Archives consist of articles that originally appeared in Collier's Year Book (for events of 1997 and earlier) or as monthly updates in Encarta Yearbook (for events of 1998 and later). Because they were published shortly after events occurred, they reflect the information available at that time. Cross references refer to Archive articles of the same year.

1938: Medicine

In the field of Medicine and Surgery, progress continues to be made with rapid strides. Since some of the advances have been in especial technical domains, comments in this report will be limited to the more important achievements in the diagnosis and treatment of some of the commoner diseases in which the general public as well as physicians may be interested.

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The results of researches upon a great variety of infectious diseases due to micrococci (especially streptococci, staphylococci, pneumococci, gonococci, and meningococci), to bacilli of various sorts, to organisms like amœbae, malarial parasites, trypanosomes, spirilla and spirochetes, and to the so-called 'filtrable viruses' are reported in ever-increasing numbers in the medical journals. Space will permit of reference to only some of the more outstanding advances in knowledge that have recently been made.

Of the hemolytic streptococci (Types A, B, C, D, E, F, and G), the beta group (B) is the exciting cause of more infections than any other type, since the beta-hemolytic streptococcus is the variety found in surgical sepsis, in erysipelas, in puerperal fever, in streptococcic sore throat, in hemolytic streptococcus meningitis, and in hemolytic streptococcal septicemias. On the other hand, one of the worst forms of streptococcal infection (malignant ulcerative endocarditis) is due to the non-hemolytic Streptococcus viridans. Aside from comprehensive biological studies of the several types of streptococci, the most important recent advance in this domain lies in the discovery of certain extraordinarily efficacious drugs for combating acute infections due to streptococci — namely, the so-called 'sulphonamide compounds,' including prontosil, sulfanilamide, and pyridin sulfanilamide (M. & B. 693). Here an entirely new era of chemotherapy has been opened. Though very efficient in the treatment of acute infections, these drugs do not seem to cure chronic infections and will not sterilize 'streptococcus carriers.'

Sulfanilamide is administered by mouth in doses proportional to body weight. The use of the drug by intravenous, intramuscular, and intraspinal injection is now being cautiously experimented with. This drug should never be used indiscriminately, as some persons are hypersensitive to it.

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The treatment of hemolytic streptococcus meningitis by sulfanilamide has yielded revolutionary results; the mortality rate (formerly 95 per cent) has been reduced to less than 20 per cent.

In 1938, over 75 deaths followed the administration of a so-called 'elixir of sulfanilamide (Massengill).' The toxic ingredient in this was diethylene glycol, not the sulfanilamide.

In the prevention and treatment of scarlet fever, 'scarlet fever streptococcus antitoxin serum (Dick)' is believed to be valuable.

The Staphylococcus aureus and albus may be the cause of boils (furunculosis), carbuncles, other local abscesses, septicemia, or acute osteomyelitis. In addition to surgical intervention, intensive treatment with some of the newer sulfonamide compounds may be tried. In the German literature, the use of uliron (ZP 90) has been recommended especially for this purpose, but too often it causes a neuritis. In this country, sulfapyridin is sometimes effective in staphylococcus septicemia.

In patients subject to recurring staphylococcal infections of the skin (boils, carbuncles, acne, etc.) staphylococcus toxoid has been given subcutaneously or intramuscularly.

The treatment of pneumonias and of septicemias due to the pneumococcus (Diplococcus pneumoniae) is being rapidly improved. No less than 32 types of pneumococci can now be differentiated; and for successful treatment it has been desirable to determine, in any given pneumococcus infection, the particular type of pneumococcus that is the cause. Antipneumococci sera (from immunized horses and rabbits) for Type I and Type II and for several other types (V, VII, VIII, etc.) are now available and, if promptly used in adequate dosage, will greatly reduce the mortality from these infections.

Recently, nine different types of pneumonia (I, II, III, V, VI, VII, VIII, XIV, and XVIII) have been treated with unconcentrated homologous antipneumococcus rabbit serum. The results obtained with Type III were not such as to indicate effectiveness of the serum, since the mortality rate in thirteen patients treated was 46 per cent. In 54 cases due to eight other types of pneumococcus, treated with antipneumococcus serum of homologous type, the mortality rate was only 3.7 per cent.

During the past few years, attempts have been made in some localities to reduce the mortality rate of lobar pneumonia and bronchopneumonia (irrespective of types) with parenteral injections of deuteroproteose.

