In its broadest sense, ophthalmia is an inflammation of the eye, especially of the conjunctiva of the eye. The term derives from the Greek word ophthalmos (the eye). Hence, almost any disease that attacked the eye was called ophthalmia in many Greco- Roman and later European sources until the beginning of the twentieth century. As medical knowledge was refined, defining terms were attached, such as “purulent ophthalmia,” “neonatorum ophthalmia,” or “Egyptian ophthalmia.” The problem for historians attempting to define eye diseases in the past is that the term “ophthalmia” meant many diseases that attack the eyes or that manifest symptoms in the eye, and that blindness due to “ophthalmia” had many causes. Two important causes of ophthalmia were trachoma and conjunctivitis; this essay is limited to these.

Trachoma (also called granular conjunctivitis and Egyptian ophthalmia) has been defined as a contagious keratonconjunctivitis caused by Chlamydia trachomatis (serotypes A, B, Ba, and C). It is characterized by the formation of inflammatory granulations on the inner eyelid, severe scarring of the eye in the fourth stage, and blindness (but not in all cases). It was one of the leading causes of blindness in the past, and still blinds millions in Asia, the Middle East, and Africa (Bietti and Werner 1967; Rodger 1981; Insler 1987).

Conjunctivitis (purulent ophthalmia) may appear with trachoma and may complicate the progression of the disease so that blindness rather than healing occurs. Although conjunctivitis may denote any inflammation of the conjunctiva (“the mucous membrane lining the inner surface of the eyelids and covering the frontpart of the eyeball”), bacteria often infect the conjunctiva at the same time as does trachoma, thus causing an acute bacterial conjunctivitis.

Textbooks on tropical diseases in Africa are well out of date. With the recognition of new and deadly viral infections – Lassa, Marburg, Ebola, Congo–Crimean Hemorrhagic Fever, Rift Valley Fever, and AIDS – the classical descriptions of major diseases such as malaria and yellow fever must be thoroughly revised, and to the roster of more minor ailments can be added dengue, Chikungunya, O’Nyong Nyong, West Nile fever, and others. One must be ready to challenge earlier descriptions of African fevers in general. Malaria in particular has been an “umbrella” diagnosis, which obscured and still obscures the diagnosis of other, sometimes dangerous concomitant illnesses in regions where malaria itself is endemic to hyperendemic. The absolute need for laboratory confirmation to support the clinical impression is slowly being recognized. This must extend beyond the simple demonstration of presence of malaria parasites in the blood. Malaria parasites in the blood certainly prove that the individual in question harbors the parasite. But it is not necessarily proof that the actual immediate infection from which the individual is suffering is related to the existing chronic malarial position. Treatment of the malarial infection is indicated, and is followed almost universally in tropical Africa, with or without confirmation of the presence of malaria parasites. The first diagnosis entertained for all of the viral infections listed above is almost always “malaria.”

It is when the patient does not respond to the antimalarial therapy exhibited that other possible diagnoses are considered. In addition to the viral possibilities, the list should also include influenza, typhoid fever, various rickettsioses, leptospiral infections, bacterial and viral enteropathogenic agents – indeed the range of infections capable of inducing a febrile response.

Sexual “deviance” is technically any deviation from the sexual norm. Sexual disease, a new diagnostic category in the eighteenth century, was classed as a syndrome and seems in retrospect to have been an iatrogenic one based more on philosophical and moral grounds than on any medical ones. The disease entity, however, was fitted into some of the medical theories of the time, and as these theories were challenged and undermined, modifications were made in order to justify maintaining certain forms of sex behavior in the category of disease.

In recent decades much of the sexual behavior previously classed as disease has been removed from that category. This redefinition has been based on a better understanding of sexual behavior. It has also been a result of the protests of some groups who reject being classed as ill or sick and having their behavior categorized as pathological, emphasizing the iatrogenic component of the disease. Nonetheless, efforts are being made to maintain other kinds of sexual activity under the rubric of disease. Generally, these are activities that are regarded as unacceptable by society or viewed as compulsive behavior maintain the classification as a way of justifying their intervention or of promising a cure.

Medical Background

Though physicians throughout recorded history have been interested in diseases and infirmities that affect sexual performance, the concept that certain forms of sexual behavior constitute a disease in and of themselves is a modern phenomenon. It also seems to be restricted to western Europe and people and cultures descended from or influenced by western European culture.

