bluuebunny/crossref_metadata_2025 huggingface dataset:
Headaches and Chronic Pain
Authors: Clark Michael R.
Published: November 2020

Pain has been defined as ‘‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’’ (Lindblom et al., 1986). Table 5–1 contains definitions of terms commonly used to describe pain sensations (Merskey et al., 1986). Pain is the most common reason a patient presents to a physician for evaluation. The U.S. Center for Health Statistics found that 32.8% of the general population suffers from chronic pain symptoms (Magni et al., 1993). Many factors can influence patients’ reports of pain, including medical and psychiatric disorders, social circumstances, disease states, personality traits, memory of past pain experiences, and personal interpretations of the meaning of pain (Clark and Treisman, 2004). There is no simple algorithm for determining whether the cause of pain is psychologic or neurologic (Clark and Chodynicki, 2005). The clinical evaluation of patients complaining of pain should be comprehensive and incorporate the patient’s descriptions of pain (ie, location, intensity, duration, precipitants, ameliorators); observations of pain-related behaviors (eg, limping, guarding, moaning); descriptions of problems performing activities; and neurologic and psychiatric examinations (Clark and Cox, 2002). Post-herpetic neuralgia (PHN) is defined as pain persisting or recurring at the site of shingles at least 3 months after the onset of the acute varicella zoster viral rash. PHN occurs in about 10% of patients with acute herpes zoster. More than 50% of patients older than 65 years of age with shingles develop PHN, and it is more likely to occur in patients with cancer, diabetes mellitus, and immunosuppression. During the acute episode of shingles, characteristics such as more severe pain and rash, presence of sensory impairment, and higher levels of emotional distress are associated with developing PHN (Schmader, 2002). Most cases gradually improve, with only about 25% of patients with PHN experiencing pain 1 year after diagnosis. Approximately 15% of patients referred to pain clinics suffer from PHN. Early treatment of varicella zoster with low-dose amitriptyline (25–100mg QD) can reduce the prevalence of pain at 6 months by 50% (Bowsher, 1997).
Stimulants and Dopamine Augmenters
Authors: Onyike Chiadi U.
Published: November 2020

Stimulants are typically prescribed for their positive effects on mood, motivation, alertness, arousal, and energy. They are believed to exert their pharmacologic effects by increasing synaptic release of endogenous catecholamines (norepinephrine and dopamine) while simultaneously blocking catecholamine reuptake at the nerve terminals. Themost commonly used ‘‘traditional’’ agents are methylphenidate and dextroamphetamine. Methylphenidate reaches peak blood levels in 1 to 3 hours and has an elimination half-life of 2 to 3 hours. Dextroamphetamine reaches peak levels in 2 to 4 hours and has an elimination half-life of 3 to 6 hours. Controlled-release formulations are available, allowing for dosing once daily. Dextroamphetamine is excreted primarily in the urine in unchanged form, whereas methylphenidate is excreted mainly as ritalinic acid. The newer generation stimulant modafinil has been marketed in the United States since 1998. Initially used in the treatment of narcolepsy, it is now prescribed for a wider range of conditions because of its positive effects on wakefulness, vigilance, cognitive performance, and mood. Its pharmacologic effects are thought to result primarily from the stimulation of wakefulness-promoting orexinergic neurons in the anterior hypothalamus. Inhibition of norepinephrine reuptake in the ventrolateral preoptic nucleus and of dopamine reuptake (by binding to the transporter) may contribute to its action. Modafinil is administered orally, achieves peak plasma concentrations in 2 to 4 hours, and has an elimination half-life of 12 to 15 hours. It is 90% metabolized in the liver, and its metabolites are excreted in the urine. The ergot alkaloids bromocriptine and pergolide are familiar to most neurologists in their use in the treatment of Parkinson’s disease (PD) and migraine headache. These dopamine receptor agonists are also used in neuropsychiatry in the treatment of apathetic states in patients recovering from brain trauma, cerebral anoxia, and strokes. Amantadine is another familiar agent used in the treatment of PD and drug-induced parkinsonism. In addition to other effects in the central nervous system (CNS), amantadine facilitates dopamine release and inhibits its reuptake. It thus has modest ‘‘stimulant-like’’ effects useful in the treatment of executive dysfunction syndromes, particularly in patients with dementia. Bupropion is a dopamine and norepinephrine reuptake inhibitor. It usually is prescribed as a ‘‘nonsedating’’ antidepressant, but its potentiation of catecholamine neurotransmission results in modest stimulant-like clinical effects.
Psychotherapy
Authors: Lehmann Susan W.
Published: November 2020