Very recently, attempts have been made to supplant serum treatment by administration of a new compound, namely sulfanilamide-pyridin (sulfapyridin M. & B. 693). Preliminary reports are very encouraging, even in the treatment of Type III pneumonias. If present expectations should be realized, the typing of pneumococcus strains and the administration of sera might become unnecessary. Much more experience with this new drug will, however, be required before safe conclusions concerning its efficacy dare be drawn. Fortunately, the drug firm that owns the patent rights for the product in this country has as yet withheld it from the market, placing quantities of it instead in the hands of competent medical investigators who will determine the proper dosage as well as the advantages and the limitations of the drug.

It is suggested by some that the sulfanilamide preparations owe a part of their efficacy (1) to injury to the capsules of cocci, making the germs susceptible to phagocytosis, and (2) to neutralization of some of the toxic products of the bacteria.

Pneumococcic meningitis (formerly always fatal) can now be cured in about 20 per cent of the cases by the combined use of sulfanilamide and specific sera (from horse or rabbit).

New methods for treating gonococcal inflammations of the urogenital organs, gonococcal endocarditis and septicemia, and gonorrheal rheumatism have been introduced and have yielded unexpectedly rapid and satisfactory results.

From 70 to 90 per cent of gonococcal infections are said to be cured when treated with large doses of sulfanilamide (in hospital beds under constant supervision); results in patients who are allowed to be up and about and given smaller doses of sulfanilamide are less satisfactory.

Fever therapy, when properly used, is one of the best methods for combating gonococcal infections (especially gonorrheal arthritis); but its application is limited by the costs of the apparatus and of hospital treatment and by the fact that it must not be used on patients with severe circulatory or renal disorders. Patients over 60 years of age should be excluded from fever therapy. An air-conditioned Kettering hypertherm (adapted for hospital use) seems to be the apparatus of choice. The patient is placed in the chamber heated to 130° F. with humidity of 75 per cent. The patient's temperature gradually rises (within one or one and a half hours) to 106° or 107° F., which seems to be optimal for the treatment, though some advise temperatures not exceeding 105° F. since occasional fatalities have been reported. Owing to the rapid loss of fluids and chlorides, the patient is given large quantities of iced 0.6-per cent salt solution. The number of treatments required varies with different individuals; four or five will suffice for the majority, though some may require ten or even fifteen treatments.

Heat applied by other methods (diathermy; incandescent electric-light baths; electropyrexia; vapor-Russian baths, etc.) is valuable, but less efficacious than the fever produced in the 'hypertherm.'

In meningitis due to the meningococcus, the early injection of anti-meningococcus serum, or of meningococcus antitoxin into the subarachnoid space while giving also some form of sulfanilamide, either by mouth or by subcutaneous injection, is at present the preferred form of treatment. Serum and prontosil together appear to be more effective than either alone. Recently, sulfapyridin by mouth has been reported as a successful chemotherapeutic agent in meningococcal meningitis.

The majority of epidemics of meningitis are due to meningococci of Types I and III. Types II and IV are more common in chronic meningococcus carriers.

This disease, due to infection with Brucella melitensis, is now prevalent in various parts of the United States. It was formerly treated mainly by injections of killed cultures of the causal microorganism (Brucella melitensis vaccine) but during this year favorable results have been reported from the use of sulfanilamide (or of one of its derivatives). Though rather large doses of the drug are required, the results obtained are equal (or perhaps superior) to those following any other form of therapy. Good results have also followed intravenous administration of neoarsphenamine, as well as physically-induced hyperpyrexia (fever treatment).

Attention has repeatedly been drawn to the frequency of involvement of the nervous system and of the meninges (meningo-neurobrucellosis) in chronic undulant fever in this country and abroad.

Diphtheria still occurs far too often, despite the fact that the disease is now definitely preventable, and modern immunizing agents are safe, simple, and efficient. The subcutaneous injection of 'diphtheria toxoid, alum precipitated (refined)' is at present the method of choice, preferably given in two doses to children, a small initial dose and a larger dose four weeks later. In immunizing against diphtheria, the physician may, if he desires, simultaneously immunize against tetanus by using 'diphtheria toxoid, tetanus toxoid, alum precipitated combined.' If there were general extension of active immunization to the whole child community, it is probable that diphtheria could, within one generation, be removed from the fatal diseases of childhood.