Trichinosis, also known as trichinellosis, trichiniasis, or trichinelliasis, is a disease of humans and of other mammals infected with the nematode worm Trichinella spiralis. The pathological changes and the symptomatology of Trichinella infection are manifestations of three successive stages in the life history of the worm: (1) penetration of adult female worms into the intestinal mucosa, (2) migration of juvenile worms, and (3) penetration of juvenile worms and subsequent encystment in muscle cells.

Distribution and Incidence

Although trichinosis occurs worldwide, in humans it is found principally in the United States, Canada, and eastern Europe. It is also well known in Mexico, parts of South America, Africa, southern Asia, and the Middle East. People acquire trichinae by ingesting uncooked or poorly cooked meat, especially pork. Home-made sausages have caused many recent outbreaks in the United States. Hence, the prevalence of trichinosis is less in the tropics and subtropics, where less meat is consumed. Trichinosis does not occur among Hindus, Jews, and Moslems, for whom there are religious bans on eating pork.

Although the prevalence of trichinosis in human populations is low (probably 2.2 percent or less in the United States, based on autopsy surveys), epidemic outbreaks are not infrequent. Incidence of infection is likely to be higher than suspected because of the vagueness of symptoms, which usually suggest other conditions.

Syphilis or, more properly, venereal syphilis is a chronic communicable disease, which, until the acquired immunodeficiency syndrome emerged in the early 1980s, was the most serious and dreaded of the so-called sexually transmitted diseases (STD) – formerly, venereal diseases (VD). Caused by Treponema pallidum subspecies pallidum, a spirochetal bacterium, the only known natural host of which is the human being, venereal syphilis is thus one of the human treponematoses – along with pinta, yaws, and endemic syphilis. Although predominantly transferred by sexual contact, T. pallidum is also capable of being transmitted from an infected mother to her fetus across the placenta at any stage of pregnancy (congential syphilis).

Syphilis develops naturally through three clinical stages (primary, secondary, and tertiary or late), each separated by a subclinical period. Of the subclinical periods, the one between the secondary and tertiary stages (latent syphilis) is the most pronounced. Clinical manifestations of syphilis are extremely protean, and capable, at the tertiary stage, of affecting any system of the human body.

Syphilis took its name from Girolamo Fracastoro’s well-known poem, Syphilis, sive morbus gallicus (1530), in which the Italian humanist-physician invented this phrase to name the disease then known all over Europe as morbus gallicus. However, the term syphilis did not become widely used until the late eighteenth century, and that usage was vague and applied to many other symptoms besides those of venereal syphilis until the development of the germ theory in the late nineteenth and early twentieth centuries.

The agent of this disease, the sporozoan protozoan Toxoplasma gondii, is a common parasite of many species of birds and mammals. The organism was first seen in 1908 in the tissues of a Tunisian rodent, the gundi, and fully described in 1909. Human disease was first described in 1923 and congenital neonatal disease was reported in 1939, but the complex life cycle of the parasite was not elucidated until 1970. Serologic tests show that humans around the world harbor T. gondii, but because almost all infections are asymptomatic, very few have the disease. The protozoan is an intracellular parasite of a variety of tissues in warm-blooded vertebrates. It multiplies by binary fission in a host cell, eventually rupturing the cell and releasing parasites to attack other cells. Sexual reproduction can take place only in cats and other felines. These definitive hosts release oocysts, the stage infective for herbivores, in their feces. Asexual intracellular replication takes place in the herbivore, and, if the tissues containing T. gondii are eaten by a carnivore, asexual reproduction may also occur in their tissues. Humans can become infected by eating poorly cooked or raw meat or poultry, by ingesting oöcytes from the feces of cats, or congenitally.

Clinical Manifestations

Human infections are usually inapparent, although they sometimes can lie dormant for years and flare up in weakened or immunodeficient hosts. Most cases in otherwise healthy people are mild and cause vague symptoms like fever and weakness. The disease often mimics infectious mononucleosis. Chronic cases can cause diarrhea, headache, and eye damage.