To nonpsychiatric physicians the term psychotherapy often sounds vague and mysterious. Yet, the art of providing healing through the clinician–patient relationship is as old as medicine itself. Psychotherapy is a form of treatment that uses psychologic techniques within the context of this confiding clinician–patient relationship to treat mental symptoms and relieve emotional distress. Psychotherapy may be the main approach to treatment of identified symptoms, or it may be used as an adjunct to pharmacotherapy. The clinician–patient relationship at the core of psychotherapy can be distinguished from other confiding relationships a person may have with family members, friends, mentors, and advisors. In psychotherapy, there is a clearly identified provider of care and a recipient of that care. The provider is specially trained to deliver the care in a professional and coherent way, using specific psychologic techniques. Both the provider and the patient focus their attention on the patient’s specific problems and work together in partnership to address the elements of psychologic distress and improve the patient’s symptoms. The goal of psychotherapy may differ depending on the patient and his or her situation. Sometimes, the goal of psychotherapy is symptom reduction (eg, to decrease anxiety, improve mood, or reduce friction in an interpersonal relationship). It may be used to help an individual replace unhealthy, counterproductive ways of thinking or reacting with more adaptive ones. In other instances, the goal of psychotherapy may be educational or instructive and involve teaching techniques to expand an individual’s coping abilities or communication skills. All forms of psychotherapy develop an individual’s self-awareness and help bolster appropriate self-esteem. The therapeutic setting between patient and clinician establishes validation that the patient’s concerns are worth addressing and provides a sense of hopefulness that things can improve. As new options are explored and new techniques for dealing with distressing situations are discussed, patients develop an increased sense of mastery and feel less overwhelmed by life circumstances. Psychotherapy may take three main forms of: (1) individual, (2) couples or family, or (3) group. In individual psychotherapy, a single patient and therapist work together, focusing on the patient’s unique attitudes, perceived experiences, and behaviors that are associated with his or her current distress.
The Legacy of European Colonialism
Authors: Knapp Gregory
Published: November 2020

South America was first “encountered” by Europeans during Columbus’ third voyage in 1498. This marked the end of the pre-Columbian period of the continent, and the beginning of the colonial period that lasted until the end of the wars of independence in the early nineteenth century. Total liberation of the continent from Spain was finally achieved at the Battle of Ayacucho in 1824. Brazilian independence from Portugal was achieved more peacefully in 1822, when Dom Pedro became constitutional emperor. The Guianas remained colonies far longer; indeed Guyane (French Guiana) is still an overseas department of France, while Suriname (Dutch Guiana) became independent in 1975, and Guyana (originally a Dutch colony, later British) became independent in 1966. It could be suggested that dependency remained after the end of formal colonial rule, owing to the continued influence of global economic powers on the continent. However, for the purposes of this chapter, the colonial period can be considered as lasting for 326 years from 1498 to 1824. If recent research has tended to enhance our appreciation of the impact of pre-Columbian peoples on the South American environment, it has also corrected some stereotypes concerning European colonial impacts. Europeans were not the first to substantially impact the South American environment. The colonial period was generally marked by depopulation and agricultural disintensification, with the result that many environments were more “pristine” at the end of the eighteenth century than at the end of the fifteenth century. Migrations, cultural hybridities, and new local, regional, and global economic linkages led to changes in demands on agriculture and resource extraction. New technologies, crops, and social structures also had an impact. These impacts were not always as negative as sometimes portrayed, and local populations often had a substantial say in the outcome. Many of the most noticeable impacts resulting from the encounter with Europeans did not become widespread until after independence (McAlister, 1984; Bethell, 1987; Hoberman, 1996; Hoberman et al., 1996; Mörner, 1985; Newson, 1995; Robinson, 1990; Butzer and Butzer, 1995).
The Heirs of Odysseus, 800 BC–550 BC
Authors: Abulafia David
Published: November 2020

Whether the early Greeks possessed as powerful a sense of identity as the Phoenicians is far from clear. Only when a massive Persian threat appeared to loom from the east, in the sixth century, did the diverse Greek-speakers of the Peloponnese, Attika and the Aegean begin to lay a heavy emphasis on what they had in common; the sense of a Hellenic identity was further strengthened by bitter conflicts with Etruscan and Carthaginian navies in the west. They knew themselves as distinct groups of Ionians, Dorians, Aeolians and Arcadians, rather than as Hellenes. There were the Spartans, proud inheritors of the Dorian name, who saw themselves as recent immigrants from the north. There were the Athenians, who insisted they were the unconquered descendants of more ancient Greeks. There were the Ionians, thriving in the new settlements across the Aegean, in Chios, Lesbos and on the Asian coast. The ‘Greeks’ cannot be identified simply as those who took delight in tales of the Greek gods and heroes, which were common currency elsewhere, especially among the Etruscans; nor would the Greeks have wished to recognize as fellow- Greeks all inhabitants of what we now call Greece, since they identified among the population of the islands and coasts strange remnants of earlier peoples, generically called ‘Pelasgians’ or ‘Tyrsenians’; besides, the Greek-speakers were themselves moving outwards from the Aegean and Peloponnese towards Asia Minor, where they would remain for over two and a half millennia, and towards Sicily, Italy and North Africa. How, when and why this great diaspora was created remains one of the big puzzles about the early Iron Age Mediterranean. What is certain is that it transformed the area, bringing goods and gods, styles and ideas, as well as people, as far west as Spain and as far east as Syria. The Greeks remembered these movements of people and things by way of often complex and contradictory tales of ancient ancestors who spread their seed across the Mediterranean: whole peoples at times reportedly boarded ships to be carried across distances of many hundreds of miles.
‘Carthage Must Be Destroyed’, 400 BC–146 BC
Authors: Abulafia David
Published: November 2020

