional risk factors in atherosclerosis based cardiovascular diseases without overt autoimmunity. A critical updated review. Autoimmunity Reviews. 2012;11:873–882. [20] de Groot, P., Meijers, J. â2-glycoprotein I: evolution, structure and function. Journal of Thrombosis and Haemostasis. 2011;9(7):1275–1284. [21] Fan, J., Watanabe, T. Inflammatory reactions in the pathogenesis of atherosclerosis. Journal of Atherosclerosis and Thrombosis. 2003;10(2): 63–71 [22] Tracy, R., Lemaitre, R., Psaty, B., et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17(6):1121–1127. [23] Koenig, W., Sund, M., Fröhlich, M., et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middleaged men: results from the MONICA (monitoring trends and determinants in cardiovascular disease) Augsburg cohort study, 1984 to 1992. Circulation. 1999;99(2):237–242. [24] Pradhan, A., Manson, J., Rossouw, J., et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the women‘s health initiative observational study. Journal of the American Medical Association. 2002;288(8):980–987. [25] Vojdani, A. Antibodies as predictors of autoimmune diseases and cancer. Expert Opinion on Medical Diagnostics. 2008;2(6):593–605. [26] Lundberg, K., Wegner, N., Yucel-Lindberg, T., Venables, P. J. Periodontitis in RA-the citrullinated enolase connection. Nature Reviews Rheumatology. 2010;6(12):727–730.



Index # 10q24, 82

A abuse, 23, 35, 211 access, 28, 32, 34, 45, 46, 49, 50, 51, 53, 54, 55, 56, 57, 59, 60, 61, 64, 66, 67, 90, 96, 99, 100, 102, 104, 105, 165, 187 accessibility, 51, 56, 58 accommodation, 70, 76, 79, 117 acetaminophen, 31 achromatopsia, ix, 69, 82, 84 acid, x, 14, 19, 22, 23, 24, 38, 72, 115, 119, 120, 121, 122, 123, 124, 126, 127, 130, 132, 134, 206, 212 acidic, 120 acquired immunodeficiency syndrome (AIDS), 4, 5, 8, 10, 15, 18, 48, 170 acromegaly, vii, x, 135, 141, 143, 144, 145, 146, 147, 149, 150, 151, 152, 153, 155, 156, 157, 158 ACTH, 143 actinomycosis, 93 action potential, 80 acute myeloid leukemia, 19 adaptation, 52, 60, 70, 161, 163, 175 adaptive immunity, 161, 162 adenine, 19 adenocarcinoma, 206 adenoma, x, 135, 139, 145, 146, 147, 150, 155 adhesion(s), ix, x, 77, 102, 115, 116, 117, 122, 124, 126, 127, 128, 129, 130, 133, 134, 200, 205, 210, 212, 213, 214 adrenal glands, 169 adsorption, 116 adults, vii, 27, 29, 70, 150, 157, 177, 206

advancement, 100, 150, 154, 156, 158, 209 adverse effects, viii, 22, 23, 26, 27, 33, 163 aetiology, 80, 202, 203 Africa, 182, 205, 206, 210 age, viii, x, 22, 27, 32, 76, 78, 82, 135, 136, 137, 138, 139, 140, 141, 150, 151, 206 agencies, 59, 192 agglutination, 167 aggregation, 49, 75 aggregation process, 49 agonist, vii, 21, 24, 34, 35 airways, 154 albinism, 77 albumin, 170 alcohol dependence, 37 alcohol use, 37 alcohol withdrawal, 23, 37 alcoholics, 37 algae, 166, 167 allergens, 179 allergic bronchopulmonary aspergillosis, 171 allergic reaction, 164 ALT, 31 alters, 79, 206, 210 aluminum oxide, 101 alveoli, 172 amalgam, 101, 112, 113 amputation, 92 amylase, 31 anaerobic bacteria, 112 anastomosis, 93, 211, 212, 215 anatomy, xii, 92, 102, 217, 218 anchorage, 129, 134 aneurysm, 81 angiography, 32 angulation, 97 aniridia, ix, 69, 71, 75, 77, 84, 85 annular pancreas, 213


226

Index

anodization, x, 115, 124 ANS, 154 antibody, xi, 159, 162, 163, 166, 167, 169, 170, 173, 176, 220, 221 anticardiolipin, 219, 220, 223 anti-fungal vaccines, xi, 159 antigen, xi, 159, 162, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 176, 177, 178, 179 antigen-presenting cell(s), 162 anti-microbial medications, vii, 1 antispastic medications, vii, 21 antiviral agents, 3 antiviral therapy, 7 anus, 208 anxiety, 137 aortic valve, 11 apex, 92, 97, 98, 100, 103, 105, 110 aphakia, ix, 69, 71, 75, 76, 84 apical abscess, 93 apical microsurgery, vii, ix, 89, 92, 93, 94, 95, 96, 102, 103, 105, 107, 109, 113 apical periodontitis, ix, 89, 95, 107, 109, 110 apical seal, 96, 113 apical surgery, ix, 89, 91, 92, 93, 94, 96, 97, 99, 100, 101, 102, 107, 110, 111, 113 apnea, x, 149, 153, 156, 157 apoptosis, 116 appendectomy, 214 appointments, 56 aqueous humor, 73, 77, 79 arabinoside, 19 Argentina, 169 arrhythmias, 28 artery(s), xii, 75, 82, 143, 156, 217, 218, 220 arteriosclerosis, 220 arthritis, 5, 80 arthrosis, x, 149, 150 Asia, 182, 205 aspergillosis, 5, 7, 12, 14, 17, 19, 171, 179 aspergillus, vii, xi, 1, 2, 3, 5, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 159, 160, 163, 165, 166, 171, 179 aspirate, 5, 31 aspiration, 22, 24, 28, 31, 33, 35, 210 aspiration pneumonia, 22, 28, 31, 33 assessment, vii, viii, 39, 40, 41, 43, 44, 49, 62, 86, 92, 112, 157, 193, 201, 209 asymptomatic, 4, 9, 28, 143, 164 atherosclerosis, xii, 81, 217, 218, 219, 220, 221, 222, 223 atherosclerotic vascular disease, 222 Atropine, viii, 22 auscultation, 202

authentication, 46, 53, 57, 58 authority(s), xi, 48, 56, 58, 181, 184, 188, 190, 191, 192, 195 autoantibodies, 221 autoimmune disease(s), 85, 160, 223 autoimmunity, vii, xii, 217, 218, 220, 221, 223 autologous bone marrow transplant, 19 autonomic nervous system, 76 autopsy, 12 autosomal dominant, 75, 83 autosomal recessive, 75, 77, 82, 83

B back pain, 22 baclofen overdose, viii, 22, 27, 28, 32, 34, 35, 36, 37 baclofen toxicity, vii, 21, 23, 26, 27, 28, 29, 30, 32, 33, 34, 35 bacteremia, 16, 18 bacteria, ix, xii, 2, 9, 72, 74, 80, 89, 92, 93, 101, 112, 126, 127, 128, 134, 200, 217, 219, 220, 221 bacterial fermentation, 201 bacterial infection, 3 bacterial pathogens, 168 bacteriostatic, 101 barbiturates, 23, 24 barium, 202, 207 barium enema, 207 barriers, 166 base, 61, 66, 138, 205, 206, 212 behaviors, 23 benefits, 5, 52, 62, 94, 109, 169 benign, 70, 73, 84, 86, 150 benzodiazepine, 23 bilateral, 20 bile, 206 biocompatibility, 100, 112, 128 biocompatible materials, 92 biological systems, 116 biomarkers, 223 biomechanics, 117 biomedical applications, 132 biopsy, 7, 14, 17 birth weight, 160 bismuth, 101 bladder spasticity, vii, 21 blastomycosis, 171, 178 bleaching, 112 bleeding, 127, 205, 212 blepharitis, ix, 2, 11, 69, 72, 84, 86 blepharospasm, ix, 69, 70, 72, 73, 78, 84, 85, 86 blind spot, 81 blindness, 10, 70, 77, 79


