Down syndrome, previously called “mongolism,” is a relatively common condition resulting from the presence of an extra chromosome, number 21, in all the cells of the body. In each human cell, there are 23 chromosome pairs containing basic genetic material that organizes the body’s development and physiological functioning. Each pair has a distinctive size and conformation and can be readily identified on microscopic examination. Chromosome pair number 21 is one of the smaller chromosomes. In Down syndrome there are usually three (trisomy) rather than two number 21 chromosomes (trisomy 21: found in 95 to 98 percent of all cases). In a small number of children with Down syndrome, the extra number 21 chromosome is attached to a chromosome of a larger pair (numbers 13 to 15; translocation Down syndrome–about 2 percent of all cases). In some children with the features of Down syndrome, the extra chromosome is present in less than 90 percent of the cells (mosaic Down syndrome–about 2 to 4 percent of all cases). Down syndrome is the most frequently occurring chromosome abnormality in live-born humans, and is also among the most frequently identified chromosomal abnormalities, representing about 4 percent of all aborted fetuses (Lilienfeld 1969). Down syndrome is usually recognizable at birth as a cluster of physical and neurological abnormalities (see Clinical Manifestations), which develop in a characteristic fashion during the life cycle.

The term tobaccosis in this essay denotes, collectively, all diseases resulting from the smoking, chewing, and snuffing of tobacco and from the breathing of tobacco smoke. They include cancers of the mouth, nasopharynx, larynx, trachea, bronchi, lungs, esophagus, stomach, liver, pancreas, kidney, bladder, prostate, and cervix, as well as leukemia. They also include atherosclerosis of the cardiovascular system – coronary heart disease (with ischemia and infarction), cardiomyopathy, aortic and other aneurysms, cerebrovascular hemorrhages and blockages; renal failure and peripheral vascular disease; emphysema and chronic obstructive pulmonary diseases; peptic ulcer disease and regional ileitis; cirrhosis of the liver; immunological deficiencies and failures of endocrine and metabolic functions; and fetal diseases and perinatal disabilities.

Tobaccosis is the foremost plague of the twentieth century and thus joins the most fearsome plagues that devastated humanity during this millennium such as the Black Death, smallpox, malaria, yellow fever, Asiatic cholera, and tuberculosis. But unlike microparasitic plagues, whose victims experienced pathognomonic disease manifestations within days or weeks of exposure, tobaccosis is an extraordinarily insidious disease entity of long latency resulting from exposure to tobacco for many years or decades and manifested by increased occurrence of any of a broad spectrum of neoplastic and degenerative diseases ordinarily associated with advanced age. Thus, the powerfully malignant nature and magnitude of the tobaccosis pandemic went largely undetected during the first four centuries of its global march; and it is only late in the fifth century of the post-Columbian world’s exposure to tobacco that the extent of tobacco’s depredations is being fully revealed.

Gangrene is the term used by the clinician to describe local death of tissue (necrosis) occurring in the living body. Gangrene implies a fairly rapid process (developing in days) extending over a large visible area (a few to many centimeters) with an obvious inability of the tissues to repair or replace the gangrenous part. Although gangrene can occur in internal organs (e.g., large intestine), it generally refers to a process occurring on the surface of the body. It may involve only the skin, or it may extend into deeper tissues such as muscle or nerves.

Gangrene may be either dry or moist. Dry gangrene describes necrosis of the tissues of the extremities resulting from vascular occlusion, such as occurs in severe arteriosclerosis of the legs. Wet or moist gangrene occurs when bacteria invades dead tissue, producing putrefaction. When the gas-forming group of bacteria is involved, gas gangrene occurs. A gangrene may be dry at first, and be converted to the moist type by invading bacteria.

Clinical Manifestations

In dry gangrene, the arterial supply is gradually cut off and a drying or mummification of the tissues results. There is frequently an absence of inflammation, but pain of varying degree may precede the color changes. The soft tissue slowly and progressively shrinks and the color gradually deepens until the whole area is coal black. Constitutional symptoms may occur but are less severe than in moist gangrene.