While the war between Athens and Sparta for control of the Aegean was at its peak, other conflicts, further to the west, embroiled Greek cities in struggles for their life. Carthage was as significant a naval power in its sector of the Mediterranean as Athens was further to the east. In 415, the Carthaginians were content to look on while the Athenians attacked Syracuse. They could see that the Greeks were divided among themselves and too busy squabbling to turn their attention against the Phoenician trading stations on Sicily. From their point of view, anything that weakened Greek power in Sicily was welcome. On the other hand, the destruction of the Athenian forces posed a new problem, to which they found themselves responding rapidly. Not for the first time the Syracusans threatened to dominate the island. However, the real troublemakers proved once again to be the Elymian inhabitants of Segesta, who, not content with the havoc they had wreaked by calling in the Athenians, now appealed to Carthage for help against their old rivals, the Greeks of Selinous. The Carthaginians had good reason to support Segesta. It lay in an area dotted with Punic, that is Phoenician, colonies, notably Panormos (Palermo) and Motya. When in 410 the Segestans offered to become dependants of Carthage in return for protection, the Carthaginian assembly realized that the time had come to consolidate their city’s hold on western Sicily. The Segestan appeal marked a decisive moment in the transformation from a loose confederation of allies and trading stations presided over by Carthage to a Carthaginian empire that included among its subjects not just fellow-Phoenicians but subject peoples – ‘Libyans’, as the Berbers of North Africa were called by Greek writers, Elymians, Sikels and Sikans in Sicily, not to mention Sards and Iberians. There were other, personal factors at work among the Carthaginian elite, for the city was at this time controlled by a group of powerful dynasties that dominated its Senate. A prominent Carthaginian with the common name Hannibal is said to have conceived a passionate hatred for all Greeks after his grandfather Hamilcar was killed in battle against the Syracusan army at Himera in 480 BC.
‘Our Sea’, 146 BC–AD 150
Authors: Abulafia David
Published: November 2020

The relationship between Rome and the Mediterranean was already changing significantly before the fall of Carthage and of Corinth. This relationship took two forms. There was the political relationship: it was clear before the Third Punic War that the Roman sphere of influence extended to Spain in the west and to Rhodes in the east, even when the Roman Senate did not exercise direct dominion over the coasts and islands. Then there was the commercial relationship that was creating increasingly close bonds between Rome’s merchants and the corners of the Mediterranean. Yet the Senate and the merchants were distinct groups of people. Like Homer’s heroes, Roman aristocrats liked to claim that they did not sully their hands in trade, which they associated with craft, peculation and dishonesty. How could a merchant make a profit without lies, deception and bribes? Rich merchants were successful gamblers; their fortune depended on taking risks and enjoying luck. This condescending attitude did not prevent Romans as eminent as the Elder Cato and Cicero from commercial dealings, but naturally these were effected through agents, most of whom were Romans in a new sense. As it gained control of Italy, Rome offered allied status to the citizens of many of the towns that fell under its rule, and also established its own colonies of army veterans. ‘Romanness’ was thus increasingly detached from the experience of living in Rome and, besides, only part of the population of the city counted as Roman citizens, with the right to vote, a right denied to women and to slaves. There may have been about 200,000 slaves in Rome around 1 BC , about one-fifth of the total population. Their experience forms an important part of the ethnic history of the Mediterranean. Captives from Carthage and Corinth might be set to work in the fields, having to endure a harsh existence far from home, ignorant of the fate of their spouses and children. Iberian captives were put to work in the silver mines of southern Spain, in unspeakable conditions.
The View through the Russian Prism, 1760–1805
Authors: Abulafia David
Published: November 2020

The increasing debility of the Ottoman Empire brought the Mediterranean to the attention of the Russian tsars. From the end of the seventeenth century Russian power spread southwards towards the Sea of Azov and the Caucasus. Peter the Great sliced away at the Persian empire, and the Ottomans, who ruled the Crimea, felt threatened. For the moment, the Russians were distracted by conflict with the Swedes for dominion over the Baltic, but Peter sought free access to the Black Sea as well. These schemes had the flavour of the old Russia Peter had sought to reform, just as much as they had the flavour of the new technocratic Russia he had sought to create. The idea that the tsar was the religious and even political heir to the Byzantine emperor – that Muscovy was the ‘Third Rome’ – had not been swept aside when Peter established his new capital on the Baltic, at St Petersburg. Equally, the Russians could now boast hundreds of vessels capable of challenging Turkish pretensions in the Black Sea, even if they were far from capable of mounting a full naval war, and the ships themselves were badly constructed, notwithstanding Peter the Great’s famous journey to inspect the shipyards of western Europe, under the alias Pyotr Mikhailovich. In sum, this was a fleet that was ‘poor in discipline, training, and morale, unskilful in manoeuvre, and badly administered and equipped’; a contemporary remarked that ‘nothing has been under worse management than the Russian navy’, for the imperial naval stores had run out of hemp, tar and nails. The Russians began to hire Scottish admirals in an attempt to create a modern command structure, and they turned to Britain for naval stores; this relationship was further bolstered by the intense trading relationship between Britain and Russia, which had continued to flourish throughout the eighteenth century while England’s Levant trade withered: in the last third of the eighteenth century a maximum of twenty-seven British ships sailed to the Levant in any one year, while as many as 700 headed for Russia.
The Greek and the unGreek, 1830–1920
Authors: Abulafia David
Published: November 2020