Modern control of water and milk supplies has done away with the devastating epidemics of typhoid with which the older physicians now living were so familiar in their early practice. The isolated cases and the small epidemics that still occur are due in the main to infection from typhoid-bacillus carriers. The most famous of these carriers was the woman known as 'Typhoid Mary,' a cook. It was observed that wherever she was employed cases of typhoid fever occurred. Her role as a bacillus, carrier was recognized in 1907 and she was kept in a detention hospital by the Health Department for three years. She was released in 1910 and disappeared for five years, during which she was the cause of at least ten outbreaks of typhoid fever and 57 cases. From 1915 until her death on Nov. 11, 1938, at the age of 70, she was detained in Riverside Hospital by the New York City Department of Health.

For early diagnosis, in addition to the history and general physical examination, examination by X-ray occupies a preeminent place. Laboratory studies are now more thorough than formerly; in addition to examinations of direct specimens of sputum, the concentration method is used, cultures are made, and guinea-pig inoculations are resorted to when ordinary specimens are negative.

The prevention of tuberculous infections, as well as their early detection, has made rapid progress since the public has become better educated regarding the tuberculosis problem, and since state and city health departments, school and college authorities, and individual practitioners have learned the importance of a search for the disease among apparently healthy persons. Some conflict has arisen between public health administrators and private medical practitioners, but the rights of individuals as well as the rights of society are gradually becoming better defined. Enthusiasm regarding immunization by oral vaccination with B.C.G. has subsided, though it is admitted that the method is harmless and is of some value, especially for children forced to live in tuberculous surroundings. Separation from tuberculous persons is still the best method of preventing the disease.

In the treatment of pulmonary tuberculosis, phrenic interruption, or collapse of the lung by artificial pneumothorax (unilateral or bilateral), along with other treatment, especially in early cases, prolongs by many years the expectation of life.

Attempts to discover an effective chemotherapy for tuberculosis have been hitherto futile. Recently, certain chemicals have been recommended for the treatment of extrapulmonary tuberculosis. Thus triphal has been used in lupus, but many patients exhibit intolerance to it. The latest suggestion is the use of rubrophen (a triphenylmethan derivative) for the treatment of tuberculosis of the bones, joints, lymph glands, eyes, or skin. The drug is given by mouth and also (cautiously) by intravenous injection. Reports of its efficacy when given patiently over longer periods (in association with other anti-tuberculous treatment) have been favorable, but clinicians must remain skeptical pending further trials of this medicament.

Emphasis is now laid also upon vitamin C. deficiency in patients suffering from pulmonary tuberculosis (deficiency easily determined by quantitative estimation in urine and blood). Removal of such deficiency by administration of the vitamin (cevitamic acid) is asserted to increase the resistance of the organism in tuberculous patients and to be a valuable adjuvant to other forms of therapy.

Despite efforts to control the disease, it still occurs sporadically and in small epidemics. The remedy of choice at present is carbarsone given over a period of ten days, and after a rest period of ten days a second course may be given. Repeated examinations of the stools should be made until the physician is sure that neither motile forms nor cysts of Endameba histolytica are any longer present.

Amebiasis should be made a reportable condition; and, where epidemics occur, surveys of the population by skilled health laboratory workers should be made in order that carriers may be detected. Food handlers should be especially suspected. Protection of food and drink from flies and other insects (cockroaches) should be arranged for.

Various members of a large series of varieties of Anopheles mosquitoes are now known to transmit malaria; the variety responsible in one region is often absent from other regions in which malaria is prevalent.

Though quinine in adequate dosage will cure most malarial infections, yet when gametocytes tend to persist in the blood, a plasmochin tablet should be given each night.

In all forms of malaria (and especially in 'cerebral malaria'), the acridin dye known as 'atabrine' has been found to be very efficacious as a curative agent, as it rapidly kills the asexual forms of the malarial parasite.

The magnitude of the problem of the prevention of malaria is well illustrated by the estimate that some 1,600,000 persons are at present infected with the parasites in seven Southern States (South Carolina, Georgia, Florida, Alabama, Tennessee, Mississippi, and Louisiana).