The giant intestinal roundworm, Ascaris lumbricoides, is a very common parasite with a worldwide distribution. The adult worms are 15 to 35 cm (6 to 14 inches) long and reside in the lumen of the small intestine. Sometimes, however, they are passed in the feces and, if vomited into the oral cavity, may exit from the host’s mouth or nostrils; thus they have been known to medical observers for millennia. Female worms produce up to 200,000 fertilized eggs daily, which are passed in the feces. Eggs incubate in the soil for at least 2 to 3 weeks to produce an infective larval stage within them. The eggs are very resistant to chemicals, desiccation, and extreme temperatures, but they mature or “embryonate” most rapidly in warm, moist, shady conditions in clay soils. People become infected by eating embryonated eggs in food or water contaminated with feces; or, in the case of toddlers, infection occurs by direct ingestion of eggs with dirt. Poor rural sanitation and the use of human feces for fertilizer obviously favor transmission. Mature eggs hatch in the small intestine, and the larvae then undergo a remarkable series of migrations in the host. They penetrate the intestinal wall and are carried in blood or lymph vessels to the liver and heart, and then the lungs. Here they break out into the air sacs, develop, and molt for about 3 weeks, and then climb up the trachea to the throat, where they are subsequently swallowed to establish themselves as adults in the small intestine.

Tay-Sachs disease (TSD) is the best known of the sphingolipidoses, a group of genetic disorders that includes Niemann-Pick disease, Gaucher’s disease, and others. Specifically, TSD is GM2 (beta) gangliosidosis, an autosomal recessive disease with complete penetrance. Affected individuals (recessive homozygotes) produce virtually no functional hexosaminidase A (hex A), an enzyme necessary for normal neurological development and function. TSD is very rare in most populations, but is, overall, about 100 times more prevalent among Ashkenazi Jews. This indicates that the TSD gene frequency is about 10 times higher in the Ashkenazi Jewish population. Persons with the disease usually show clinical symptoms of neurological degeneration by 6 months of age. Their condition steadily deteriorates, and they seldom live beyond the age of 4 years. There is no cure, but heterozygous “carriers” of the defective gene can be identified by clinical test, and amniocentesis can detect an affected fetus.

History

The British ophthalmologist Warren Tay (1881) first reported some of the early clinical signs of TSD. In the United States, Bernard Sachs (1887) further documented the clinical course and pathology of the disease he later called “amaurotic family idiocy” (Sachs 1896). 1896). It was Sachs who first noted the familial nature of the disease, and its seemingly exclusive occurrence in Jewish families. However, reports were soon made of non-Jewish cases. D. Slome (1933) was the first to survey the literature on the population characteristics of TSD and confirmed the disease’s autosomal recessive mode of transmission as well as the TSD gene’s higher frequency among Jews.

Schistosomiasis (bilharzia), known also by many local names such as “red-water fever,” “snail fever,” “big-belly,”and “Katayama disease,”is an “mmunologic disease”induced by eggs of blood-vesselinhabiting worms of the class Trematoda, genus Schistosoma. These eggs induce an immunologic response after they become trapped in the body organs, especially the liver, gut wall, and urogenital tract.

There are three major human schistosome species: Schistosoma haematobium, which inhabit the veins of the bladder area and whose eggs are discharged in the urine; and Schistosoma mansoni and Schistosoma japonicum, which inhabit the mesenteric veins supplying the intestines and whose eggs are discharged in the feces. In every case, however, the worms may also be found in the liver and portal system. There are also a few other species that can parasitize humans. These include the japonicum-like Schistosoma mekongi from the lower Mekong River basin, and some African schistosomes, such as Schistosoma intercalatum, that normally parasitize cattle and wild animals.

Terminology

The terminology of this disease is very confusing. Theodor Bilharz, the discoverer of the trematode worm responsible for the disease, placed it in the genus Distoma, a broad genus that was soon abandoned as more trematode species were discovered. Numerous generic names were thereafter invented to label the worm, including Schistosoma in 1858 (the name that must stand according to the rules of zoological nomenclature), Gynaecophorus in 1858 Bilharzia in 1859, and Thecosoma in 1860. Before World War II, however, in an understandable desire to honor the name of Bilharz, the disease was commonly called bilharziasis.