An important feature of the Fifth Mediterranean was the discovery of the First Mediterranean, and the rediscovery of the Second. The Greek world came to encompass Bronze Age heroes riding the chariots described by Homer, and the Roman world was found to have deep roots among the little-known Etruscans. Thus, during the nineteenth and early twentieth centuries entirely new perspectives on the history of the Mediterranean were opened up. An early lead was given by the growth of interest in ancient Egypt, discussed in the previous chapter, though that was closely linked to traditional biblical studies as well. In the eighteenth century, the Grand Tour introduced well-heeled travellers from northern Europe to classical remains in Rome and Sicily, and Englishmen saw it as an attractive alternative to time spent at Oxford or Cambridge, where those who paid any attention to their studies were more likely to be immersed in ancient texts than in ancient objects. On the other hand, aesthetic appreciation of ancient works of art was renewed in the late eighteenth century, as the German art historian Winckelmann began to impart a love for the forms of Greek art, arguing that the Greeks dedicated themselves to the representation of beauty (as the Romans failed to do). His History of Art in Antiquity was published in German in 1764 and in French very soon afterwards, and was enormously influential. In the next few decades, discoveries at Pompeii and Herculaneum, in which Nelson’s cuckolded host, Sir William Hamilton, was closely involved, and then in Etruria, further enlarged northern European interest in ancient art, providing interior designers with rich patterns, and collectors with vast amounts of loot – ‘Etruscan vases’, nearly all in reality Greek, were shipped out of Italy as the Etruscan tombs began to be opened up. In Greece, it was necessary to purchase the consent of Ottoman officials before excavating and exporting what was found; the most famous case, that of the Parthenon marbles at the start of the nineteenth century, was succeeded by other acquisitions for northern museums: the Pergamon altar was sent to Berlin, the facings of the Treasury of Atreus from Mycenae were sent to the British Museum, and so on.
Genesis of Statins
Authors: Li Jie Jack
Published: November 2020

As evidence grew that high blood cholesterol levels were linked to heart disease, scientists in both academia and industry began to look for drugs to lower cholesterol as early as the 1950s. Before Akira Endo discovered the first statin, mevastatin, in the 1970s, many things, including hormones, vitamins, and resins, were tried to lower cholesterol. Some worked, and some did not. Thyroid hormone was one of the fi st drugs used for that purpose. The cholesterol-lowering properties of dextro-thyroxine were discovered by serendipity. At one point, surgical removal of part of the thyroid gland had been used to relieve angina, the pain brought on by exercise in coronary artery disease. Doctors observed that thyroid removal also raised the blood cholesterol level, which in turn sped up arterial degeneration. By deduction, the doctors reasoned that taking thyroid hormone should then decrease blood cholesterol levels. Initial clinical trials proved this theory, and dextro-thyroxine was used to lower cholesterol beginning in the 1950s, when thyroid extract became a standard treatment for hypercholesterolemic (high cholesterol) patients. Unfortunately, too much thyroid hormone made patients tremble all the time. Later, a large-scale, long-term clinical trial named the “Coronary Drug Project” established the association of dextro-thyroxine with ischemic heart disease as a severe side eff ect in men. As a consequence, thyroid hormone treatment was discontinued. Women, in contrast to men, enjoy natural cardiac protection through the action of the female sex hormones, the estrogens. In 1930, a minute quantity of estrogen was isolated from the ovaries of 80,000 sows. In the 1950s, reports appeared that estrogen could lower blood cholesterol levels even more effectively than nicotinic acid, another anticholesterol drug used at the time. Unfortunately, men on estrogen for too long began to develop feminine traits, including breast enlargement and loss of libido, and other side effects, although they did acquire relative immunity from heart attacks until late in life. Due to the lack of safe and effiicacious drugs, some doctors seemed willing to take their chances with estrogens.
Disorders of Neuromuscular Transmission
Authors: Wong Agnes
Published: November 2020