Goiter is an ancient disease that has always been more common in some places than in others. Chinese writings show that goiter was known at least by the third century B.C. (Lee 1941) and possibly earlier (Needham et al. 1970). When Juvenal (Decimus Junius Juvenalis), the Roman satirist, wrote, about A.D. 127, “Who is amazed at a swollen neck in the Alps?” he knew that goiter was so much more common there than elsewhere that it should be no surprise.

Terminology

The word “goiter” (or goitre in Europe) derives from the Latin gutter, but the meaning has shifted from “throat” or “neck” to mean specifically an enlarged thyroid gland. An ancient Greek synonym was bronchocele, a term actually used to describe any enlargement in the neck, although it meant literally a swelling or an outpouching of the trachea. Over time this term also came to mean an enlarged thyroid (e.g., the English “bronchocele” of the eighteenth and nineteenth centuries). Modern synonyms are the Spanish bocio (from Latin, botium), the Italian gozzo, and the German Kropf. The ancient Latin word struma was probably originally used to describe inflamed lymph nodes in the neck, most likely tuberculous, but was later used to denote the normal thyroid gland, and is still so used although it is almost obsolete.

Confusion over names is understandable, as the thyroid gland itself was unknown until the sixteenth century. Leonardo da Vinci may have drawn the thyroid about the year 1500, but the drawing was not published until much later. Andreas Vesalius did note “laryngeal glands” in 1543, but not in humans.

America north of the Rio Grande, that life zone sometimes referred to as the Nearctic region, presents the scholar of history and geography of disease with numerous challenges. These include such questions as the following: What potential disease-causing agents existed in the hemisphere before the comparatively recent arrival of human beings? How effective was the “cold screen” (Stewart 1960) in ensuring the health of the migrants crossing the link from Eurasia to the New World? Given the isolation of this population, how varied was it in a genetic sense, and how well adapted did it become to North American ecologies? Were native North Americans indeed “far more healthy than any others of whom we know” (Ashburn 1980)? Just what was the impact of the “Columbian exchange” (Crosby 1972)? Did these invaders receive the country “from the hands of nature pure and healthy” (Rush 1786)? What relative contribution to ill health and disease did the European group provide compared to that of the enslaved African populations? What were the dimensions and timing of the “epidemiologic transition” in North America (Omran 1977)? How real have urban and rural differences in health experience been through time? How serious is the threat today of “life-style” diseases?

Clearly all of these and other equally intriguing questions arise. This brief discussion can only hope to touch on some of them and to review a portion of the work by persons from biochemists to medical historians, from archaeologists to medical geographers, who have applied their learning to the fascinating question of human well-being through the ages in North America.

Legionnaires’ disease is an acute infection of humans, principally manifested by pneumonia, that occurs in a distinctive pattern in epidemics and is caused by bacteria of the genus Legionella. Typically the incubation period – the interval between exposure to the bacterium and the onset of illness – is 2 to 10 days, with an average of 5 to 6 days, and the attack rate – the proportion of people exposed to the bacterium who become ill – is less than 5 percent. Without specific antibiotic treatment, 15 percent or more of the cases are fatal, although the percentage of fatal cases rises sharply in immunosuppressed patients.

Legionnaires’ disease is one form of presentation of Legionella infections, which are generally referred to by the umbrella term legionellosis. Another distinctive clinicoepidemiological pattern of legionellosis is Pontiac fever. Pontiac fever affects 45 to 100 percent of those exposed and has an incubation period of 1 to 2 days. Pneumonia does not occur, and all patients recover. More than 20 species of Legionella have been identified, 10 of which are proven causes of legionellosis in humans. The most common agents of human infection are Legionella pneumophila, Legionella micdadei, Legionella bozemanii, Legionella dumoffii, and Legionella longbeachae.

Legionellae are distinguished from other bacteria in being weakly staining, gram-negative, aerobic rods that do not grow on blood agar or metabolize carbohydrates, and have large proportions of branched-chain fatty acids in their cell walls and major amounts of ubiquinones with more than 10 isoprene units on the side chain.