Index blood, 4, 5, 10, 24, 30, 31, 46, 73, 75, 79, 80, 81, 82, 116, 132, 200, 201, 202, 205, 206, 209, 219, 221 blood cultures, 10 blood pressure, 209 blood stream, 80, 221 blood supply, 81, 82, 200, 205 blood vessels, 73, 75, 79, 81 blood-brain barrier, 24 bloodstream, 166, 172 body fluid, 124 bonding, 130 bone(s), vii, ix, x, 1, 2, 5, 8, 9, 10, 14, 16, 18, 19, 20, 96, 99, 101, 102, 104, 105, 111, 113, 115, 116, 117, 118, 122, 124, 125, 126, 127, 128, 130, 131, 132, 133, 134, 149, 150, 151, 152, 154, 171 bone cells, 132 bone form, 128, 152 bone marrow, vii, 1, 2, 5, 8, 9, 10, 14, 16, 18, 19, 20 bone marrow transplant, 9, 10, 14, 16, 18, 19, 20 boosters, 161 bowel, xi, 26, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215 bowel obstruction, 200, 201, 202, 203, 205, 210, 211, 212, 213, 214, 215 bowel sounds, 201, 202 bradycardia, viii, 22, 24, 27, 28 brain, ix, 5, 7, 23, 26, 27, 28, 32, 36, 69, 75, 80 brain abscess, 5 brainstem, 32, 72 branching, 96 Brazil, 89, 115 breathing, 150, 153, 157 Britain, 113 brucellosis, 80 buccal surfaces, x, 149 buphthalmos, ix, 69, 70, 75, 77, 78, 84, 87

C CAD, 220 caecum, 210 calcifications, 91, 95, 96 calcium, x, 24, 38, 100, 101, 106, 111, 115, 124, 134, 165 calcium carbonate, 100 caliber, 94 Cameroon, 199 campaigns, 48 canals, 91, 93, 95, 96, 98, 109, 110, 111 cancer, 23, 48, 160, 161, 210, 223 Candida, vii, xi, 1, 2, 4, 5, 7, 10, 11, 12, 14, 20, 159, 160, 162, 163, 164, 165, 166, 167, 168, 175, 176, 177

227

candida albicans, 20 candidates, 144, 156, 164, 165, 167, 171, 173, 179 candidiasis, 160, 162, 163, 166, 168, 175, 176, 177 cannabinoids, 31 CaP, 123, 124 capillary, 81, 82 capsule, 76, 79, 161, 163, 170 carbon, 100, 161, 165 carbon dioxide, 100 carbon nanotubes, 165 carcinoma, 202, 205, 210, 211 cardiac conduction abnormalities, viii, 22, 27 cardiac enzymes, 28 cardiovascular disease(s), 218, 219, 222, 223 cardiovascular risk, 220, 221 Caribbean, 62, 63, 64, 65, 66 cartilage, 152 cascades, 161 cataract, 70, 76, 77, 80, 83, 84, 85 catatonia, 27 catecholamines, 24 catheter, viii, 22, 26, 29, 30, 32, 34, 38, 209 cavity preparation, ix, 89, 92, 98, 99, 100, 101, 106, 107, 108 CD8+, 169, 172, 179 cell body, 117 cell division, 169 cell surface, 163 cellular immunity, 162 cellulitis, 2, 11 central nervous system, 8, 17, 22, 23, 24 central sleep apnea, 153 ceramic, 130 cerebral palsy, 23 cerebrospinal fluid, 29, 30, 34 cerebrovascular disease, 136, 141 certificate, 57 certification, 184, 185 Chad, 182 challenges, xi, xii, 19, 160, 174, 175, 217, 218 chemical(s), 74, 80, 92, 97, 101, 112, 116, 117, 132, 164, 184 chemical properties, 112, 132 chemotherapy, 3, 160, 161 Chicago, 66, 177 childhood, xii, 75, 77, 172, 218, 221 children, 19, 29, 62, 70, 72, 86, 169, 182, 206, 208 chitin, 161, 169 Chlamydia, 218, 222 cholesterol, 75, 93 chorea, 23 chorioretinitis, 7, 9, 11, 12 choroid, vii, 1, 2, 75, 79


228

Index

chromatography, 30, 31 chromosome, 75, 77, 82 chromosome 10, 82 chronic diseases, 60 chronic rejection, 13 chronic renal failure, 170 cigarette smoking, 218 circadian rhythm, 83 circulation, 182, 219 citizens, 41, 43, 48, 49 classification, 51, 86, 155, 174 clinical application, 47, 164 clinical diagnosis, viii, 3, 22, 35, 48, 83 clinical examination, 4 clinical presentation, 30, 35, 211 clinical symptoms, 3, 33, 34 clinical syndrome, 23, 24, 153 clinical trials, 12, 50, 130, 163, 164 cloning, 169 closure, 46, 70, 72 CNS, viii, 22, 23, 27, 28, 32 CNS depressant, viii, 22 CO2, 31, 120, 161 coatings, 123, 125, 128, 130, 134 cobalt, 137 coccidioidomycosis, 169, 173, 178 cognitive impairment, 202 colectomy, 211 colic, vii, xi, xii, 199, 201, 209, 212 colitis, 12 collaboration, 55, 58 collagen, 73, 102, 152 colleges, 41 coloboma, ix, 69, 71, 75, 79, 84, 86 Colombia, 182 colon, xi, 199, 200, 201, 202, 203, 208, 210, 211, 212, 215 colonization, 90, 97, 116, 126, 127, 132, 133, 162, 220 colonoscopy, 205 color, 76, 79, 80, 82, 83 color blindness, 82 coma, viii, 22, 27, 28, 30, 32, 33 commensalism, xi, 160, 162, 163, 174, 175 commerce, 183, 185, 191 commercial, 182, 183, 187, 188, 192 communication, xi, 53, 54, 62, 65, 101, 181 communication technologies, 65 community(s), 74, 187, 189 comparative analysis, 49 complete blood count, 103 complexity, 61, 174, 176, 192 compliance, 64, 185, 191

complications, viii, xii, 3, 7, 9, 15, 16, 18, 19, 20, 21, 29, 30, 32, 33, 34, 91, 92, 102, 103, 104, 110, 143, 151, 217, 218 composition, 116, 117, 122, 124, 126, 164 compounds, 164, 169 computed tomography, 32, 38, 103 conception, 43, 75 condensation, 105 conduction, viii, 22, 27, 28, 209 confidentiality, 51, 53, 54, 56, 60, 61 configuration, 150 conflict, 190, 191, 195 conjunctiva, 72 conjunctivitis, 2, 11 connective tissue, 75, 93, 95, 102, 111, 152, 220 consciousness, 27, 33 consensus, 58, 145 consent, 104, 193 constipation, 200, 202, 211 constituents, 72 construction, 42, 65 consulting, 94 consumers, 193, 196 consumption, 19 consumption coagulopathy, 19 contaminant, 205 contamination, 97, 128 contradiction, 190 control group, 151 controlled trials, 17 controversial, 58, 163 controversies, 58 cornea, ix, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 81, 84 corneal dystrophy, ix, 69, 75, 84 coronary artery disease, 219, 221 coronary atherothrombosis, vii, 219, 222 coronary heart disease, 222, 223 correlation, 145, 213, 220, 221 corruption, 54 cortex, 71, 105 cortical bone, 105 corticosteroid therapy, 9 corticosteroids, 3, 7, 12, 160 cortisol, 138 cosmetics, 184 cost, x, 23, 47, 48, 93, 96, 135, 144, 169, 174, 185, 187, 189, 203, 212 cough, 172, 201 coughing, 201 counterfeiting, 198 cranial nerve, 143, 146 craving, 37


Index creatine, 30 creatine phosphokinase, 31 creatinine, 24, 30 cross-sectional study, 156 crowns, 152 CRP, 219, 221 cryptococcosis, 15, 163, 166, 176, 178 crystalline, 75, 79, 81 crystallinity, 130 crystals, 75, 93, 100, 124 CSA, 169 CSF, viii, 22, 24, 28, 29, 30, 34 CT scan, 31, 32, 37, 53, 66, 203, 205, 211, 213, 214 cues, 102 culture, 101, 164 culture medium, 101, 164 cure(s), 14, 111, 136, 145, 146 cyanosis, 172 cycles, 12 cyclophosphamide, 13, 167 cyclosporine, 7, 9, 11, 12, 15 cystic fibrosis, 208, 209 cytokines, xii, 162, 167, 214, 217, 218, 220 cytomegalovirus, vii, 1, 2, 3, 4, 12, 15, 16, 17, 18, 19, 20, 222 cytomegalovirus retinitis, 12, 15, 16, 17, 18 cytoreductive therapy, 20 cytoskeleton, 116, 131