The treatment of this disease (due to infection with Treponema pallidum) with courses of arsphenamine and its derivatives (especially neoarsphenamine or mapharsen given intravenously), alternating with courses of intramuscular injections of insoluble compounds of bismuth has been revolutionary in contrast with the less satisfactory results formerly obtained by treatment with mercury and iodides alone. Recognized early and skillfully treated, syphilis is curable, and the formerly much dreaded parasyphilitic diseases of the nervous system (general paresis and locomotor ataxia) can be prevented from developing. A great recent advance has been the inauguration by the Surgeon General of the United States Public Health Service of an active campaign against syphilis, bringing the disease out into the open, educating the public regarding methods of prevention and cure, and securing large Federal and local grants for use in suppressing the scourge.

At the time of writing, great progress is being made in our knowledge of the relatively-large group of diseases due to infection with ultramicroscopic viruses, or so-called 'filtrable viruses' — agents that are so small that they will pass through filters that will hold back all forms of bacteria.

Proven virus infections include human rabies, poliomyelitis (infantile paralysis), influenza, the common cold (See below under DISEASES OF THE RESPIRATORY SYSTEM), certain types of encephalitis and lymphocytic choriomeningitis. It seems probable that yellow fever, epidemic encephalitis, whooping-cough and measles also are virus diseases. In 1938 it has been asserted in Germany that viruses have been demonstrated to be the cause of German measles (rubella), epidemic parotitis (mumps), and aphthous stomatitis (canker), the work having been greatly facilitated by fluorescent microscopy, a late improvement in this field.

The sulfanilamide compounds, so useful in the treatment of certain bacterial infections have thus far not been shown to be effective in human virus infections, though in 1938 it was reported that they would cure 'distemper,' a virus disease of dogs and cats.

The virus can now be grown in tissue cultures. Remarkable similarities of rabies virus to pemphigus virus have been described. The relative value of dried cord vaccines and of phenol vaccines against rabies is now under study. In Trinidad certain bats and in South Africa the genet and the mongoose have been found to be carriers of rabies virus.

Studies of the virus of pseudo-rabies of Aujesky (not transmitted by bites) indicate that it is a unique form of virus that is very difficult to immunize against. Infected animals are especially prone to die during the night.

(Infantile Paralysis; Heine-Medin Disease). Three important advances in connection with this disease may be chronicled: — (1) studies of the mode of infection and attempts at prevention; (2) the use of the so-called 'iron lung' for patients whose respiratory muscles have been paralyzed; and (3) accumulation of funds for study and treatment by a National Foundation.

Some evidence has been gathered in favor of the view that in epidemics of acute poliomyelitis the portal of entry is the nose, the virus traveling along the olfactory nerves into the cerebral nervous system. Based upon this view, children at times of epidemic occurrences are now being subjected to chemoprophylactic treatment. The child lies upon a slanting table, over the end of which its head hangs in an inverted position while instillations of zinc sulphate solution are made into the nostrils (slowly along inner surface of dorsum of nose). More experience is necessary to determine the value of the method.

It is believed by some that the poliomyelitis virus may enter the central nervous system along other peripheral nerves, in case these should be exposed at operations. Thus, the high incidence of the bulbar form of poliomyelitis after operations for removal of tonsils suggests infection from the throat along exposed nerves, especially as it is known that apparently healthy persons may harbor the poliomyelitis virus in the upper respiratory secretions and in the tonsils. It has been suggested that the seasons of high incidence of poliomyelitis (summer and early autumn) should be avoided for non-emergency operations on the throat or in mouth cavity. Poliomyelitis has been known to follow closely upon extractions of teeth.

Recently, it has been suggested that the virus may not enter by way of the nerves, but rather gains entrance to the lymphatic channels and then passes by way of the blood to the central nervous system.

Vaccines against poliomyelitis have not as yet been efficacious. For treatment, serum from convalescents from the disease has been tried; but after symptoms have already developed, it does but little if any good. Though second attacks of poliomyelitis are rare, four second attacks were observed in New York in 1935, thus indicating that one attack does not always confer immunity.

By the use of an artificial respirator known to the public as an 'iron lung,' many poliomyelitis patients who would otherwise die because of paralysis of the muscles used in breathing can be kept alive for an indefinite period, some of them gradually regaining power in the muscles of respiration. In England, a motor magnate, impressed by the value of such respirators, has given a large sum of money to provide them in hospitals throughout his country. In Sweden, another type of respirator has been devised; it encloses only the thorax and the abdomen, leaving the rest of the body free and thus facilitating nursing care.