The term “filariasis” refers to several diseases of both humans and animals caused by infection with a specific group of parasitic nematodes called filarial worms (named for the hairlike appearance of the adult form). Those worms that affect humans belong to the Order Filarioidea, Family Dipetalonematidae. They include (1) Wuchereria bancrofti and Brugia malayi, which are common causes of elephantiasis (extreme swelling and skin thickening of the legs, scrotum, labia, or arms) and chyluria (lymph and emulsified fat globules in the urine); (2) Loa loa, the “eye worm”; and (3) Onchocerca volvulus, the cause of onchocerciasis. Depending upon their species, adult filarial worms of both sexes reside in the lymphatic system, subcutaneous tissues, or peritoneal and pleural cavities. Sexual reproduction results in embryos (microfilariae) that enter blood or skin, where they are ingested by a particular intermediate host (certain species of mosquitoes, horse fly, black fly, or other arthropods). The microfilariae develop into larvae in their intermediate hosts and then reenter vertebrate hosts (humans or animals) through bites in the skin made by the intermediate host arthropods. Loa Loa is endemic in West and central Africa, whereas onchocerciasis is found in Mexico, Central America, and West Africa. Discussion of human lymphatic filariasis in the remainder of this entry will be limited to the most prevalent form (90 percent of infections), that caused by W. bancrofti (Sasa 1976; Beaver, Jung, and Cupp 1984; Mak 1987; Manson-Bahr and Bell 1987).

Southeast Asia can be visualized as the part of Asia that spills into the sea, comprised of long coasts, tidal plains, peninsulas, and islands. There are high mountains, inland plains, plateaus, and upland valleys; nonetheless, to a very large degree, human culture has developed with an acute awareness of water, from the sea, the rivers, and the monsoon rains. It is therefore not surprising that many of the endemic health problems in the region are related to water; indeed, since prehistoric times, nearly all major areas of habitation have been exposed to global contact by water transport.

Maritime routes linking the littoral civilizations of the Eurasian landmass have passed through Southeast Asia for more than two millennia. We can accordingly assume that from early times the region experienced all of the epidemic diseases familiar to the ancient world. What inhibits discussion of diseases in the earlier historical periods of Southeast Asia is the lack of data. Because of the prevailing tropical-equatorial climate, the preservation of written records has, until recently, required greater effort than most human societies were prepared to make. Our first information comes from the observations of Chinese annalists, whose works survived in the temperate climate of northern China. As the Chinese moved southward into what is today northern Vietnam, they recorded perceptions of disease associated with what for them were southern lands.

Most prominent among the health problems encountered by ancient Chinese armies in Vietnam were malaria and other “fevers” associated with the monsoon rain season. Chinese generals timed their expeditions into Vietnam to coincide with the dry season, from November to May.

Eclampsia is a puzzling hypertensive disorder affecting only women. Associated solely with pregnancy and childbirth, it is an epileptic form of convulsions that develops during the second half of pregnancy and disappears after conception. The severity depends upon the degree and timing of the illness as well as the characteristics of the patient. Eclampsia is associated with hypertension, edema, and toxemia, and all three can cause the symptoms of the disease to vary widely. Preeclampsia refers to hypertension, abnormal edema, or proteinuria during pregnancy, whereas eclampsia is the disease’s most extreme form, manifested by severe convulsions, coma, and even death. Eclampsia is a leading cause of maternal and fetal mortality and can cause stillbirths or premature labor. Medical experts remain confused about the cause of this disorder and have no effective way to cure the disease other than to terminate pregnancy by delivering the baby. Through careful prenatal care, however, physicians can usually control the problem, and it is now relatively rare in the United States and Europe.

Not only is the disease difficult to define, but also accurate records of its existence are rare, especially in Third World countries where prenatal care by a medical attendant is uncommon. Although eclampsia is one of the diseases most troubling to obstetricians, research on the illness is difficult because it is found only in human beings. Its etiology remains unknown but may be multifactorial.

Several species of the genus Paragonimus, the lung flukes, can parasitize human beings. The most important, Paragonimus westermani, is found in China, Japan, Korea, Southeast Asia, Papua New Guinea, and parts of India and Central Africa. It was first discovered in the lungs of tigers in European zoos in 1878. Other species occur in Asia, in Africa, and in Central America and parts of South America. Wild and domestic members of the cat and dog families and other carnivorous animals are also hosts, and in many places humans are accidental hosts for worms that normally reside in other mammals. Adult worms produce eggs in the lungs, which reach fresh water either in the sputum or by being coughed up, swallowed, and passed in the feces.