Old Diseases

It is very difficult to trace precisely the historical development of particular epidemic diseases in China. First, traditional Chinese medical terminology is based on a system hardly translatable into modern Western terms. Second, not only the concepts of disease, but the diseases themselves have changed, so much so that it is impossible to determine whether an ancient classical term meant the same thing when used in premodern texts, or to find the exact modern counterpart of a disease discussed in old texts.

Only during the second half of the nineteenth century did diseases in China begin to be scrutinized by Western medical practitioners, and as late as the early twentieth century, it was difficult to construct a complete picture because “there were classes of disease that were rarely brought for treatment to modern doctors” (Polunin 1976).

One principal feature of the traditional Chinese medical system (a system that achieved classical form by the second century) that makes it difficult to identify individual epidemic diseases in premodern China is the ancient categorization of both epidemic and endemic diseases along with other afflictions into a large group labeled shanghan (“affection by cold,” although today it is the modern term for typhoid fever). Ge Hong, one of China’s most important early medical thinkers, specified in the early fourth century A.D. that the Shanghan diseases included not only those caused by winter cold but also those caused by spring warmth and by seasonal liqi (epidemic “breath”). However, he conceded that differences among the origins of the three types of diseases were slight and they should therefore be grouped into a single category.

In recent years, occupational diseases have become an area of intense interest to medicine, public health, industry, and labor. Whole new areas of medical and public health specialization have developed since the end of World War II, partly in response to the detection of carcinogens in the workplace, dust in the air that workers breathe, and human-made chemicals that workers touch, taste, or inhale. Black lung (coal workers’ pneumoconiosis), brown lung (byssinosis), and white lung (asbestosis) are three industry-specific diseases that have gained international attention and highlighted the role of occupation in the creation of illness. Laborers as well as physicians have become acutely aware of the dangers posed by substances and materials at work in a host of industries from steel to petrochemicals.

The growing attention to the hazards of the industrial workplace has alerted workers even in “clean” worksites to occupational disease. Physical dangers are posed to office workers by video display terminals, poorly designed furniture, noise, and vibrations. Stress at the workplace is now seen as important in the creation of the modern epidemics of high blood pressure, heart disease, and stroke. The very definition of disease has been altered by a rising popular and professional consciousness of the importance of occupation as a source of illness.

The subject of early (for our purposes, pre–World War II) data on mortality is a vast one, and thus this treatment is quite broad. The emphasis is on identifying classes of data, sources of ambiguity, and general approaches to problems of interpretation. Wherever possible, citations are made to critical surveys of the literature, rather than to the literature itself. Some of the points discussed here can be extended, with appropriate caution and revision, to the equally important, but much less tractable area of early morbidity data.

Protostatistical Populations

There are rich opportunities for studying death and disease in populations for which vital statistics in the modern sense are nonexistent. Primary data sources include faunal evidence obtained by archaeological excavation, epigraphic evidence from funerary monuments, and information contained in parish records and family genealogies. In most cases, however, although these data allow inferences to be made regarding overall mortality among specific and highly localized populations, they contain little information on national-level populations and, with the exception of some faunal evidence, on causes of death. We can address the first shortcoming merely by assuming that the population studied accurately represents the total population, an assumption that is probably robust in very high mortality populations. The second difficulty – the lack of information on causes of death – is irremediable in the main. Furthermore, these data are rarely complemented by accurate population statistics, which are essential for computing rates and probabilities. Because of the dearth of early census data, genealogies and parish records, which provide a link between birth and death records, are especially important for estimating life expectancy (e.g., Henry 1956; Hollingsworth 1964; Wrigley 1968).