The large amounts of money contributed to the National Foundation for Infantile Paralysis on anniversaries of the birthday of President Roosevelt (himself a survivor of poliomyelitis) will go far toward increasing research regarding the disease as well as toward providing ever better treatment for those who become crippled by it.

From the St. Louis Type of encephalitis, from the Japanese. Type B, encephalitis, and from human encephalitis occurring where equine encephalomyelitis was prevalent, specific virus strains have been isolated. The recognition recently of a series of cases of equine encephalomyelitis in pheasants in Connecticut is illuminating; since it is now known that several varieties of migratory birds are susceptible to certain strains of the virus, its wide distribution may easily be accounted for. The designation 'equine' may be a misnomer.

After proof was established that in Cuba and adjacent regions a special form of mosquito prevalent there was the cause of the spread of the yellow-fever virus, the disease was soon exterminated by screening all cases of yellow fever and by eliminating the offending mosquito vector by the draining or oiling of all standing water.

Though, in most countries, the mosquito known as Aëdes aegypti is the most important vector (carrier) of the yellow-fever virus, it has been shown that a number of other mosquitoes in the forests and jungles of South America (especially Brazil) may harbor the virus and probably transmit it, since no less than twenty rural epidemics have occurred in the absence of Aëdes aegypti. The problem of yellow-fever control is thus rendered more complicated than had been supposed.

The possibility of the introduction of a disease into a country by airplane through the carrying of insect vectors from a place in which it is rife, is now seriously considered, since a new type of malaria was thus brought from Africa to Brazil. It is feared that yellow fever, hitherto confined to tropical America and Africa, may be thus transplanted to Asia. The great intercontinental airlines are experimenting with methods for killing all insects on airplanes. It is reported that a liquid distillate (from a variety of pyrethrum) used as a spray will kill all insects (including mosquitoes and Tsetse flies) within a few minutes, although the vapor is harmless to man.

For prevention of this virus disease, injections of placental golbulin extract (placimmunin) is used by many when the disease is epidemic. Others maintain that the injection of convalescent serum is of equal value for prevention.

The pneumonias and tuberculosis are spoken of above.

It has recently been shown that these are initiated by an especial cultivable filtrable virus that is demonstrable in the secretions of the upper respiratory tract; though, after the initial infection has occurred bacterial infections that increase the severity of the cold and are responsible for complications may be superimposed. Chilling of the whole body, or of parts of the body, predisposes to the infection, as does living in dry overheated rooms.

In the treatment of the uncomplicated common cold, a hot bath, immediate rest in bed for one or two days, and hot drinks are of more benefit than anything else. Medicinal treatment by mouth is also used. Intranasal treatments, much resorted to, are better avoided, though the cautious inhalation of vapor produced by a mixture of compound tincture of benzoin and boiling water will have a local soothing effect.

In persons subject to recurrent colds, the paranasal sinuses should be suspected, as well as infected adenoids or tonsils. After local infections have been overcome, the so-called 'cold vaccine,' consisting of a sterilized mixture of the several bacteria most commonly met with in infections of the upper respiratory tract, may be used in prevention. Though comparative control tests give but little if any experimental evidence of the value of such vaccines, clinical experience of persons subject to recurrent colds and bronchitis who appear to have been markedly benefited by the use of such vaccines would seem to outweigh the negative experimental evidence.

Some believe that unsaturated fatty acids (chiefly linoleic and linolenic acids) in the form of so-called 'vitamin F,' for seven weeks, are effective in the prevention of colds.

This disease, formerly thought to be due to the Bacillus influenzae (Hemophilus influenzae), has since 1933 been known to be initiated by an especial filtrable virus that differs from the virus that initiates the common cold in that it is pathogenic for ferrets. That the Haemophilus influenzae acts synergistically with the virus to increase the severity of the infection and to cause complications seems probable. Attempts to prepare a satisfactory immunizing agent against this virus have thus far been unsuccessful, though persons vaccinated with a mouse-strain of influenza virus develop some immune substances in their sera and seem to acquire increased resistance to influenzal infection. Ferrets receiving repeated inoculations of influenza virus develop a cell-resistance to infection in the mucous membranes of the nose. The virus of common colds can be cultivated under aërobic conditions, whereas that of influenza requires anaërobic conditions.