Motile larvae hatch, penetrate an appropriate type of snail, undergo two reproductive cycles, and emerge to seek the second intermediate host, a crab or crayfish. Here they penetrate between the joints of the crustacean’s exoskeleton, and encyst there to await ingestion by humans or other definitive host. They then burrow through the intestinal wall and the diaphragm and enter the lungs, where they may survive for many years. Slow, chronic lung damage may become very serious in heavy infestations. Migrating flukes sometimes wander widely lost and reach atypical (ectopic) sites like the brain, where they cause a variety of neurological symptoms and may prove fatal.

Tapeworms are flatworms in the class Cestoda of the phylum Platyhelminthes. The body of an adult worm consists of a small head or scolex, which is usually armed with hooks or suckers to attach the animal to the wall of its host’s small intestine, and a chain of segments or proglottids. New proglottids arise by budding from the scolex region. As they mature, they are pushed away from the head by the formation of new proglottids and develop both male and female sex organs. After fertilization, eggs or gravid proglottids are excreted with the host’s feces. Tapeworm life cycles are complex. In general, the eggs must be ingested by an intermediate host, where they typically become saclike larvae in the tissues. When the host of the adult form (the definitive host) eats an infected intermediate host, adult worms develop in its intestine. Some species have two or more intermediate hosts and can use several species as the definitive host. Serious clinical disease often occurs when a parasite becomes established in an atypical host or when larval forms are able to develop in what is normally a definitive host.

History

Because tapeworms can exceed 30 feet in length and strings of segments are often passed in the feces, it is not surprising that they were described by ancient writers in China, India, and the Mediterranean world. Encysted larvae – bladderworms or cysticerci – have been known in beef and pork for millennia, but their relationship to adult worms was not suspected until the eighteenth century and not proved until 1855, when F. Küchenmeister fed larval pork tapeworms concealed in food to condemned criminals and recovered adult worms on autopsy.

Hepatitis literally refers to any inflammation of the liver. Even when restricted by the term “infectious,” it has many causes, including malaria and many viruses including that of yellow fever. By convention, however, infectious hepatitis usually refers to a small group of diseases caused by several unrelated viruses, whose most obvious and most consistent symptoms are due to liver damage. Because these diseases are unrelated, except in liver involvement, they will be treated individually. Only their early undifferentiated history can be reviewed in general terms.

Even the distinction between infectious and noninfectious hepatitis is a problem. Autoimmune chronic active hepatitis will not be considered here, although there is evidence of viral involvement in triggering the autoimmune reaction. Liver cancer will be included as a late consequence of infection with hepatitis B virus, because that seems to be the main cause. Other clinically similar diseases that are not covered here are cirrhosis due to toxins such as alcohol, and jaundice due to physical obstruction of the bile duct.

History

Until the mid-1900s, hepatitis was frequently equated with jaundice, although jaundice is only a sign of a failure to clear normal breakdown products from the blood. Under this terminology, hepatitis and other liver diseases played a very important role in early medical writings, but it is difficult to determine which references relate to hepatitis as we now know it, and which refer to the various other causes of jaundice. It is even more difficult to distinguish one type of hepatitis from another in the early references.

The Renaissance in European history was a time of political, intellectual, and cultural change that had its origins in Italy during the fourteenth century. Beginning roughly during the lifetime of the poet Francesco Petrarch, who died in 1374, literati began to look to classical Greece and Rome for models of human political behavior and stylistic models of discourse and artistic representation. This humanistic quest involved the energies of philosophers and artists throughout the fifteenth, sixteenth, and seventeen centuries, as Renaissance ideas spread northward. Though narrowly conceived in scholarly and artistic circles, the Renaissance matured in urban settings. Because this time period coincides with technological innovations and the subsequent exploration and conquest of new worlds, we are inclined to associate the issue of Renaissance diseases with both the growth of cities and the age of European discovery. The period also frames the era of recurrent epidemics of bubonic plague in Europe.

Population growth in Europe was steady during the central, or “High,” Middle Ages but did not lead to the growth of large metropolitan centers. Urbanization was earliest and most dramatic in the Mediterranean lands, where city cultures had also been the basis of ancient Roman hegemony. By the late thirteenth century, Florence and Venice, as successful commercial centers, had populations of more than 100,000. Rome, Milan, and Barcelona may have been equally large. Smaller urban areas of 50,000 to 80,000 individuals existed throughout northern Italy and Spain. These cities were roughly twice as large as the “urban” areas of England, including London.