D dacryocystitis, 7 daily living, 25, 86 Darfur, 189 data collection, 51, 193 data processing, 54, 193 data set, 56, 57, 58 data structure, 51 database, 43, 55, 57, 58 DDT, 213 deaths, 2, 27, 30, 197, 209, 215 debulking surgery, 155 decentralisation, 190 decontamination, 28, 33 defects, 28, 71, 73, 97, 118, 131, 173, 200, 206 deficiency(s), 17, 143, 162, 205 deficit, xi, 181, 185 degenerate, 79 dehydration, 200, 202 delirium, 33 dendritic cell, xi, 159, 162, 164, 167, 170, 172, 177, 178, 179 denial, 60

229

dental implants, x, 115, 116, 118, 128, 129, 130, 131, 132, 133, 134 dentin, 97, 101, 111 dentist, 93, 125 Department of Health and Human Services, 58 depolarization, 24 deposition, 75, 100, 101, 111, 123, 127, 152, 172 depression, viii, 2, 22, 23, 24, 26, 27, 28, 33, 74, 81 depth, 98, 99, 104 destruction, 2, 172 detachment, 71, 74, 82, 83, 122 detectable, 202, 219 detection, viii, 13, 14, 22, 80, 83, 163 developed nations, 184 developing countries, vii, 182, 188, 198 developmental disorder, 84 deviation, 97, 99 diabetes, 5, 14, 80, 82, 151, 218 diabetic retinopathy, 9, 83 diagnostic criteria, 86 dialysis, 32, 33, 37 diaphragm, 76 diazepam, viii, 22, 32 diet, 205, 211 dietary habits, 205 diffusion, 92, 201 dilation, 26, 86 dimorphism, 161 directives, 58, 184, 185 disaster, 182 discharges, 32 disclosure, 186 discomfort, ix, 69, 70 disease activity, 145, 151, 153 diseases, 5, 48, 80, 82, 128, 160, 161, 171, 174, 175, 176, 218 disinfection, 91, 95, 96, 98 disorder, ix, 16, 37, 69, 79, 82 displacement, 150 distortions, 103 distress, 24, 193 distribution, 27, 33, 172, 182, 184, 187, 188, 189, 190, 191, 192, 193, 202 diuretic, 200 diversity, 48 DNA, 164, 165, 166, 169, 173, 178, 179 doctors, 41, 43, 187, 189, 192, 193 dogs, 111, 131, 171 DOI, 129 dominance, 165 donors, 5, 11 DOP, 184, 185, 186, 189, 197 dopamine, 137, 140, 144, 151


230

Index

dopamine agonist, 140, 144, 151 dopaminergic, 25 dorsal horn, 24 dosage, 186 dosing, viii, 4, 22, 25, 26, 29, 30 drainage, viii, 22, 203, 214 drinking water, 168 drug abuse, 160 drug delivery, 34 drug resistance, 182 drug smuggling, 192 drug toxicity, 24 drug withdrawal, 26 drugs, vii, ix, x, 16, 23, 27, 32, 33, 69, 84, 115, 124, 125, 140, 144, 182, 184, 186, 187, 189, 194, 197, 198 dry eyes, 70, 73 drying, 123 duodenum, 199, 203, 206 DVT, viii, 22, 35 dyspnea, 172 dystonia, 38, 72, 85

E Eastern Europe, 210 echocardiogram, 28 ecology, 172 ectoderm, 75, 76, 77 edema, 4, 105 editors, 62, 63, 64, 65, 66 education, viii, 39, 41, 42, 48, 50 efficient resource allocation, 40 electroencephalogram (EEG), 25, 27, 28, 31, 32, 36 electrolyte, viii, 22, 28, 33, 123, 124, 200, 209, 212 electrolyte imbalance, 200 electron, 131 electroporation, 165 elongation, 150, 152 elucidation, 205 embolism, 81 emergency, 22, 26, 31, 32, 34, 35, 41, 44, 45, 47, 54, 56, 200, 205, 210, 211, 213 emission, 85, 116 employment, 172 encephalopathy, 37 encoding, 169, 179 encryption, 53 endocrine, 136, 144, 147, 153 endocrinology, 140 endoscope, ix, 89, 107 endothelial cells, xii, 217, 218, 219, 220, 221 endotoxins, 101

endotracheal intubation, viii, 22, 28, 33 end-stage renal disease, 30 energy, 80, 116, 126, 167 enforcement, 185, 191, 192 enlargement, x, 78, 149, 150, 154, 155 environment(s), 48, 101, 126, 127, 162, 163, 191 enzyme, 72, 126, 161, 162, 167, 177 epidemic, 160 epidemiologic, 48 epidemiology, xi, 109, 179, 199, 214 epigastrium, 199 epithelial cells, 162, 220 epithelium, 73, 74, 80 epitopes, 167, 176 Epstein-Barr virus, 5, 19 equipment, 34, 43, 44, 46, 47, 54, 61, 100, 106, 122, 186 Estonia, 40, 62 etching, x, 115, 119, 120, 121, 122, 123, 124 ethanol, 23, 31 etiology, 72, 218 eukaryotic, 161 Europe, 167, 205, 206 European Union (EU), ix, 40, 42, 50, 55, 57, 58, 59, 60, 61 evidence, xi, 7, 9, 11, 37, 48, 51, 77, 87, 154, 155, 156, 170, 181, 205, 207, 218, 222 evolution, 42, 49, 92, 99, 223 examinations, vii, 1, 9, 11, 14, 15, 92, 103, 153 excision, 156 excitation, 72 execution, 41, 50, 91 expenditures, 169 exposure, ix, 69, 70, 92, 154, 162, 163, 171, 203, 219, 220, 222 extracellular matrix, 102, 116 extracts, xi, 159, 164, 165, 166 extraocular muscles, 75 extrusion, 93, 95, 96 eye infections, vii eye-related photophobia, vii, 71, 84

F facial nerve, 74 facial pain, 86 fat, 200 FDA, xi, 22, 29, 101, 159, 164 FDA approval, 29 federal government, 41, 58 fever, 4, 168, 172, 209 fibers, 24, 73, 75, 76, 79 fibrillation, 25


231

Index fibrinogen, 116, 218 fibrinolysis, 205, 214 field tests, 50 fillers, 106 filling materials, ix, 89, 100, 107, 111, 112 films, 117, 202 filters, 14, 34 filtration, 24 financial, 40, 44, 49 fingerprints, 82 first generation, 118 first molar, 94 fistulas, 30 fixation, 116 flaws, 58 flexibility, 52 flexor, 25 floaters, 7, 71, 80, 83 flora, 206, 222 fluid, 28, 34, 83, 127, 160, 201, 202, 204, 205, 209, 212 fluid balance, 209, 212 fluorescence, 126 follicles, 72 food, 202 Food and Drug Administration (FDA), 22 foramen, 95, 96, 97, 99 Ford, 101, 108, 110, 112 formation, ix, 75, 89, 95, 101, 105, 106, 111, 124, 126, 128, 130, 131, 132, 143, 161, 166, 170, 205, 208, 212, 214 foundations, 58 fovea, 81 fovea centralis, 81 fractures, 32, 34, 97, 99 fragments, 163 free energy, 126, 132 freezing, 191 functionalization, 132 fungal infection, vii, x, xi, 1, 3, 5, 10, 12, 14, 19, 159, 160, 161, 162, 163, 166, 173, 175, 178 fungal vaccines, vii, 162, 164, 165, 166, 174, 176 fungi, xi, 2, 9, 14, 74, 80, 160, 161, 162, 163, 164, 165, 167, 173, 175 fungus, xi, 5, 159, 160, 161, 162, 163, 164, 166, 169, 170, 171, 172, 174, 175, 176 fungus spores, 160