The pinworm Enterobius vermicularis (formerly Oxyuris) is a common parasite around the world and is the most prevalent parasitic helminth in developed countries today. Enterobiasis has afflicted and annoyed humans from ancient times; it was known to ancient Chinese, classical, and Islamic writers and was present in pre-Columbian America. Humans are the only hosts. Mature worms, ranging from 2 to 13 millimeters in length, inhabit the cecum and adjacent regions of the large and small intestines. Gravid females migrate out the host’s anus and deposit thousands of eggs on the skin of the perianal region. The eggs mature quickly and are infectious in several hours. Infection by ingestion of eggs from the hands is common, as the worms induce itching and scratching. Eggs are frequently eaten with contaminated food, and, because they are light, they are easily inhaled in household dust. Eggs hatch in the small intestine and develop into mature adults in as short a time as 4 weeks. Retroinfection, when the eggs hatch on the perianal skin and the larvae crawl back into the rectum, is possible but rare. Pinworms are especially prevalent among small children and often become a family affair.

Enterobiasis is rarely a serious disease. Intestinal disturbances, if any, are minor, but pinworms can cause great discomfort, and scratching can lead to secondary infections. Migrating worms occasionally reach the vagina or appendix, but rarely cause serious harm. Rectal itching and consequently insomnia, especially in children, are suggestive of pinworm infection.

The rickettsial diseases are a group of related maladies with common characteristics such as arthropod vectors, obligate intracellular etiologic agents, and similar symptoms, including skin rashes, high fever, and headache. The prototype is classic, epidemic, louse-borne typhus fever. Most other rickettsial diseases were originally described as “typhus-like” and were differentiated from the classic disease during the twentieth century.

Those whose etiologic agents share the Rickettsia genus with the historic disease are murine, or fleaborne typhus, Rocky Mountain spotted fever and other members of the spotted fever group of diseases, and scrub typhus or tsutsugamushi. Two other diseases, Q fever and trench fever, are also known as rickettsial diseases. In recent decades, however, key differences in the clinical manifestations, in mode of transmission, and in the physiology of the etiologic agents of these two diseases have caused them to be placed in separate genera.

Pathological rickettsiae were discovered early in the twentieth century and named after Howard Taylor Ricketts, a University of Chicago investigator, who lost his life in research on typhus in Mexico after several years of fruitful research on Rocky Mountain spotted fever. Although smaller than most bacteria, rickettsiae are visible under the light microscope. Unlike common bacteria, they are obligate intracellular parasites – that is, they metabolize and multiply only inside living cells, a characteristic shared with the viruses. This peculiar combination of traits caused the rickettsiae to be classified for several decades as organisms midway between bacteria and viruses. By the late 1960s, however, research revealed that they were true, if highly fastidious, bacteria.

It is often thought that analytic philosophy arises, at least in part, from a reaction against Hegel, or against philosophy inspired by Hegel. To some extent this is correct. The philosophy of Bertrand Russell and G.E. Moore in the first decade or so of this century, which was enormously influential for subsequent analytic philosophy, was developed in conscious reaction to idealist views that owed much to Hegel. This fact, however, does not settle the question of the influence of Hegel, either on Russell and Moore or on analytic philosophy more generally; all that it does is to give us a way of posing the question. And the question is a complex one. Besides the general difficulties involved in tracing the influence of a view as complex as Hegel's, there is also a particular problem arising from the relation between Kant and Hegel.

Favism is an acute hemolytic reaction triggered by exposure either to fava beans (Vicia faba) or to certain drugs (e.g., sulfa-based antibiotics and the antimalarial primaquine) in people with an inherited deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD). In favism, the patient can suffer from destruction of red blood cells, severe anemia, and possibly death. There are two necessary conditions for the disease: (1) genetic inheritance of the “Mediterranean” variant of the abnormal gene trait for G6PD deficiency; and (2) ingestion of fava beans, usually fresh, or exposure to some drugs. The bean is a dietary staple in areas where favism is reported. Only an estimated 20 percent of those with the genetic trait for G6PD are likely to experience episodes of favism. Under modern medical conditions the hemolytic anemia caused by favism is only rarely fatal. Strong evidence suggests that both the gene for G6PD deficiency and the cultural practice of fava bean consumption are evolutionarily adaptive traits that protect against death from all types of malaria. Favism, then, could be described as a negative outcome of the interaction of the positive adaptive qualities of both the gene and the bean.