Myasthenia gravis is the most common disorder affecting the neuromuscular junction (incidence: 5 per 100,000). Ocular involvement accounts for initial complaints in 75% of patients. Of patients presenting with ocular myasthenia, 50–80% eventually develop generalized myasthenia, usually within two years of onset. Myasthenia gravis is an autoimmune disease caused by the presence of antibodies against acetylcholine receptors, which leads to decreased number of available receptors (usually less than one-third that of normal). It is associated with other autoimmune diseases, including thymoma, dysthyroidism, sarcoidosis, pernicious anemia, aplastic anemia, and collagen vascular diseases (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, ulcerative colitis, Sjögren’s syndrome). ■ Side effects: cholinergic (e.g., bradycardia, angina, bronchospasm) ■ Steps for performing Tensilon test: 1. Prepare 10 mg/mL Tensilon in a tuberculin syringe, 0.6 mg atropine in a tuberculin syringe, and 10 mL normal saline. 2. Establish intravenous access using butterfly needle; flush with 1 mL normal saline. 3. Inject 0.2 mL Tensilon, flush with 1 ml normal saline, and wait 1 min for possible side effects. 4. Inject 0.6 mL Tensilon, flush with 1 mL normal saline, then attach atropine syringe. 5. Wait 3 min; improvement of ptosis or diplopia constitutes a positive test. Improvement of ptosis after application of ice for 2 min on the ptotic eyelid constitutes a positive test. The ice test is especially useful for very young, elderly, or ill patients. Improvement of ptosis or ocular alignment after 30–45 min of sleep constitutes a positive test. ■ Repetitive nerve stimulation with supramaximal stimuli delivered at 2–3 Hz: Rapid decrement of the amplitude of compound muscle action potentials (CMAPs) ≥10–15% confirms the diagnosis in 95% of cases. ■ Single-fiber electromyography (EMG; e.g., frontalis muscle) is highly sensitive (88–99% sensitivity). A positive test consists of increased jitter (increased latency between nerve stimulation and action potential of muscle fibers) and increased blockage (response failure). Acetylcholine receptor antibody is not detectable in about 15% of patients. Muscle-specific kinase is detected in 20% patients who have no acetylcholine receptor antibody and is usually detected in patients with generalized myasthenia gravis.
Invisibility Steals the Seen: Chemistry Creates Criminal Opportunities
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

The Invisible Man and Jekyll and Hyde movies share many features. One of the more interesting chemical threads is that the Hyde formula and the invisibility drug accumulate more realistic drug-like properties with every adaptation. For instance, in the earliest Jekyll and Hyde films, the effects of the transformative formula are permanent until the antidote is taken or is psychologically triggered. Jump forward to the 1960 version starring Paul Massie, and the injected drug doesn’t cause an immediate transformation and its effect wears off after four days. We can infer that Jekyll spontaneously reverts to Hyde because the compound is metabolized in the bloodstream just like any other drug by a process called pharmacokinetics. Once a drug is in the bloodstream, it must travel to its “site of action,” or receptor, before it can exert its effect. This process is called pharmacodynamics. In the 1960 version of Jekyll and Hyde, for example, the receptors must be skin and hair follicles since the transformation causes the facial hair to disappear, the skin to gain color, and the facial skin to tighten so much that Hyde now smiles. The injected compound is dispersed throughout the circulatory system by the pumping of the heart such that the average concentration of the compound rises to a certain value. When the concentration rises above the pharmacological threshold concentration, enough of it is bound to its targeted receptor that it elicits a physiological response. The invisibility effect wears off after a few hours in The Invisible Woman (1940) and The Invisible Agent (1942). Prior to those versions and in the 2000 version, invisibility was portrayed as being permanent. The two films from the 1940s were produced by Universal Studios, which produced many of the classic horror films of the 1930s, including The Invisible Man (1933). Soon thereafter, when Universal revived their monsters for a B movie titled House of Dracula (1945), the benign physician Dr. Edelman is able to explain each monster’s affliction as the result of a disease that can be cured.
Chemistry in the Movies
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

The authors’ common reaction to chemistry in the movies is encapsulated in the archetype movies. These are, first and foremost, great movies that present certain facets of chemistry especially well. They were selected from a much larger group of movies by ranking according to four criteria: (1) contemporary (meaning released after 1970), (2) available on VHS or DVD, (3) included women or other underrepresented groups in significant roles, or (4) was especially favored by one or both of the authors. It became clear from the ranking exercise that older films overcame the criterion of not being recent when they were favored by both authors. We felt they represented the archetype for that chapter and merited special attention. The oldest archetype movie is the 1931 Dr. Jekyll and Mr. Hyde, making it the book’s de facto archetype and reiterating its importance as the book’s overarching theme. Considered as a whole, the five chapters on the “dark side” show chemists, sociopaths, chemical companies, and pleasure seekers making one-sided decisions that ultimately harm themselves and society. After Jekyll becomes addicted to his Hyde formula, he commits acts of personal terrorism and then murder. Griffin works alone to isolate his invisibility formula because he seeks fame, wealth, and power. Once he knows those things are within his grasp, it drives him mad to the point that he commits mass murder. Dr. Mabuse isn’t a chemist, but he is already insane when he commands his army of thugs to engage in acts of chemical sabotage. He wants to begin a “reign of terror.” Reporter Jason Brady learns that a president knows his chemical company produces a toxin that kills his workers and the children living near the plant. He won’t stop production because it would deprive the community of employment. Finally, television director Paul Groves takes his first LSD trip to get in touch with his feelings. While under the influence, he flees the apartment of a guide who was there to ensure he had a good experience. “Bright side” chemists usually work in teams and rely on other people for critical input—they are engaged with society.
Pathogenesis, Epidemiology, and Natural Course of Retinal Detachment
Authors: Brinton Daniel A. , Wilkinson Charles P.
Published: November 2020

