The description and pharmacologic modification of disease are of paramount interest to everyone in­volved—clinical practitioners, scientists, and patients alike. We must not, however, allow the fight against disease to lead to abuse of human volunteers or to the development of potentially harmful remedies produced for large-scale consumption. Protecting human volunteers is, or should be, the concern of all researchers. Volunteers deserve a thorough explanation of the risks and possible consequences of research. To ensure that subjects receive proper treatment, most research centers have a "human-subject review committee" composed of physicians and lay individuals who judge prospective research projects to determine whether the projects are safe for humans and whether they are appropriate for human participation. These com­mittees make sure that research is explained to volunteers —both verbally and in writing—and that both written and verbal consent are obtained before a person participates in a scientific study. Most review committees assess projects on a continuing basis. In general, universities and research institutions do not sanction research in humans that does not meet the standards of the committee involved. Similarly, reputable scientific journals have policies of not publishing the results of experimentation in humans unless the research has been reviewed and approved. One aspect of the research review process is that of new drugs. Although new drugs offer the possibility of solving old problems, they also pose serious threats if not adequately evaluated ahead of time. The U.S. Food and Drug Administration (FDA) is charged with investigating and licensing drugs in the United States, which involves the strict regulation of tests of new products and clinical investigators. Usually, the investigators are physicians who wish to use volunteers in clinical trials of new drugs not yet approved. To be approved, a new drug must undergo several phases of in­vestigation. The first phase is that of experiments in animals. In this phase, laboratory animals are studied so that obvious toxicity can be ruled out. If a drug passes this stage successfully, it is cleared for the first phase of human research and is administered to a small number of normal human volunteers. This part of the testing is designed to ascertain a drug’s safety before its use for specific diseases. From this phase the drug moves to phase 2 of the investi­gation, where it is studied in a few human subjects with health problems which, it is believed, the drug under investigation will relieve. The drug is tested for safety and effectiveness af specific dosage levels. Information about the best dosage and frequency of administration is often determined in this phase of research. The next phase, phase 3, involves testing on a greater scale, to gain information about the effectiveness and possible side effects of the drug under study. The final phase, phase 4, is conducted after the drug has been marketed, and involves large-scale, long-term testing of the drug. It is easy to understand why many years may pass before all phases of the testing of a new drug have been completed to everyone’s satisfaction, both the FDA’s and the manufacturer’s. This period is often frustrating for patients and physicians, but it is essential if mistakes with potentially dangerous consequences, are to be avoided.

When allergic people travel or move to other regions of the country, their symptoms may change, and most often these variations are caused by regional differences in pollen-producing plants. Other factors, however, including airborne fungus spores, algae, and insect fragments, as well as food components, also can vary from place to place and affect a patient’s health accordingly. At times, desired symptom improvements do not occur despite carefully planned major geographic moves. In effect, allergens from domestic dust, bedding, upholstery, and house pets accompany the patient and continue to provoke illness in the new surroundings. These factors, reflecting household practices and life style, have indoor or job-related sources and can be effectively eliminated by applying practical environmental measures. Allergic symptoms also may recur in distant places because of acquired sensitivity to allergens (for example, pollens) unique to the new area. More often, the disappointed patient has simply not yet left the range of an offender allergen despite a journey of hun­dreds or even sometimes thousands of miles. As many grasses and tree species, for example, grow throughout the continent, avoidance of their pollens is difficult and requires careful selection of refuge areas. Thus, permanent geographic moves to change allergen ex­posure should not be undertaken impulsively. They might be con­sidered after successful trial periods in the area under consideration. While allergic problems may be difficult to predict in a new area, some estimate of expected allergen exposure is possible. The follow­ing charts should assist such speculation as well as indicate the al­lergens that may produce recurrent symptoms in established regional populations. To simplify reference, groups of states and bordering Canadian provinces with similar climate and pollen allergens are considered together. As the resulting groupings are large and not strictly uniform,
these charts only describe average conditions. Points close to a boundary between two areas will, of course, have allergens typical of both. For each region, important hay fever plants are listed with the time of pollen shedding for each indicated with respect to the calendar year, with the horizontal bars across the columns indicating the time of the allergen occurrence. Plants that are mostly cultivated are marked (C), and sources restricted to part of a region are de­noted by (N) North, (S) South, (E) East, (W) West, (L) Local, and (NW) Northwest. In each table, noteworthy pollen-producing trees are noted first, followed by grasses, and broad-leafed plants without woody stems (or weeds). For each type, an approximate indication of the im­portance of an allergy offender in the overall region is given on a scale ranging from ± (minor) to -| —1—|- (very major). The reader should understand that these appraisals are overall averages for entire regions and their allergic populations. Differ­ences in individual sensitivities and the local distribution of sources (such as pollen-producing plants) may convert a generally unim­portant pollen type into a major cause of symptoms. Other factors —Pine, spruce, fir, and hemlock pollens are released in large amounts but are not proven factors in hay fever and asthma. Some ragweed occurs where the forest has been disturbed. Fungi— especially mushrooms and puffballs—are abundant (June-October) but seem to cause only limited symptoms. Cabins and cottages that have been left closed for many months and that are often not fully watertight tend to be moldy. Tables on pages 140-153 adapted from material originally appearing in A Manual of Clinical Allergy, J. M. Sheldon, R. G. Lovell, and K. P. Mathews, editors and reprinted by permission of W. B. Saunders, Philadelphia, PA. Copyright © 1953. Other factors —Insect scales and hairs may provoke symptoms in such localities as inland lakes where certain types swarm seasonally. Fungi are important factors from May to November, especially in grain-growing areas; exposure increases whenever vegetation or soil is disturbed. Plants that process seed materials—such as castor bean, cottonseed, and soybean—may release dusts that cause allergic reactions. Other factors —Fungus exposures can produce symptoms during much of the year. High humidity encourages fungus growth and may directly affect respiratory symptoms.