G GABA, 23, 24, 25, 28, 37 gadolinium, 139

gamma knife radiosurgery, vii, x, 135, 136, 137, 139, 140, 142, 145, 146, 147 ganglion, ix, 27, 69, 71, 73, 76, 83, 84, 85 gastrectomy, 205 gastric lavage, 33 gastroesophageal reflux, vii, 21, 23 gastrointestinal tract, vii, 21, 24, 211 gene expression, 116, 176 genes, 5, 75, 77, 82, 161, 172 genetics, 77, 85 GH-producing adenomas, vii, 136, 137, 140, 141, 142, 144 GH-producing pituitary adenomas, x, 135, 136 gingival, 102, 104, 127 gingivitis, 220 glasses, 84 glaucoma, 76, 77, 78, 79, 85, 87 glucose, x, 31, 103, 135, 136, 138, 139, 140, 141 glutamate, 24 glycoproteins, 116, 172 governance, 57, 198 governments, 55, 182, 184, 191 GPA, 172 gracilis, 126 granulomas, 93 growth, x, 72, 102, 116, 132, 135, 136, 141, 142, 145, 146, 147, 149, 150, 151, 153, 155, 157, 161, 162, 170, 174 growth factor, x, 135, 136, 141, 145, 146, 153 growth hormone, x, 135, 136, 145, 146, 147, 149, 150, 152, 153, 157 guidelines, 30, 35, 58, 64, 134, 157, 183, 184, 198 gutta-percha, 95, 96, 105, 106, 111

H HAART, 4, 8, 10 half-life, 26, 32 hallucinations, 25, 27, 28 hardness, 206 headache, 80, 86 healing, 95, 102, 104, 107, 113, 130, 205, 214 health, viii, ix, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 164, 165, 169, 183, 184, 185, 187, 190, 192, 193, 195, 219, 222, 223 health care, 62, 63, 64, 187, 190, 193 health care professionals, 193 health condition, 185 health information, viii, 39, 42, 50, 51, 57, 59, 60, 61, 62, 63, 66 health problems, 40, 49 health services, 40, 41, 64


232

Index

health status, 41, 43, 45, 165, 219 healthcare information system, viii, ix, 39, 40, 41, 42, 43, 44, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61 healthcare systems, vii heart block, 25 heart disease, 218, 222 heart rate, 26 heart transplantation, 16, 17, 19, 20 heat shock protein, 163, 167, 169, 172, 176, 177, 179 height, 104, 150, 207 Helicobacter pylori, 218, 222 hematomas, 30 hemodialysis, viii, 22, 28, 30, 33, 35, 37 hemorrhage, 32 hepatitis, 4 hernia, 200, 202, 204, 211, 213 herpes, vii, 1, 2, 4, 5, 7, 8, 9, 10, 11, 12, 13, 15, 19 herpes infections, 15 herpes simplex, vii, 1, 2, 5, 8, 9, 12 herpes simplex keratitis, 9 herpes virus, vii, 1, 5, 19 herpes zoster, vii, 1, 2, 5, 8, 9, 10, 11, 13 herpetic keratitis, 7 heterogeneity, 52, 87 HHS, 58 high risk patients, vii, 1 highly active antiretroviral therapy, 18 hippocampus, 23 histoplasmosis, 172, 179 HIV, 8, 16, 18, 160, 172, 174 HLA, 15, 80, 87 HLA-B27, 80, 87 hormone(s), 137, 138, 143, 145, 153, 161, 223 host, xi, xii, 2, 3, 20, 55, 93, 95, 125, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 172, 174, 175, 176, 177, 178, 179, 218, 220, 221, 222 human immunodeficiency virus, 8, 18 human resources, 40, 47, 54 human subjects, 168 humoral immunity, 162, 163 hydrofluoric acid, 120, 124 hydroxide, 100, 101, 106, 111, 164 hydroxyapatite, x, 115, 122, 124, 129, 130, 132, 133, 134 hydroxyl, 101 hygiene, 72, 127 hyoid, 153 hyperactivity, 28, 73 hyperalimentation, 160 hyperemia, 71 hyperlipidemia, 218 hypernatremia, 22

hyperopia, 70, 76 hyperplasia, 158, 206 hypertension, viii, 14, 22, 27, 28, 31, 33, 218 hyperthermia, viii, 22, 29 hypertrophy, 152 hypoglossal nerve, 156 hypogonadism, 143 hyporeflexia, 27, 28, 33 hypotension, viii, 22, 24, 27, 28, 33, 202 hypothermia, 27, 28, 29, 32 hypothyroidism, 143

I iatrogenic, 34, 95, 97, 110 ibuprofen, 38 ideal, 90, 100, 101, 102, 103 identification, viii, 38, 39, 43, 46, 51, 52, 55, 56, 57, 58, 59, 61, 167, 173, 186 idiopathic, 80 IFN, 168, 169 IL-17, 168, 169, 175 ileum, 202, 205, 207, 209, 211 illumination, ix, 89, 107 image(s), 46, 80, 81, 119, 121, 122, 123, 125, 127, 139 imaging modalities, 34 imitation, 124 immersion, 123 immigrants, 169 immobilization, 27, 132 immune activation, xi, 160 immune response, xi, 159, 160, 161, 162, 163, 164, 165, 166, 168, 169, 170, 171, 172, 173, 174, 177, 179 immune system, xii, 2, 8, 74, 161, 162, 170, 174, 217, 218, 219, 220, 221, 222 immunity, 2, 5, 161, 162, 163, 164, 169, 175, 176, 178, 220 immunization, 59, 163, 165, 167 immunocompromised, x, 5, 6, 13, 14, 16, 80, 159, 160, 161, 163, 164, 168, 170, 171, 173, 174, 175, 177 immunodeficiency, 160 immunogen, 163 immunogenicity, 168, 173, 174, 177, 178 immunoglobulin, 162, 171 immunomodulation, vii, 1, 2, 170 immunomodulatory, 162 immunosuppression, vii, xi, 1, 2, 3, 4, 5, 10, 13, 14, 159, 167, 174 immunosuppressive drug(s), x, 2, 3, 159 immunosuppressive therapies, 160


233

Index immunotherapy, 163, 170, 175 impact assessment, 198 impairments, 75, 79 imperforate anus, 207, 215 implant surfaces, vii, ix, x, 115, 117, 124, 126, 127, 129, 130, 131, 132, 133, 134 implantology, 131 implants, x, 115, 116, 118, 120, 122, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134 improvements, 33 impulses, 116 impurities, 118 in vitro, 12, 38, 100, 101, 108, 126, 130, 131, 134, 167, 170, 175 in vivo, 100, 113, 126, 130, 132, 133, 167, 171, 175, 176 incidence, vii, 1, 3, 4, 5, 7, 9, 10, 11, 14, 15, 48, 82, 96, 109, 143, 160, 168, 173, 182, 202 incisor, 94, 95, 151 indium, 32 induction, xi, xii, 3, 4, 9, 13, 159, 167, 217, 218, 221 industry, 41, 182 inefficiency, 51 infancy, 77 infants, 78, 82, 160, 206 infarction, 32, 143, 146, 221, 222 infection, viii, ix, xii, 2, 3, 4, 5, 6, 7, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 28, 34, 72, 74, 80, 89, 92, 96, 97, 99, 102, 110, 128, 129, 161, 162, 163, 167, 168, 169, 170, 171, 172, 174, 177, 205, 217, 218, 220, 221 infectious agents, vii, xii, 217, 218, 221 inflammation, 6, 71, 72, 79, 80, 81, 83, 84, 100, 101, 117, 128, 133, 161, 165, 211, 218, 220, 221, 223 inflammatory mediators, 220 inflammatory responses, 162, 173 influenza, 11, 167, 171 information exchange, viii, 39, 40, 53, 58 information system, vii, viii, 39, 40, 42, 43, 44, 51, 52, 53, 54, 60, 61, 62, 63, 64 information technology, 62, 64 informed consent, 104 infrastructure, ix, 39, 40, 51, 54, 55, 56, 61, 191 ingestion, 5, 24, 26, 27, 28, 30, 32, 33, 35 ingredients, 187 inguinal hernia(s), 205 inheritance, 75, 77, 82, 83 inherited disorder, 77 inhibition, 24, 72, 101, 162, 205 inhibitor, 176 initiation, 5, 34, 162, 175 injections, 12, 187