Distribution and Incidence

Favism is found primarily in the Mediterranean and Middle East regions where fava beans are a staple food and the Mediterranean variant of G6PD deficiency gene is relatively common. Mark Belsey (1973) reports that it is frequently encountered in Greece, Sardinia, Italy, Cyprus, Egypt, Lebanon, Israel, Iran, Iraq, Algeria, and Bulgaria, and is particularly common among Sephardic Jews.

Tetany is a symptom complex characterized by painful and prolonged contractions of the (generally smooth) muscles. These often appear as convulsions and are usually triggered by hypocalcemia. Adult varieties of the condition that result from calcium or magnesium deficiencies include maternal tetany, parathyroid tetany, osteomalacic tetany, and magnesium tetany. Alkalosis can also produce tetany. Examples include gastric tetany and hyperventilation tetany, following a lengthy period of forced inspiration and expiration. Another form of the disease – grass tetany caused by magnesium deficiency – is found in cattle. Despite these many forms, however, the disease occurs chiefly in infants (neonatal tetany) and young children (infantile tetany) in whom it is normally associated with rickets. It affects males far more than females and, in the absence of proper treatment, frequently proves deadly.

Distribution and Incidence

Because tetany has so often been confused with tetanus, very few data are available on the geographic distribution of the disease. It probably occurs worldwide in the temperate zones, with the highest frequency of neonatal tetany among bottle-fed, black, and prematurely born infants. An abundance of year-round sunshine and, hence, vitamin D may have the effect of reducing the incidence of infantile tetany in the tropics. The incidence of neonatal tetany recorded at New York Hospital between 1940 and 1958 was between 1 per 500 and 1 per 700 births.

The “Black Death” is the name given by modern historians to the great pandemic of plague that ravaged parts of Asia, the Middle East, North Africa, and Europe in the middle of the fourteenth century. Contemporaries knew it by many names, including the “Great Pestilence,” the “Great Mortality,” and the “Universal Plague.” This epidemic was the first and most devastating of the second known cycle of widespread human plague, which recurred in waves, sometimes of great severity, through the eighteenth century. Some of the later and milder “plagues” in this period seem to have also involved other diseases, including influenza, smallpox, and dysentery. Nonetheless almost all historians agree, on the basis of contemporary descriptions of its symptoms, that the Black Death should be identified as a massive epidemic of plague, a disease of rodents, caused by the bacillus Yersinia pestis, that can in the case of massive epizootics be transmitted to human beings by fleas. Although the Black Death manifested itself most commonly as bubonic plague, it also appeared at various times and places in its primary pneumonic and septicemic forms.

History and Geography

The geographic origins and full extent of the Black Death are still unclear. The earliest indisputable evidence locates it in 1346 in the cities of the Kipchak Khanate of the Golden Horde, north and west of the Caspian Sea. Until recently, most historians have claimed, based on Arabic sources, that the epidemic originated somewhere to the east of the Caspian, in eastern Mongolia or Yunnan or Tibet, where plague is enzootic in various populations of wild rodents.

Scurvy is a deficiency disease, arising from a lack of vitamin C (ascorbic acid) in the diet. It occurs most characteristically in the absence of fresh fruit and vegetables, but can still be avoided when these are not consumed if the diet is rich in uncooked meat as in the case of Eskimos (heat destroys the vitamin). Scurvy does not appear in a regularly recognizable way in the ancient medical literature, and its name is not classical but, rather, derived from the north European vernaculars of the Renaissance. It was, for example, schverbaujck in Dutch and scorbuck in Danish, and Latinized in 1541 by Johannes Echthius, a Dutch physician living in Cologne, as scorbutus. In the slave trade it was often called the mal de Luanda.

Etiology, Epidemiology, and Distribution

Human beings, like guinea pigs and monkeys but unlike many other animals, do not synthesize vitamin C. No doubt this reflects a period of evolution in a vitamin C–rich environment; and, with the expansion of the species to all parts of the Earth, less generous climates have inevitably taken a toll due to scurvy. The disease occurs where economic, social, or climatic factors prevent access to an appropriate diet, and frequently has appeared under circumstances where diets are circumscribed, including long sea voyages, during military operations, in prisons, with the failure of crops, and during the Gold Rush. In the modern period, infantile scurvy has been a problem, for example, in Canada during the decades 1945–65, where it occurred mostly among the lower socioeconomic groups.