Though most patients can be satisfactorily relieved by protection from substances to which they are allergic (or by desensitization to specific allergens) and by the use of injections of epinephrine or ephedrine in attacks, the use of so-called 'slow adrenalin' (epinephrine dissolved in defatted peanut oil, 1:500) yields a prolonged effect.

A few exhibit constant and intense dyspnea, not relieved by these methods. In such persistent and intractable asthmatic paroxysms, avertin with amylene hydrate, cautiously administered per rectum, will make the patient sleep for from one to six hours, after which he may remain free from asthma for days or even weeks.

This may depend upon (1) primary or essential hypertension, or (2) secondary hypertension due to various diseases (renal, adrenal, arterial, or thyroid).

In the treatment of essential hypertension, medical measures (partial rest, diet, elimination of stresses and strains, abstinence from tobacco, mild sedatives, and psychotherapy) are sufficient for the majority of cases; though in rapidly progressive and 'malignant' forms, surgical procedures (especially extensive subdiaphrag, matic sympathectomy) may be justifiable in younger patients to give symptomatic relief and to slow the progress of the disease.

The most important recent advance lies in the demonstration of vasa vasorum to the intima and inner media of the arterial coats in certain regions. It seems probable that this holds true for all regions. Injuries, especially occlusions of these vessels, may account for the development of the lesions in arteriosclerosis.

Improvement in the treatment by electrothermic coagulation has recently been reported. The amount of wire to be introduced is determined by the velocity of the blood current rather than by the size of the ancurysm.

Enthusiasm for surgical methods of treatment of the severer forms (cervical sympathectomy; section of dorsal nerve roots; thyroidectomy) seems to be waning. The majority of patients and physicians lean to the more conservative medical therapy.

In coronary thrombosis, many lives can be saved by the temporary use of morphine, complete rest, and restricted diet for a period of two months or longer, until the leucocytosis disappears, the sedimentation rate returns to normal, and the infarcted area has had a chance to heal. After this rest period, activities are cautiously resumed. Tobacco is prohibited.

This disease, formerly so devastating, can now be satisfactorily controlled by the use of stomach-treated liver extract (intrinsic and extrinsic factors) given orally or, better, by intramuscular injections. If spinal cord symptoms (funicular myelosis) are present, vitamin B₁ is given in addition.

For the hypochromic anemias, ferrous sulphate in the form of feosol tablets is at present the medicament of choice.

These diseases are as yet incurable. In chronic cases, some amelioration is obtainable by the application of high voltage X-rays or of radium (especially in Hodgkin's disease).

BLOOD TRANSFUSIONS. In large cities, so-called 'blood banks' are arranged for by hospitals and the Red Cross, in order that donors for blood of different types may be ever available for emergency transfusions. Careful controls of the donors by physical examination and Wassermann tests, and accurate blood typing are essential.

Patients require adequate treatment. Bed rest, intramuscular injections of extract of whole liver, oral administration of ferrous sulphate, and the use of a diet high in protein (raw meat and milk) and relatively low in carbohydrates and fat are effective measures.

Medical treatment (rest, Sippy's diet, vitamin C, and aluminum hydroxide gel in water by constant drip method at first, followed by oral method later) should be tried in non-emergency cases before resort to surgery (gastro-enterostomy; subtotal gastrectomy; celiac ganglionectomy with adrenal denervation).

The remarkable results in gastric ulcer, reported recently by Texas physicians, from the use of a snuff prepared from the posterior part of the pituitary gland inhaled four times a day await further clinical trial before judgment as to their value can be made.

In severe hemorrhage from an ulcer, and in acute perforation complete rest, dilaudid with atropin injected hypodermically, a partially-filled ice bag on abdomen, repeated small transfusions and treatment for shock may suffice. The blood pressure, pulse rate, hemoglobin, and blood urea should be closely followed. If response to medical treatment is not favorable, operative intervention is indicated.

Meningitis and poliomyelitis have been referred to under Infectious Diseases.

This is a disease causing varying degrees of paralysis, tremor, disturbance of speech, and nystagmus. Results of treatment continue to be unsatisfactory. Recently, intragluteal injections of blood serum from healthy donors beyond 50 years of age have been tried, and their influence reported as favorable.