Retinal detachment does not result from a single, specific disease; rather, numerous disease processes can result in the presence of subretinal fluid. The three general categories of retinal detachments are termed rhegmatogenous, exudative, and tractional. Rhegmatogenous detachments are sometimes referred to as primary detachments, while both exudative and tractional detachments are called secondary or nonrhegmatogenous detachments. The three types of retinal detachments are not mutually exclusive. For example, detachments associated with proliferative vitreoretinopathy or proliferative diabetic retinopathy may exhibit both rhegmatogenous and tractional features. However, excluding the section on differential diagnosis in Chapter 5, the scope of this book is limited to rhegmatogenous retinal detachments. Accordingly, throughout the book, the term retinal detachment refers to the rhegmatogenous type, unless another type is specifically mentioned. Rhegmatogenous detachments (from the Greek rhegma, meaning rent, rupture, or fissure) are the most common form of retinal detachment. They are caused by a break in the retina through which fluid passes from the vitreous cavity into the subretinal space. The responsible break(s) can be identified preoperatively in more than 90% of cases, but occasionally the presence of a minute, unseen break must be assumed. Exudative detachments, also called serous detachments, are due to an associated problem that produces subretinal fluid without a retinal break. This underlying problem usually involves the choroid as a tumor or an inflammatory disorder. Tractional detachments occur when pathologic vitreoretinal adhesions or membranes mechanically pull the retina away from the pigment epithelium without a retinal break. The most common causes include proliferative diabetic retinopathy, cicatricial retinopathy of prematurity, proliferative sickle retinopathy, and penetrating trauma. Retinal breaks may subsequently develop, resulting in a combined tractional and rhegmatogenous detachment. The essential requirements for a rhegmatogenous retinal detachment include a retinal break and low-viscosity vitreous liquids capable of passing through the break into the subretinal space. Vitreous changes usually precede development of important defects in the retina. The usual pathologic sequence causing retinal detachment is vitreous liquefaction followed by a posterior vitreous detachment (PVD) that causes traction at the site of significant vitreoretinal adhesion with a subsequent retinal tear. Fluids from the vitreous cavity then pass through the tear into the subretinal space (Figure 2–1), augmented by currents within the vitreous cavity caused by rotary eye movements. Although a total PVD is usually seen, many detachments occur with partial vitreous detachment, and evidence of posterior vitreous detachment may not be seen.
Pneumatic Retinopexy
Authors: Brinton Daniel A. , Wilkinson Charles P.
Published: November 2020

Pneumatic retinopexy (PR) is an office-based, sutureless, no-incision alternative to scleral buckling or vitrectomy for the surgical repair of selected retinal detachments. Cryotherapy is applied around the retinal break(s) to form a permanent seal. A gas bubble is injected into the vitreous cavity, and the patient is positioned so that the bubble closes the retinal break(s), allowing resorption of the subretinal fluid (Figure 8–1A–F). As an alternative to cryotherapy, laser photocoagulation can be applied after the intraocular gas has caused the retina to reattach. Sulfur hexafluoride (SF6) is the gas most frequently used with pneumatic retinopexy. Perfluorocarbon gases such as perfluoropropane (C3F8) are sometimes used, and success has also been reported with sterile room air. In selecting a gas, it is important to understand the longevity and expansion characteristics of the gases. SF6 doubles in volume within the eye, reaching its maximum size at about 36 hours. It will generally disappear within about 10–14 days, depending on the amount injected. Perfluoropropane nearly quadruples in volume, reaching maximum size in about three days. The bubble will last 30–45 days in the eye. Room air does not expand, but immediately starts to reabsorb. The air bubble will be gone within just a few days (Table 8–1). The initial expansion of SF6 and C3F8 is due to the law of partial pressures and the solubility coefficients of the gases involved. A 100% SF6 bubble injected into the eye contains no nitrogen or oxygen, but these gases are dissolved in the fluid around the bubble. Due to the law of partial pressures, nitrogen and oxygen will diffuse into the gas bubble. SF6 also starts to diffuse out of the gas bubble into the surrounding fluid which contains no SF6. However, nitrogen and oxygen diffuse across the gas–fluid interface much more quickly than SF6 because of the relative insolubility of SF6. The net result is an initial influx of gas molecules into the bubble, expanding its size until partial pressures equilibrate, net influx equals net egress, and maximum expansion is reached. Then the bubble gradually reabsorbs as the SF6 is slowly dissolved in the surrounding fluid.
Reconstruction of the Lower Eyelid
Authors: John Park D.J. , Harrison Andrew
Published: November 2020