injury, xii, 22, 23, 31, 32, 33, 74, 77, 80, 83, 143, 205, 217, 218, 221 innate immunity, 162 insertion, 128 inspectors, 193 institutions, 14, 60, 65, 211 insulin, x, 132, 135, 136, 141, 145, 146, 153 integration, 52, 54, 65, 134 integrity, 47, 53, 61 intensive care unit, 23, 26, 27, 31, 34, 35, 160 interface, 117, 133 interference, 13, 77, 84, 102 interferon gamma, 169, 170 International Classification of Diseases, 53 interoperability, 42, 51, 52, 54, 55, 56, 57, 58, 60, 61, 65 intervention, xi, 35, 45, 47, 77, 156, 199, 203, 205, 211, 215 intestinal obstruction, 200, 203, 204, 207, 209, 212, 213, 214 intestine, 202, 203 intoxication, 23, 27, 35 intractable hiccups, vii, 21, 23 intraocular, vii, 1, 3, 14, 18, 78, 79 intraocular pressure, 78 intravenous antibiotics, 34 intravenous fluids, 206 invertebrates, 77 investment, xi, 65, 181 ions, 100, 101 iridocyclitis, 79 iris, 70, 75, 76, 77, 78, 79, 82, 83, 84, 86, 87 iritis, 13, 79 iron, 161, 205 irradiation, 131, 132, 141, 146 ischemia, 27, 214

J Japan, 36, 135, 149 Jordan, 85

K kidney(s), viii, 7, 8, 9, 16, 18, 20, 21, 22, 24, 26, 30, 31, 32, 33 kinks, 30

L laboratory studies, 30 laboratory tests, 14


234

Index

labour market, 189 lactate dehydrogenase, 30 laparoscopy, 214 laparotomy, 200, 203, 205, 207, 208, 211, 214 laser ablation, x, 115, 120 laser radiation, 127 laser surgery, ix, 69 latency, xi, 160, 163, 164, 169 Latin America, 62, 63, 64, 65, 66, 169 LDL, 223 lead, xii, 29, 34, 72, 73, 117, 127, 136, 182, 191, 192, 199, 207 leakage, viii, 22, 91, 101, 108, 112, 191 leaks, 83 learning, 44 legislation, 191, 192 lens, 74, 75, 76, 79, 81, 86 lesions, vii, xii, 3, 13, 21, 90, 92, 93, 97, 98, 102, 103, 107, 109, 113, 137, 141, 202, 210, 212, 217, 218, 220 leukocytosis, 209 leukopenia, 4 liberalisation, xi, 181, 185 life expectancy, 141 lifetime, 76, 83, 144 ligament, 102 ligand, 23 light, ix, 8, 9, 12, 25, 26, 69, 70, 71, 72, 73, 75, 76, 77, 79, 80, 81, 82, 83, 84, 85, 86, 100, 111, 113, 174, 193 light scattering, 71 Lion, 15 lipid metabolism, xii, 217, 218 lipids, 71, 75 liposomes, 165, 166 liquid chromatography, 30 Listeria monocytogenes, 3, 15 liver, 5, 7, 9, 12, 13, 14, 16, 17, 18, 19, 24, 25, 26, 27, 28, 170, 201 liver transplant, 5, 9, 12, 13, 14, 16, 17, 18, 19 liver transplantation, 13, 17, 18, 19 local anesthesia, 137 local authorities, 41 localization, 205 locus, 82, 87 logistics, 40, 43, 47 longevity, 164 longitudinal study, 99, 132 long-term care insurance, 58 low-grade inflammation, 218 lumen, xii, 200, 205, 206, 209, 210, 217, 218 lung transplantation, 11, 12, 16, 20 Luo, 177

lupus, 80 lymph node, 169, 171, 172 lymphadenopathy, 4 lymphocytes, 168, 221 lymphoid, 206 lymphoma, 17, 206 lysozyme, 72

M macroglossia, x, 149, 152, 154, 155, 156, 157, 158 macrophages, 162, 172 macular degeneration, 82 magnesium, 101 magnetic resonance imaging, 214 magnitude, 121, 122, 123, 125, 169 malignancy, 170, 202, 205, 210 malignant hypertension, 81 malignant hyperthermia, 34 malocclusion, x, 149, 152 management, viii, xii, 19, 22, 23, 28, 33, 34, 35, 36, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 51, 52, 53, 54, 56, 59, 60, 61, 62, 63, 64, 65, 85, 91, 109, 110, 155, 157, 158, 160, 167, 174, 199, 203, 209, 211, 212, 213, 214 mandible, 130, 150, 154, 156 manganese, 134 mania, 25, 27 manufacturing, 118, 128, 171, 182, 185, 186 manufacturing companies, 185 mapping, 65, 87 marketing, 183, 184, 185, 187, 190, 191, 192, 193, 194, 195, 196 marketplace, 182 marrow, 14, 17, 18, 19, 20 Mars, 134 masking, 50 mass, x, 30, 31, 135, 136, 201, 202, 203, 205, 206, 211 mass spectrometry, 30, 31 material resources, 43, 44, 47 material surface, 116 materials, ix, 46, 89, 91, 93, 101, 102, 104, 107, 111, 112, 132, 192 matrix, 117 matter, 72, 74, 90 maxilla, 150, 154, 155 maxillary incisors, 152 maxillary sinus, 96, 103 measurement(s), 78, 154 mechanical ventilation, viii, 22, 28, 34, 35 meconium, 207, 208, 209, 215 median, x, 8, 10, 135, 136, 137, 138, 139


235

Index Medicaid, 59 medical, viii, x, 5, 16, 31, 32, 39, 44, 45, 46, 47, 53, 57, 64, 65, 66, 70, 136, 137, 141, 144, 147, 159, 161, 162, 184, 186, 187, 200, 202 medical care, 32 Medicare, 59 medication, x, 8, 34, 51, 59, 90, 95, 105, 106, 135, 138, 139, 140, 144, 192 medicine, vii, 45, 46, 182, 183, 184, 186, 193, 195, 205 melanin, 76, 79, 83, 161 mellitus, 151 membranes, 80, 102 memory, 27, 161, 163, 176 meningitis, ix, 5, 30, 69 mesentery, 205, 211 mesoderm, 75 meta-analysis, 62, 113, 128, 133, 220, 222 Metabolic, 28 metabolic acidosis, 22 metabolic disturbances, 32 metabolism, 33, 76, 161, 164, 167 metabolites, 80 metals, 123 methodology, 124 methylprednisolone, 11 Mexico, 156, 168 MHC, 171 Miami, 18 mice, 77, 163, 166, 167, 168, 170, 171, 172, 176, 177, 178, 179 microbiota, 128, 165, 167 micrometer, 119 microorganism(s), xi, 92, 97, 99, 101, 117, 126, 127, 128, 159, 161, 162, 164, 172, 173, 220 microscope, ix, 89, 92, 99, 107, 110 microscopy, 126 microspheres, 165 microstructure(s), ix, 115, 116, 134 migration, 102, 190, 198, 200 military, 161 mineral trioxide aggregate, ix, 89, 90, 101, 108, 111, 112, 113 mineralization, 100, 111, 112, 116 miosis, 26, 27, 74 mission, 60 misuse, 95 mitochondria, 80 mitosis, 76 MMA, 156, 158 models, 62, 168, 176, 177 modifications, 47, 126, 129, 155, 156 moisture, 101

mold(s), 160, 171, 172 molecular mimicry, xii, 217, 221 molecular weight, 23, 33 molecules, xii, 102, 164, 174, 217, 221 monoclonal antibody, 163 Montenegro, 158 morbidity, xii, 2, 14, 33, 161, 199, 209, 212, 218 morphology, 79, 80, 109, 110, 116, 117, 133, 158 morphometric, 130 mortality, vii, x, xii, 1, 2, 5, 8, 14, 15, 33, 35, 136, 141, 145, 146, 159, 160, 161, 166, 167, 171, 175, 199, 200, 205, 209, 212, 218 mortality rate, 5, 8, 160 motor neurons, 25 Mozambique, 62 MRI, 138, 139, 203 MTA, ix, 89, 100, 101, 106, 107, 108, 111, 112, 113 mucosa, 104, 162, 169, 201 mucous membrane(s), 172, 201 mucus, 201, 206 multiple sclerosis, vii, 21, 80 multiples, 137 mutant, 171, 174 mutation(s), 5, 75, 77, 82, 85, 87 mycobacteria, 14 mycology, 18 myocardial infarction, xii, 200, 217, 218, 219, 220, 221, 222, 223 myopia, 83