The larval stages of three tapeworms of the genus Echinococcus can cause severe disease in humans. All three normally become adults in the intestines of dogs or other canids. Eggs are passed in the feces and, if ingested by a herbivore, develop in the liver or other organs into a saclike container of larvae, the hydatid cyst. Carnivores become infected by eating cysts with the flesh of the herbivore. Echinococcus granulosus, which commonly has a sheep–dog cycle, but which may also infect goats, cattle, swine, and camels, is the most likely to infect human beings. Human echinococcosis occurs primarily in sheeprearing areas. Dogs ingest cysts in the offal of dead sheep and pass eggs in their feces. Humans acquire the eggs from a dog’s fur or from contaminated food or water. Cysts holding 2 or more liters of fluid and larvae can grow for years in the liver, lungs, brain, or other organs and exert enough mechanical pressure to cause grave or fatal consequences. Rupture of a cyst by trauma or surgery releases daughter cysts, which may grow elsewhere in the victim; the hydatid fluid can cause fatal anaphylactic shock. Hydatid cysts in humans and animals have been known since Roman times, but, as was true for the other tapeworms, the relationship between the larval cyst and the adult worm was not suspected until the eighteenth century. E. granulosus was described as a separate species in 1850, and its life cycle was worked out with feeding experiments in 1863.

Amebiasis is an infection of the colon caused by a parasitic protozoan, the ameba Entamoeba histolytica. Several species of ameba inhabit the large intestine. Most are harmless commensals or minor parasites, usually causing little or no clinical damage. The closely related species Entamoeba coli and Entamoeba hartmanni are commensals, and infection with E. histolytica is also often asymptomatic. E. histolytica is probably a species complex, with a number of morphologically similar forms with varying degrees of invasiveness. E. hartmanni, formerly believed to be a “small race” of E. histolytica, is now recognized as a separate nonpathogenic species. Pathogenic amebas cause light to severe intestinal damage (amebic dysentery) and sometimes spread to the liver, lungs, brain, and other organs.

Etiology

The parasite exists in two forms during its life cycle. Active adults, trophozoites, multiply in the lumen of the colon. They frequently live there harmlessly, feeding on the contents of the intestine. Some strains are generally commensal; others are highly pathogenic. Under conditions of stress, lowered host resistance, or when a particularly pathogenic strain is involved, amebas invade the intestinal wall and cause abscesses. As they pass lower into the large intestine, the drier environment stimulates them to form a cyst wall. The original cell nucleus divides twice, producing four daughter nuclei. nuclei. Cysts are passed with the feces and are infective when swallowed. Excystation takes place in the small intestine, and the young trophozoites, four from each cyst, are carried in the fecal stream to the large intestine. When dysentery occurs, trophozoites are swept out too rapidly to encyst. Even though huge numbers of amebas may be passed, they die quickly and are not infective.

Pica is usually described as a pathological craving for nonfoods, although it can mean a craving for substances generally accepted to be food as well. Medical science has long been interested in this disorder, for although it does not constitute a disease, it is often a symptom of disease and frequently is associated with nutritional deficiencies, especially those connected with minerals. In addition, psychiatry and psychology find that pica is often connected with mental problems, including those of retardation. Anthropologists study it as a cultural phenomenon, since it has been associated with some religions and also perhaps because the use of nonfoods is indicative of food shortages in the distant past.

The word “pica” comes from the Latin for “magpie,” a bird that eats practically anything. The term was first used by Ambroisé Pare in the 1500s, although references to pica consumption can be found in many ancient and medieval writings. M. H. Boezo, in his 1638 work De Pica, was the first to draw a distinction between “pica,” which he believed was an appetite for “absurd things,” and which was common in both men and women, and “malacia,” which referred to a voracious desire for normal food substances. He observed that the latter occurred most often in pregnant women, and believed the cause was a mental alteration caused by the pregnancy.