The lower eyelid, tethered medially and laterally by the canthal tendons, is normally suspended at the level of the inferior limbus with the aid of orbicularis tone counterbalanced by the force of the lower eyelid retractors and gravity. The lower eyelid is apposed to the globe because of the posterior position of the canthal tendon insertions relative to the projection of the globe. Disruption of the normal anatomic relationships from trauma or inflammatory disease or as a result of surgical resection of tumors can result in a poorly functioning lower eyelid with poor cosmesis. The lower eyelid has been conceptualized as consisting of three layers or lamellae. The anterior lamella is composed of skin and orbicularis muscle; the middle lamella is composed of the lower eyelid retractor (capsulopalpebral fascia) and fat; and the posterior lamella is composed of tarsus and conjunctiva. One or more of the lamellae may be disrupted following trauma or tumor resection, and each layer must be addressed in order to reconstruct a normal-appearing and -functioning lower eyelid. Imbalance of tension at the anterior and posterior lamellae, especially in the setting of lower eyelid laxity, can result in malrotation of the eyelid margin, causing entropion or ectropion. For example, inflammation and scarring of the conjunctiva from Stevens-Johnson syndrome or ocular cicatricial pemphigoid will produce entropion, whereas contraction of vertical cutaneous scar or ichthyosis will cause ectropion. A balance of tension of the lamellae must be maintained during reconstruction of the lower eyelid in order to prevent secondary malrotation. Disruption of normal anatomy as often seen following trauma can be addressed by reapproximation of the disrupted segments to their normal anatomic positions. Only rarely will trauma to the lower eyelid result in loss of tissue. Reconstruction with local flaps or free grafts is occasionally needed in traumatic cases that present in a delayed fashion. Local flaps and free grafts are needed to fill and reconstruct a defect in the lower eyelid, a situation that most often presents following resection of tumor.
Surgical Decompression of the Orbit
Authors: Perry J.D. , Lewis Craig
Published: November 2020

In 1835 Graves first described the characteristic exophthalmos of thyroid eye disease, and his name has since become synonymous with thyrotoxic ophthalmopathy. Graves disease is relatively common, with a prevalence and incidence of 1% and 0.1%, respectively. Although subtle signs of ophthalmopathy are present in most patients with Graves disease, only 30% have obvious eye findings, and only 5% develop ophthalmopathy severe enough to warrant specific treatment with radiotherapy, immunosuppression, or orbital decompression surgery. Graves disease and Graves ophthalmopathy are more common in females than in males, though males tend to have more severe eye disease. Cigarette smokers have an increased risk of developing Graves disease, an increased risk of developing associated ophthalmopathy, and a progressively increased risk of severe ocular manifestations. While the onset of Graves disease usually occurs when people are in their forties, thyroid optic neuropathy tends to occur in the fifties and sixties, underscoring the importance of careful long-term follow-up of these patients. The ophthalmopathy of Graves disease is usually associated with hyperthyroidism, but it occurs in euthyroid and hypothyroid patients as well. The clinical course of the ophthalmopathy does not directly correlate with the thyroid status, although more than 80% of thyroid patients who develop severe ophthalmopathy do so within 18 months of the detection of the thyroid disease. The early findings of thyroid ophthalmopathy include conjunctival injection, lacrimation, ocular surface irritation, orbital and periorbital swelling, and mild eyelid retraction. Progression of the disease can result in severe orbital congestion, massive enlargement of the extraocular muscles with secondary diplopia, proptosis, compressive optic neuropathy, prominent eyelid retraction, spontaneous subluxation of the globe anterior to the eyelids, and exposure keratopathy. Treatment options for these serious complications of Graves disease include systemic corticosteroids, radiation therapy, and orbital decompression surgery. The role of radiation therapy in the management of Graves ophthalmopathy remains controversial. In 1973, Donaldson et al. first reported results of radiotherapy for Graves ophthalmopathy using a megavoltage linear accelerator. This series and multiple subsequent series have reported favorable results in approximately 60% of patients.
Soft Tissue Fillers for Facial Aesthetics
Authors: Jordan David R. , Klapper Stephen R.
Published: November 2020

The search for an ideal soft tissue filler to correct facial folds and wrinkles has gone on for at least 100 years. Many products have been tried, including mineral oil, paraffin, and liquid silicone, in an effort to improve soft tissue imperfections. Most of the early substances were abandoned due to a high incidence of complications, including chronic edema, granuloma formation, scarring, and ulceration. The ideal tissue filler should be biocompatible, noncarcinogenic, nonteratogenic, nonmigratory, and free of adverse reaction. The ideal filler should also be inexpensive and easy to use, require little preparation, and provide long-lasting, natural, and predictable results with minimal recovery time. Although no currently available injectable substance possesses all of these ideal attributes, many currently available products provide more-than-satisfactory results and have excellent safety profiles. The indications for injectable filler agents have largely evolved through a better understanding of facial aging, specifically soft tissue deflation typically noted between youth and middle age. The limitations of surgical procedures to correct soft tissue atrophy, as well as the possibility of delaying surgical procedures by early intervention with injectable fillers, have made these agents very valuable in improving the appearance of the aging face. With the continued improvement in products and techniques during recent years, the clinical results with fillers have become more predictable. As a result of this improvement, an increasing number of patients are seeking nonsurgical methods for correcting age-related changes to their facial skin and soft tissue. There are essentially two types of natural facial wrinkles (or rhytides): dynamic and static. They may occur separately or in combination. Dynamic wrinkles appear within the skin due to repeated contracture by the underlying muscles of facial expression. Static wrinkles are present regardless of facial dynamics and result from intrinsic changes in the components of the dermal ground substance and from extrinsic factors such as smoking, gravity, and sun exposure. The formation of both dynamic and static wrinkles is influenced by the quality of the natural collagen matrix within the dermal layers of the skin. For the most part, dynamic wrinkles are best treated with Botulinum toxin injections, particularly in the upper face.
Cognitive and Behavioral Aspects of Congenital Adrenal Hyperplasia
Authors: Berenbaum Sheri A.
Published: November 2020