N NaCl, 120 nanostructures, 116 narcotic, 205 National Health Service (NHS), 56, 63, 66 national product, 185 National Strategy, 63 Nd, 120, 132 necrosis, 7, 8, 9, 12, 13, 90, 100, 143, 210 negative consequences, 57 negative effects, 163 negative outcomes, 136 negotiating, 95 neonates, 207, 209 neoplasm, 201, 202 nerve, 26, 71, 74, 80, 152, 156, 199 neurologic disorders, vii, 21 neuronal calcium channels, 28 neurons, 24, 25 neuropathy, 73, 143, 146 neurotoxicity, 30, 33 neurotransmitters, 22, 23, 24


236

Index

neutrophils, 162, 172 New England, 198 NGOs, 187, 189, 191, 192, 193, 197 Nigeria, 182, 197, 198 night driving, 84 nigrostriatal, 25 Nile, 189 nitrogen, 30, 172, 201 norepinephrine, 28 Norway, 198 novel materials, 90 nuclei, 83 nurses, 41 nursing care, 35, 56 nutrients, 80 nystagmus, 25, 70, 77, 79, 82

O Obama Administration, 58, 66 obesity, 218 obstacles, 173 obstruction, xi, 96, 199, 200, 201, 202, 203, 204, 205, 207, 208, 209, 210, 211, 213, 214, 215 obstructive sleep apnea, x, 149, 153, 158 occlusal disturbance, x, 149, 150, 156 occlusion, viii, x, 22, 30, 143, 146, 149, 151, 154, 155 occupational health, 48 ocular adnexia, ix, 69, 71, 72, 84 oculomotor, 76, 79 oculomotor nerve, 76, 79 oedema, 211 oil, 83, 85, 164 Oklahoma, 101 opacification, 77 opacity, 76, 78 operations, 146, 193, 205 ophthalmic infections, vii, 1, 3 ophthalmologist, 2 ophthalmoscopy, 4 opiates, 209 opioids, 140 optic nerve, 71, 77, 78, 83 oral cavity, 96, 107, 220 oral health, 128, 219 oral lesion, 221 organ(s), vii, 1, 2, 4, 7, 8, 9, 10, 12, 14, 15, 16, 17, 18, 19, 20, 150, 160, 161, 167, 169, 170, 172 organism, 168, 220 osseointegration, ix, x, 115, 116, 117, 118, 120, 124, 126, 128, 129, 130, 132, 133 osteomyelitis, 5

osteotomy, 154, 155, 156, 157 outpatient(s), 42, 44, 45, 47, 54, 56 oxidation, 124, 134 oxygen, 26

P Pacific, 179 pain, 11, 24, 70, 71, 73, 80, 84, 168, 199, 200, 201, 202, 205, 206, 213 palate, 152, 154, 156 palliative, 212 pallor, 79, 206 palpation, 105 pancreas, 9 pancreatitis, 4 paracoccidioidomycosis, 170, 173, 178 parallel, 47, 78, 99 paralysis, 31, 74 paralytic ileus, 210 parasite, 174 participants, xi, 126, 181, 188, 190, 193 paternalism, 60 pathogenesis, xi, xii, 127, 160, 172, 175, 217, 218, 220, 223 pathogens, xii, 2, 3, 72, 128, 160, 161, 162, 163, 165, 174, 175, 176, 177, 218, 219, 221, 222 pathology, x, 44, 45, 70, 87, 93, 97, 149, 150, 212, 222 pathophysiology, 5 pathways, 23, 24, 82, 85, 97, 138, 143, 146, 175 patient care, 64 PCP, 172 PCR, 4 pellicle, 126 peptide(s), 133, 162, 167, 170, 178 perforation, xii, 74, 90, 91, 95, 101, 110, 199, 200, 207, 210, 211, 212, 214 periapical lesion, ix, 89, 90, 93, 97, 98, 103, 105, 109 periodontal, 102, 105, 126, 128, 134, 151, 152, 219, 220, 222 periodontal disease, 126, 128, 151, 219, 220, 222 periodontitis, ix, 89, 95, 107, 109, 110, 128, 131, 132, 151, 158, 218 periosteum, 104 peripheral blood, 15 peripheral vascular disease, 221 peristalsis, 199, 202 peritoneal cavity, 205 peritoneum, 201 peritonitis, 199, 203, 205, 207, 211 permeability, 165 pH, 31, 101, 124, 161


237

Index phagocyte, 171, 178 phagocytic cells, xi, 160, 162, 172 phagocytosis, 170, 172 pharmaceutical(s), xi, 50, 181, 182, 183, 184, 185, 186, 187, 189, 190, 191, 194, 196, 197 pharmacokinetics, 24 pharmacotherapy, 144 phenotype(s), 116, 117 phenytoin, viii, 22, 28 Philadelphia, 18, 28, 35 phosphate(s), x, 115, 124, 134, 164 phospholipids, 221 photophobia, vii, ix, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 82, 83, 84, 85, 86, 87 physical activity, 73 physicians, 4, 56, 67, 136, 161 physicochemical properties, 116 pigmentation, 77, 79 pilot study, 187 pituitary adenomas, x, 135, 143, 146, 147 pituitary functions, x, 135, 136, 137 pituitary tumors, 145 placebo, 20 plants, 160, 185 plaque, 109, 126, 127, 128, 132, 133, 220 plasma cells, xii, 217, 221 plasma levels, 24, 26, 35 plasmid, 169, 173 plasminogen, 214 plastic deformation, 118 plasticity, 171 platelet aggregation, xii, 217, 218 platelets, 221, 222 pneumococcus, 14 pneumocystis pneumonia, 3 pneumonia, 18, 30, 31, 171, 179, 218 pneumonitis, 4, 10 police, 192, 193 policy, xi, 57, 181, 185, 189, 190, 193, 198 polymer, 166 polymerase, 3 polyp, 206 polysaccharide(s), 166, 167, 169, 170, 178 population, ix, 7, 8, 40, 41, 43, 46, 48, 49, 52, 57, 59, 60, 69, 82, 84, 136, 161, 162, 190, 221 population group, 59 portfolio, 44, 46 positive relationship, 126 positron, 85 post-transplant, vii, 1, 2, 3, 5, 7 potassium, 101, 200, 209 precursor cells, 116 prednisone, 3, 7, 9, 11, 13, 20

prematurity, 206 preparation, 22, 47, 90, 95, 96, 98, 99, 100, 111, 168, 172, 182 presbyopia, 76 presidency, 58 prevention, vii, 1, 2, 3, 19, 48, 125, 176, 214 prevention of infection, 125 primary function, 40, 60, 61 priming, 34 principles, 92, 94, 113 private ownership, 40 private sector, 182, 184, 190 pro-atherogenic, 219 probability, 205 probe, 105, 208 professionals, viii, 39, 40, 41, 43, 46, 47, 48, 49, 50, 52, 56, 57, 60, 61, 90 profit, 57, 187, 191, 192 profit margin, 187 progenitor cells, 102 prognosis, ix, 27, 89, 91, 107, 108, 113 pro-inflammatory, 167 project, 39, 42, 55, 56, 57, 60, 66, 83 proliferation, 92, 102, 116, 129, 131, 173 proline, 169 promoter, 168 prophylactic, xi, 2, 5, 13, 15, 159, 166, 170, 176 prophylaxis, vii, 1, 3, 5, 12, 14, 15, 18, 19, 129, 161 prostheses, 96, 104, 129 prosthesis, 91, 94, 95, 96 protection, 33, 50, 55, 56, 57, 59, 161, 163, 164, 165, 166, 167, 168, 169, 170, 171, 173, 174, 177, 193, 195, 220 protective role, 162, 167 proteinase, 166 proteins, xii, 24, 102, 116, 123, 126, 161, 169, 170, 171, 172, 176, 179, 218, 221, 222 psychosis, 25 public health, 41, 42, 48, 49, 59, 60, 175, 182, 183, 184, 190, 195 public sector, 189, 190, 192, 198 pulmonary embolism, 200 pulp, 112, 152 pumps, 30, 34, 35 pus, 80 pyloroplasty, 205