Until lately, physicians have relied chiefly upon stramonium, atropin, or scopolamine for symptomatic relief. The effects of these drugs have been found to be enhanced if benzedrine is used in addition. This drug should not be used in patients who have high blood pressure, coronary disease, or an idiosyncrasy for the drug.

Claims made of the great advantages of Bulgarian belladonna as compared with other varieties in the treatment of Parkinsonism have not been substantiated.

Attempts to shorten the duration of primary depressions with hematoporphyrin (photodyn) and other substances, though sometimes followed by improvement, have yielded no conclusive demonstration of their value; the incidence of improvement is probably no higher than that expected from spontaneous remission. Injections of photodyn sometimes cause multiple neuritis.

Reports of the effect of administration of large doses of female sex hormones (theelin, estrogen, estradiol benzoate) in melancholias of the climacteric period are conflicting. Though improvement has followed the injection in some cases, no betterment has been observed in others.

The therapeutic nihilism with regard to dementia praecox was only slightly lessened by the application of re-educative methods to overcome bad habits and stereotyped mannerisms. About four years ago treatment by 'insulin-shock' was introduced, and since then psychiatrists all over the world have tried to evaluate its effects as well as those of other forms of irritative therapy. Judgment as to the justifiability of the use of these newer methods and their efficacy is best deferred for the present.

These 'shock' methods are now being tried also in the treatment of manic-depressive psychoses.

In the diagnosis and treatment of these, gratifying progress continues to be made. Most of the important endocrine substances (hormones) have been isolated and their molecular constitution determined; many of them can now be manufactured synthetically.

(Pituitary Gland). This organ, with its anterior, intermediate, and posterior lobes, has been shown to occupy a central place in the hormonal economy of the body. Its products influence the activities of other endocrine organs, and the substances produced by the latter may in turn influence the hypophysis. All the hypophyseal hormones appear to consist of proteins, or of long chains of amino-acids.

The products of the anterior lobe that influence other glands of internal secretion are designated 'adenotropic hormones.' They include gonadotropic, thyreotropic, adrenalotropic, pancreatropic, lactotropic, and parathyreotropic hormones, as well as hormones that influence general growth and development and others that influence the metabolism of carbohydrates and fat.

Over-activity of the anterior lobe is believed to be responsible for acromegaly (progressive enlargement of head and face, hands and feet) and gigantism (excessive size of body), whereas under-activity of this lobe is the cause of dystrophia adiposogenitalis.

Injections of anterior-lobe extracts have been much used to promote normal growth of the sex organs when they are under developed.

In the intermediate lobe two hormones (intermedin and melanophoren) are produced; they seem to be important for pigment metabolism.

In the posterior lobe at least three hormones are produced: (1) oxytocin (or pitocin), used to stimulate uterine contractions in obstetrical practice; (2) vasopressin, that increases blood-pressure; (3) an antidiuretic hormone that is important in the regulation of the water economy of the body (prevention of diabetes insipidus). The latter two hormones are both present in the commercial preparation known as 'pitressin.'

The most important hormone produced by the cortex is cortin (not yet obtained in pure state); it, like choline, is a powerful stimulant of the vagus nerve and is necessary for life. The principal hormone produced by the medulla is epinephrin (adrenalin), a powerful stimulant of the sympathetic nervous system raising blood-pressure and causing contraction of smooth muscle, except that of the bronchi, throughout the body.

Severe insufficiency of the whole of the adrenal system is responsible for Addison's disease. Over-activity of the cortex (due to tumors or hyperplasia) is responsible for pseudo-hermaphroditism, for premature puberty, and for virilism with hirsutism. Over-activity of the medulla (due to tumors or hyperplasia) may be the cause of arterial hypertension.

Since the discoveries of the relationship of over-activity of the thyroid gland to Graves' disease and of the responsibility of under-activity of the thyroid for Gull's disease (myxoedema) and for cretinism, intensive studies of the chemistry of the gland have yielded important findings. Determinations of the basal metabolic rate have been found to be very important for the diagnosis of over-activity or under-activity of the gland.

The iodine compound of the thyroid gland has been studied carefully (especially thyreoglobulin and two of its constituents — thyroxin and diiodotyrosin). Thyroxin and diiodotyrosin can now be prepared synthetically, but these substances do not exert their full effect except in a peptide combination. In the treatment of thyroid insufficiency, therefore, the use of desiccated thyroid is preferable as a rule to the use of thyroxin alone.