It has been clear to virtually every observer of demographic patterns in the Americas that the differences between Anglo and Latin America are traceable to the differences between the nations that colonized each region, as well as to the characteristics of the indigenous populations of each region. The settlement of North America by the British was a commercial venture, the numerous settlements reflecting the economic and religious diversity of the English Reformation and the growing economic complexity of Britain itself. By contrast, “in Spanish America, the diverse conditions of an entire continent had to find expression in the same set of standard institutions” (Lang 1975).

Moreover, by the sixteenth century the Iberian Peninsula was becoming “underdeveloped” in contrast to the countries of northwestern Europe, including England. Like eastern Europe, it was characterized by large estates worked by a servile peasantry. This pattern was replicated in the Americas, where the Spanish encountered an extensive indigenous agricultural population with whom they established a semifeudal relationship. There was no such indigenous population in the north, and the British either pushed aside or killed those they did encounter. As a result, socioeconomic and settlement patterns differed. With the exception of the southeast, family-owned and -operated farms became the dominant pattern in English America. In most of Latin America, haciendas and plantations became the dominant pattern. In the areas where an extensive agricultural society was conquered, Indians provided the servile labor force. Elsewhere, primarily in the Caribbean islands and in what became Brazil, slaves imported from Africa provided the servile labor force on plantations originally devoted to sugar growing.

Classification

Gallstones are quite common in modern populations, occurring in nearly 20 percent of autopsies. Though often asymptomatic, they can produce significant morbidity, leading to cholecystitis, cholangitis, biliary cirrhosis, and pancreatitis.

The chief constituents of gallstones are cholesterol, bilirubin, and calcium. Other components may include fatty acids, triglycerides, protein, and polysaccharides. Descriptively, there are four major types of gallstones: (1) pure cholesterol stones; (2) mixed stones composed of cholesterol, bilirubin, and calcium; (3) combined stones having a cholesterol center and laminated exterior of cholesterol, bilirubin, and calcium; and (4) black or brown pigmented stones composed of calcium bilirubinate.

The first three types comprise the vast majority of gallstones and may be grouped together as cholesterol-based stones, pathogenetically related to abnormal cholesterol and bile salt metabolism. Black pigmented stones are commonly associated with chronic hemolysis, particularly sickle-cell disease. Gallstones stones occur in 40 to 60 percent of patients with sickle-cell disease. Brown pigmented stones are associated with infection. These were historically more common in China and Japan, perhaps related to bile stasis and infection caused by Ascaris lumbricoides (roundworm) and Clonorchis sinensis.

Etiology and Epidemiology

Though incompletely understood, the three major factors in gallstone formation are abnormality in bile composition, biliary stasis, and gallbladder infection. These factors are interrelated, but current thinking ascribes the primary role to abnormal bile composition, related to cholesterol and bile acid metabolism. This in turn is affected by dietary, genetic, and hormonal factors.

Famine can be defined as a failure of food production or distribution resulting in dramatically increased mortality. This increase is attributable to two, and very often three, orders of disease. First, there is the disease of general starvation characterized by wasting and inanition. Second, there are behavioral disorders and social disruptions, some a direct consequence of energy deficiency, others linked to mental disturbance. These can be lethal in their own right while at the same time contributing to the general starvation and to the spread of contagious illness. Third, there is epidemic infection, which is not always seen in mass starvation but which is frequent enough to be considered a classic concomitant. Facilitated by impaired individual and community resistance to pathogenic agents, contagions tend to run an exceedingly rapid course through famished populations, contributing in large measure to overall mortality.

General Starvation

Starvation, a condition in which the body draws on its own internal reserves for energy, arises from normal processes essential to survival. These processes lead to the disease of general starvation, or undernutrition, only after progressing beyond a threshold where damage resulting in functional incompetencies is done to active tissue. If starvation is not acute, that is, not rapidly induced, dysfunctions incompatible with heavy work are not apparent in nonobese people before the loss of 10 percent of prestarvation weight.

Ordinary starvation may be said to begin some 4 or 5 hours after a meal. It is then that the liver begins to release as glucose its store of glycogen. It is then that the liver begins to release as glucose its store of glycogen. As this process continues, muscle and adipose (fatty) tissue, which otherwise rely on free glucose for fuel, gradually revert to the oxidation of fatty acids.