Congenital adrenal hyperplasia (CAH) is a family of genetic disorders involving enzyme defects in the synthesis of cortisol in the adrenal gland (for reviews and additional information, see Grumbach, Hughes, and Conte 2003; Merke and Bornstein 2005; Speiser 2001). The most common defect is in 21-hydroxylase (21-OH), which accounts for 90% of cases of CAH and results in physical signs of androgen excess. Congenital adrenal hyperplasia is heterogeneous, with the phenotype usually classified as nonclassic (NC), a mild, often late-onset form, or classic, a severe form. Classic CAH consists of the salt-wasting (SW) and simple-virilizing (SV) forms, which reflect degree of aldosterone deficiency (mineralocorticoid disturbance), with a SW:SV ratio of approximately 2:1. It is likely that the three forms of CAH (NC, SV, SW) reflect an underlying continuum. Individuals with classic CAH due to 21-OH deficiency are unable to produce enough cortisol to suppress the release of adrenocorticotropic hormone (ACTH). This results in an accumulation of cortisol precursors, leading to increased production of androgen from the adrenal gland beginning early in gestation and continuing until the disorder is diagnosed and treated with cortisol replacement, usually in the newborn period. Classic CAH is usually detected through newborn screening in the United States and in some other countries (Therrell 2001). Untreated classic CAH causes rapid growth (and ultimately short stature), precocious puberty, and physical virilization. Aldosterone deficiency can cause hypoglycemia, and potentially life-threatening episodes of hyponatremia and hyperkalemia. The defects in CAH also have consequences for behavior and cognition, as will be discussed throughout this chapter. Individuals with nonclassic CAH due to 21-OH deficiency do not have the significant cortisol deficiency characteristic of classic CAH. Nevertheless, they do have increased androgen, usually beginning in childhood or in adulthood. The excess androgen is associated with an increased likelihood of early puberty, infertility, and in women, hirsutism, menstrual irregularities, and polycystic ovaries. Classic CAH is one of the most common inborn errors of metabolism and the most common cause of ambiguous genitalia. Data from newborn screening show the incidence to be approximately 1 in 15,000 live births with some variations across countries and ethnic groups (Therrell 2001).
Behavioral and Cognitive Manifestations of Celiac Disease
Authors: Niederhofer Helmut , Pittschieler Klaus
Published: November 2020

Celiac disease (CD) is an immune-mediated chronic inflammatory disorder characterized by permanent gluten intolerance in genetically susceptible individuals. Exposure to gluten perpetuates an enteropathy leading to malabsorption with chronic diarrhea, weight loss, and abdominal distension. The small intestine mucosa is abnormal, and jejunal biopsy demonstrates various degrees of villous atrophy, absence of surface mucosa, and crypt hyperplasia. The diagnosis is based on the demonstration of a more or less pronounced villus atrophy in a jejunal biopsy. The villous atrophy improves after withdrawal of gluten from the diet. If undetected or neglected, CD may cause considerable late complications from malabsorption or secondary autoimmune diseases (Feigbery 1999; Maki and Collins 1997; Holmes 1996). The therapy consists of permanently excluding gluten from the diet and allows the healing of the mucosal lesion. Abnormalities of humeral and cell-mediated immunity suggest that celiac disease is an immunologic disorder (Walker-Smith 1996). It is caused by inappropriate immune response to the gliadin component in the dietary gluten (Dieterich 1997). Genetic susceptibility is present, and 90% of the patients have HLA DRG 3 DQ-2 haplotype, and some have the HLA DR4 DQ8 gene (Hadjivassiliou 1998). A close relationship exists between the biochemical properties of tissue transglutaminase and the basic molecular mechanisms responsible for CD, and possibly with the neuropsychiatric manifestations of CD (Gentile 2002). Anti–tissue transglutaminase antibody assay has been used as a serologic screening test for CD. In addition, antiendomysial, antigliadin, and antireticulin antibodies are associated with the disease. Nevertheless, the clinical symptomatology affecting the gastrointestinal (GI) system, histological abnormalities on gut biopsy, and presence of antiendomysial antibodies do not always coexist. Also, presentation with minor symptoms, such as irritable bowel syndrome, anaemia, slight weight loss, and fatigue, has become increasingly common, and in many cases the disease may be clinically silent, despite manifest small-bowel mucosal lesions. Therefore, CD is underdiagnosed (Catassi et al. 1996; Feigbery 1999; Holmes 1996; Kolho et al. 1998; Maki and Collins 1997).