Other factors —Pollens from eucalyptus, Brazilian pepper tree, palms, and other cultivated trees occur but are probably minor factors at most. Fungus spores in moderate numbers are airborne throughout the year, and indoor fungus growth is fostered by the continuously high relative humidity.

Other factors —Extensive livestock operations provide local sources of animal dander exposure. In addition, dusts from fertilizers and animal feeds, as well as from grain-storage facilities, can create serious allergic problems. Cultivated areas are especially important sources of fungus spores from early summer to the first snowfall. Other factors —In this region, huge amounts of pollen are released by conifers—including pines, spruce, fir, and hemlocks—but their effect on allergic people remains in dispute. Fungus spores derived from field crops are less abundant than in areas located farther east. Other factors —In hilly areas, birch, aspen, and oak pollens may cause seasonal allergy. Fungus exposures are only rarely a source of major symptoms.






Other factors— Pollen produced by tamarisks and mesquite or by plantings of castor bean, pecan, or eucalyptus may, in rare instances, produce respiratory allergy. Fungus exposures are relatively low, although extensive irrigation promotes fungus growth. The use of evaporative ("swamp") cooling units in buildings increases indoor fungus exposure, although the risks involved are not precisely known. Other factors —The effects produced by eucalyptus, coast maple, 1 and acacia pollens are unknown. Fungus exposures vary from mild to moderate according to the density of local plant cover. Other fa
ctors —Areas devoted to grass-seed production may ex­perience high grass-pollen levels as a result. Large amounts of conifer pollen are shed, especially at higher elevations, but they are generally of uncertain importance in allergy. Respiratory illnesses, including asthma, are associated with wood industries, most notably where western red cedar is processed. Fungi flourish in humid coastal areas; the types present, however, seem to cause milder symptoms than does exposure in grain-growing areas of eastern regions.

Allergic skin disease is another research challenge. Atopic derma­titis, or eczema, is an itchy rash which typically starts in early childhood. It is usually, but not always, found in people with other allergic manifestations, such as asthma or rhinitis. Sometimes the disease can be treated successfully by removing or avoiding antigens in the environment, but it is frequently chronic. Although researchers characterize allergic skin disease as an itchy, scaly red eruption, they know little else about its causes. The extent of their knowledge is that many individuals afflicted by it have defects in cellular immunity, for example, abnormal T cell numbers or abnormal white blood cell mobility toward known chemical attractants (chemotaxis), or both. What interests many scientists are the natural history of atopic dermatitis and whether the imposition of environmental controls early in a patient’s life can alter that history. The use of topical corticosteroids (to decrease inflammation), skin softeners, and anti­histamines (to decrease itching) are all being studied. Many individuals, both allergic and nonallergic, suffer from urticaria, commonly known as hives. Urticaria is an itchy skin eruption characterized by wheals, or small welts, on a flared, red base. Angioedema is a disease characterized by, among other things, swelling of the deep skin layers. Researchers now know that hives occur when mast cells in the skin release the mediator histamine. Histamine causes dilatation of blood vessels, leakage of fluid into the skin layers, and itching. The result is engorgement, wheal formation, redness, and itching. Research has confirmed that many different stimuli may contribute to the production of hives. Such immunological reactions as those that provoke allergic asthma and rhinitis can become concentrated in the skin, appearing as urticaria; but nonimmunological factors can also trigger the release of histamine by mast cells. Cold; heat; sunlight; systemic disease (for example, rheumatic disease and thyroid disease); certain viral infections; inherited conditions; and possibly psychological factors —all are physical conditions or factors that can provoke hives at certain times in susceptible individuals. Although histamine has been determined to be the main mediator responsible for hives, other, so-far-undefined mediators probably remain to be discovered. Researchers do not, for example, know how such a variety of nonimmunologic events as physical stimuli, infection, and psychology affect mast cells. What, besides nonimmune events, happens to make mast cells produce histamine, and why are some people and not others stimulated by specific stimuli to develop hives?

(not egg-free)

In an 8-inch square pan, thoroughly mix together meat, onion, salt, potato, garlic powder, and egg, and form a loaf of about 7 inches X 1 1/2 inches. Firmly press mushroom slices over entire surface of loaf. Bake in 350° F oven for about 1 hour. Slice and serve with ketchup. Serves 3.

A substance used to thin secretions.

Allergic disorders are seldom fatal, though it is estimated that about five thousand people in the United States die each year from asthma. There are approximately forty deaths each year from allergic reactions to insect stings. Reactions from some drugs, and from cer­tain foods such as nuts and seafoods, have occasionally proved fatal. Asthmatic patients are at additional risk when undergoing surgery that involves anesthesia.

An allergist is a medical doctor certified by the American Board of Allergy and Immunology who specializes in the diagnosis and treatment of allergies.

There are many possible allergens. For example: pollen, mold, and house dust; animal dander (skin shed by dogs, cats, horses, rabbits, and so on) ; feathers (as in old-fashioned pillows); kapok, wool, dyes, and industrial chemicals; foods and medicines; and insect stings.