Q quality assurance, 184, 190, 195 quality control, 48, 182, 186, 190, 195, 198 quality improvement, 59, 64 quality of life, 70, 77


238

Index

R radiation, x, 135, 136, 137, 138, 141, 143, 146, 147, 203, 206 radiation therapy, 136, 137, 141, 143, 147 radio, 144, 202 radiography, 203, 213 radiopaque, 101 radiotherapy, 136, 145, 146, 147 radius, 73, 210 raw materials, 184 reactions, 30, 219, 221, 223 reactivity, xi, 159, 166, 222 reading, 73, 76 rebound tenderness, 201 receptors, 23, 24, 25, 28, 33, 36, 38, 76, 80, 161, 172, 179, 201 recession, 154 recognition, 77, 161, 172, 190, 213 recombinant proteins, xi, 159, 164, 169, 174 recovery, 7, 8, 18, 26, 33, 41, 55, 187 recreational, 35 rectum, 201, 202, 203, 215 recurrence, 93, 138, 155, 211 redundancy, 55 reflexes, vii, 21, 25, 26 reform, 58, 66 regeneration, ix, 89, 102, 113, 131 regression, 107 regrowth, 138, 141 regulations, xi, 181, 182, 183, 184, 187, 188, 190, 191, 192 regulatory framework, 188 regulatory requirements, 184 rehabilitation, 116, 217 reintroduction, 29 rejection, vii, 1, 2, 7, 9, 11, 12, 13, 160 relaxation, 23, 79 relevance, 157 reliability, 194 remission, x, 135, 136, 138, 139, 140, 141, 143, 144, 147 renal failure, 33 renal impairment, viii, 22, 28 renal insufficiency, viii, 22, 27, 30, 35 repair, 90, 91, 93, 95, 100, 101, 102, 110, 112, 126, 214 replication, 161 requirements, viii, ix, 39, 40, 42, 50, 51, 54, 55, 56, 60, 61, 66, 94, 161, 177, 182, 190, 196, 209 researchers, 49, 183 resection, xii, 96, 97, 98, 99, 110, 136, 139, 155, 199, 208, 212

resilience, 160 resistance, x, 5, 159, 160, 162, 163, 178, 205 resolution, 31, 81, 163, 203, 205 resource allocation, 43 resource management, 43, 60 resources, viii, 14, 39, 40, 41, 43, 44, 47, 48, 49, 52, 61, 185, 193 respiration, 153 respiratory acidosis, 22, 31 respiratory depression, viii, 22, 26, 27 respiratory failure, 22 respiratory rate, 26 response, xii, 26, 47, 71, 76, 93, 111, 113, 116, 117, 124, 130, 134, 144, 145, 146, 161, 162, 163, 164, 167, 170, 171, 172, 173, 176, 177, 179, 217, 219, 220, 221 response time, 47 responsiveness, 173 restoration, 34, 96, 97, 98, 102 restorative material(s), 97, 101, 111 restrictions, 57 retail, 104, 184, 185, 186, 190, 191, 193 retina, vii, ix, 1, 2, 7, 13, 23, 69, 70, 71, 73, 75, 76, 79, 80, 81, 82, 83, 84, 87 retinal detachment, ix, 7, 8, 11, 69, 70, 76, 82, 83, 84, 85, 86 retinal disease, 70 retinal dystrophy, ix, 69, 83, 84 retinitis, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 83 retinitis pigmentosa, 83 retinopathy, 7, 9 RH, 16, 18, 19, 37, 65 rhabdomyolysis, viii, 22, 27, 31, 33 rhodopsin, 80, 83 rhythm, 26 ribosome, 179 rights, 50, 66 risk(s), vii, x, xii, 1, 2, 3, 4, 5, 14, 15, 16, 17, 34, 48, 50, 53, 66, 77, 83, 93, 94, 96, 99, 107, 128, 141, 151, 155, 159, 160, 161, 163, 164, 182, 184, 199, 200, 201, 203, 211, 218, 220, 221, 222, 223 risk factors, x, 17, 151, 159, 160, 161, 218, 220, 223 RNA, 162, 171 rodents, 176 rods, 80, 81, 83, 126 root(s), ix, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 103, 105, 106, 107, 108, 109, 110, 111, 112, 113, 152, 211 root canal system, ix, 89, 90, 92, 93, 97 root canal treatment, ix, 89, 92, 93, 96, 109 root-end filling produces, ix, 89 root-end surgery, ix, 89, 113


Index roughness, 116, 118, 120, 121, 122, 123, 124, 126, 127, 132, 133, 134 rules, xi, 181, 185, 191

S safety, 48, 52, 58, 156, 164, 168, 174, 177, 182, 183, 184, 192 salts, 111, 123, 165 sarcoidosis, 80 SAS, 153 saturation, 26 savings, 169 scanning electron microscopy (SEM), 118 scatter, 70 scattering, 75 scedosporium, vii, 1, 8, 11 science, 90, 215 sclera, 74, 75, 78, 79 sclerosis, 23 scotoma, 79 second generation, 12 secretion, x, 116, 135, 136, 141, 149, 153 security, viii, 39, 42, 51, 53, 54, 55, 56, 59, 61, 62, 65, 164 sedative, 23 seizure(s), viii, 22, 25, 26, 27, 28, 32, 33 sellers, 184, 187, 190 sensation, 70, 71, 72, 73, 83, 156 sensitivity, 70, 72, 73, 76, 84, 203, 213 sensitization, 85 sensors, 83 sepsis, 30, 200, 215 septic shock, 215 Serbia, 217 serology, 3, 7 serum, vii, x, 21, 24, 26, 30, 103, 132, 135, 136, 145, 146, 170, 171, 219 serum albumin, 132, 170, 171 services, 40, 41, 43, 45, 46, 51, 56, 57, 185 sex, x, 83, 135, 136, 137, 138, 139, 140, 141, 151 shape, 116, 117, 118, 150, 154 shareholders, xi, 181, 183, 188 side effects, vii, 16, 21, 23, 30, 140, 168, 184 sigmoid colon, 210, 211 signs, 32, 33, 35, 75, 81, 116, 201, 202, 213 silicon, 101 sinusitis, 5 skeleton, x, 149, 150, 155 skin, 30, 70, 72, 75, 152, 162, 168, 169, 171, 201 SLA, 121, 130 sleep apnea, x, 149, 152, 153, 156, 158 small intestine, 215

239

smoking, 5, 14, 84, 220 smooth muscle, 75 smoothing, 103, 105 SMS, 146 snoring, 156 social benefits, 58 social impairment, 153 sodium, 84, 101 sol-gel, x, 115 solution, 34, 84, 120, 123, 124, 155 somnolence, 26 South America, 168, 182 Spain, ix, 39, 40, 42, 56, 59, 60, 61, 62, 63, 64, 65, 66 spasticity, vii, 21, 22, 24, 29, 37, 38 specialists, x, 159 species, 2, 3, 12, 160, 163, 166 specifications, 184, 192 sphincter, 27 spinal cord, vii, 21, 24, 32, 37, 38, 199 spinal cord lesions, vii, 21 spine, 31 spleen, 7, 169, 170 stability, 185 stabilization, 11, 28, 205 stakeholders, 192, 193 standardization, 52, 55, 56, 164 state(s), 5, 59, 61, 70, 100, 107, 125, 151, 155, 162, 163, 183, 185, 186, 187, 189, 190, 191, 192, 193, 195, 202, 214 status epilepticus, viii, 22, 25, 28 steel, 99 stem cells, 102 stenosis, 143, 206, 209 stent, 212 stereotactic radiosurgery, x, 135, 146, 147 stimulation, ix, 69, 76, 83, 84, 90, 138, 201 stimulus, 162 stoma, 208 stomach, 207 storage, 44, 184 strangulated hernia, 205 strategic management, 43, 48 strategic planning, viii, 39, 41, 42, 43 stretching, 210 strictures, 205, 211 stroke, xii, 23, 217, 220, 221, 222, 223 stroma, 74 structural changes, 81 structural protein, 164 structure, viii, xii, 39, 51, 54, 61, 73, 75, 76, 79, 82, 100, 117, 131, 158, 217, 221, 223 structuring, 127


240

Index

subcutaneous tissue, 29 substance use, 36 substrate(s), 117, 123, 124, 129, 134, 218 subtraction, 119 success rate, ix, 89, 90, 94, 99, 100, 102, 107 Sudan, xi, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 194, 196, 197, 198 suicide, 22, 30, 35 sulfate, 101, 164 sulfuric acid, 120 Sun, 122, 134 supervision, 186 suppliers, 188, 192 supply chain, 182 suppression, 5, 31, 32, 147 supraorbital ridges, x, 149, 150, 154 suprapubic, 200 surface area, 127 surface chemistry, 134 surface energy, 116, 134 surface layer, 73, 124 surface modification, 118, 131 surface properties, 116 surface treatment, x, 115, 117, 118, 120, 122, 130, 131, 132 surgical debridement, 14 surgical intervention, 47, 95, 205 surgical removal, 76, 95, 145 surgical resection, 136 surgical technique, ix, 2, 89, 92, 99, 102, 105, 107, 125 surveillance, 2, 44, 48, 59, 162, 184, 187, 190, 193 survival, 2, 136, 161, 167, 169, 177 survival rate, 2 survivors, 5 susceptibility, 2, 85, 160, 162, 210 suspensions, 173 sustainability, 40, 57 suture, 104 sweat, 208 sweat test, 208 Sweden, 15, 136 swelling, 73, 78 Switzerland, 176, 198 sympathetic nervous system, 73 symptoms, 4, 9, 12, 15, 24, 26, 27, 29, 32, 38, 72, 73, 75, 78, 82, 97, 105, 153, 155, 156, 202, 211 syndrome, 17, 23, 36, 37, 70, 80, 85, 153, 157, 158, 206, 214, 215 synthesis, 84, 116, 152, 161 syphilis, 80

T T cell(s), 162, 163, 164, 169, 170, 172, 179 tachycardia, 24, 25, 26, 27, 28, 31, 202 tachypnea, 25, 172 Taiwan, 17 target, xii, 137, 166, 167, 171, 173, 177, 217, 221 target population(s), 173 team members, 190 techniques, ix, 3, 14, 41, 49, 79, 89, 92, 93, 98, 99, 100, 111, 117, 118, 125, 126, 136, 146, 155 technology(s), 40, 41, 90, 91, 123, 174 teeth, ix, x, 89, 93, 94, 96, 99, 104, 108, 109, 110, 128, 133, 149, 152, 219, 220 temperature, 25, 120, 122, 124, 161 temporal lobe, 143 tendon, 26 tension(s), 76, 78, 161, 210 testing, 3, 141, 182 tetanus, 166, 167, 170, 177, 178 Th cells, 162 thalamus, 73 therapeutic agents, 160 therapeutic goal, x, 135, 136 therapeutic use, 33 therapy, x, 2, 3, 4, 5, 8, 9, 10, 11, 12, 14, 16, 17, 28, 29, 34, 77, 93, 97, 98, 99, 108, 110, 112, 136, 137, 140, 141, 143, 144, 145, 146, 147, 156, 159, 161, 210, 215, 223 thermal oxidation, 127 thermoregulation, viii, 22, 35 threats, 160, 162 thrombocytopenia, 4, 20 thrombosis, viii, 22, 221 thyroid, 5, 7, 137 tissue, x, xii, 2, 26, 46, 79, 93, 97, 100, 101, 102, 111, 112, 113, 117, 125, 149, 152, 154, 156, 159, 168, 169, 176, 214, 217, 221 titania, 118, 132 titanium, x, 115, 116, 117, 120, 122, 124, 126, 127, 129, 130, 131, 132, 133, 134 TLR2, 161 TLR4, 161 TNF, 171, 173, 178 tobacco, 151 tonic, 27, 28 tonic-clonic seizures, 27, 28 tooth, 92, 95, 96, 99, 100, 101, 103, 104, 105, 107, 109, 128, 151, 152 torticollis, 23 toxic effect, 23, 29, 32 toxic megacolon, 203


241

Index toxicity, vii, x, xi, 12, 21, 23, 24, 26, 27, 28, 29, 30, 32, 33, 34, 35, 36, 37, 38, 111, 159, 164, 200 toxoplasma, vii, 1, 2, 9, 10, 11, 12, 14, 19 toxoplasmosis, 4, 9, 15, 17, 80 tracheostomy, 154, 157 transduction, 82, 84 transforming growth factor, 75 translocation, 200, 213 transmission, 38, 57, 128, 132, 160 transplant, vii, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 41, 160, 161 transplant recipients, 2, 5, 15, 16, 17, 19, 20 transplantation, 2, 3, 4, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, 160, 162, 170, 179 transverse colon, 200, 211 trauma, 5, 32, 69, 73, 74, 82, 84, 102 tremor, 27, 28 trial, 19, 31, 85, 129, 130, 167, 168, 212, 213 trigeminal nerve, ix, 69, 75, 84 trigeminal neuralgia, vii, 21 trypsin, 208 TSH, 143 tuberculosis, 9, 13, 80 tumor(s), x, 135, 136, 138, 139, 141, 143, 145, 150 tumor growth, 136, 138, 141 tumours, 147 turgor, 201

U ulcer, 71, 73, 74, 76, 84 ulcerative keratitis, ix, 69, 73, 84 ultrasonography, 203 ultrasound, 98, 100, 106, 107, 110, 165, 203, 207, 208, 215 umbilical hernia, 204 undifferentiated mesenchymal cells, 102 unions, 193 United Kingdom (UK), 62, 63, 64, 69, 182, 197, 198, 215 United States (USA), ix, 40, 42, 55, 58, 59, 60, 61, 101, 168, 175, 182, 197, 200, 213 unstable patients, 203 upper airways, 153 upper respiratory tract, 154 urea, 30, 103 uric acid, 103 urinary retention, 28 urine, 30, 31, 210 UV, 76, 81, 165 UV light, 76, 81, 165 uveitis, ix, 7, 8, 10, 16, 18, 69, 71, 74, 79, 80, 81, 84, 86, 87

V vaccine, xi, 159, 160, 161, 163, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179 vaccine design, 176 vagina, 166 vaginitis, 167, 177 validation, 215 valve, 202, 203, 210, 211 vapor, 127 variations, 81 vascular occlusion, 4 vasculature, 104, 156 vasculitis, 221 vasodilation, 23 vasodilators, viii, 22 vein, viii, 4, 22 ventilation, 34, 154 vertigo, 26 vesicle, 75 vessels, 75, 82 viral infection, 12, 14 viruses, 2, 3, 74, 80 vision, vii, viii, 1, 2, 7, 8, 9, 10, 11, 12, 13, 15, 17, 25, 39, 70, 71, 72, 73, 74, 75, 79, 80, 82, 83 visual acuity, 7, 8, 12, 19, 77 visual field, 7, 83 visual system, 71 visualization, 102, 104 vitamin E, 165 volvulus, 201, 202, 205, 207, 209, 210, 211, 214, 215 vomiting, 200, 201, 206, 207

W Washington, 37, 63, 177 waste, 80 water, 164, 169, 203, 208, 211, 214 wavelengths, 73 weakness, 26, 28 wear, 70, 74, 84, 99, 100 weight loss, 200 weight reduction, 156 welfare, 185 West Africa, 198 wettability, 116 white blood cell count, 31 withdrawal, vii, 21, 23, 25, 28, 29, 30, 31, 32, 34, 35, 36, 37 withdrawal symptoms, viii, 22, 23, 31, 34, 37


242

Index

workflow, 47 workload, 213 World Health Organization (WHO), 40, 62, 182, 183, 185, 192, 197, 198 wound healing, 102, 110 wound infection, 30

Z zinc, 111 zinc oxide, 111 zirconium, 127, 133

Y yeast, 160, 164, 166, 168, 169, 170, 171, 172, 174, 175, 177, 178, 179