Whether certain substances that have been found experimentally to inhibit and suppress thyroid function, 'bridling substances' or 'katethines,' will prove to be useful in the treatment of mild hyperthyroidism awaits further clinical determination.

the main function of these glands is to regulate calcium metabolism. It has been known for some time that tetany (with hypocalcemia) is due to parathyroid insufficiency (curable by administration of parathyroid hormone) and that hyperfunction of the parathyroids may be due to adenomatous tumor of one of the glands, curable by surgery. Since the isolation of parathormone, it has been studied chemically and found to be a non-crystallizable protein substance containing about 15 per cent of nitrogen. Certain products of ergosterin (obtained by radiation) have properties similar to those of parathormone.

These glands produce the insulin that is so important for the regulation of carbohydrate metabolism (control of production of sugar from glycogen in the liver). Insufficiency of the insular apparatus is followed by diabetes mellitus (with hyperglycemia and glycosuria). In hypertrophy or adenomatosis of the insular apparatus, states of hyperinsulinism may arise, leading to a low sugar level in the blood; in such spontaneous hypoglycemic states, the patients become drowsy, and may suffer from fainting spells or convulsive seizures.

Insulin has a very complex molecular structure, composed exclusively of amino-acids. In pure form the hormone has an activity of 25 international units per milligram.

Insulin exerts its maximal blood-sugar-lowering effect in from two to three hours. Recently, a useful modification of insulin has been prepared by adding to it protamin and a zinc salt. This 'protamin zinc insulin' (which is given by subcutaneous injection only) has a much more prolonged blood-sugar-lowering effect (maximal in from 12 to 24 hours after administration). In some diabetics, insulin alone suffices for treatment; in others, protamin zinc insulin alone, while in still others, the combined use of the two preparations yields the best results.

(Sex Glands). At least seven natural follicular hormones (oestrone group) have been obtained in crystalline form. Chemically, they are closely related to sterins and can be synthesized from ergosterin. A rich source of these follicular hormones is the urine of pregnant women, the placenta, or the urine of stallions. The three best known follicular hormones are (1) theelin (ketohydroxy-estrogenic hormone), (2) theelol (trihydroxy-estrogenic hormone), and (3) alpha-estradiol — the most active one.

The corpus luteum hormone is known as progesterone. Its administration by injection is being tried to prevent threatened abortions and in the treatment of menorrhagia and metrorrhagia.

Four natural male sex hormones have been isolated, two of them (androsteron and dehydroandrosteron) from male urine, two of them (androstandion and testosteron) from testicular extracts. Of these, testosteron (in the form of propionate or valerianate) has by far the highest activity.

A whole series of important vitamins have been isolated. Among these, vitamins A, D, and E are soluble in fats; vitamins of the B-complex and vitamin C are soluble in water. Well-balanced diets contain adequate supplies of all vitamins; deficiencies develop when dietaries are deficient, or when vitamins are destroyed in certain diseases.

Man needs from 3 to 5 mg. of vitamin A daily to keep the functions of the epithelial cells normal and to promote growth. In deficiency, xerophthalmia, night blindness and skin lesions may develop, digestive functions may be impaired, growth may be retarded, and resistance to infections may be lowered.

Though vitamin A has been isolated, crystallized, synthesized, and its structural formula determined, the body supply is derived from foods that are rich in precursors of vitamin A (provitamin). It is abundant in cream, butter, liver and fish liver oils, egg yolk, and certain vegetables (carrots, tomatoes, wheat germ, greens). Of the precursors of vitamin A, three isomeric carotenes (alpha, beta, and gamma) and cryptoxanthin are the more important. The vitamin A activity of 0.6 micrograms of beta carotene has been adopted as the international unit. Adults require from 3,000 to 4,000 of these units daily; during pregnancy and lactation, a woman should receive 9,000 international units per day.

The vitamin B complex is now known to include a large number of different vitamin-factors, probably as many as ten. Yeast, wheat germs, tomatoes, greens, beans, peas, and liver are foods rich in B vitamins.

B₁ or F (thiamin, or aneurin) is of value in the prevention and cure of beriberi and in the treatment of alcoholic neuritis. The international unit corresponds to about 1.80 gamma of crystallized vitamin (free base). From 200 to 400 such units are required daily by normal adults. Beriberi in the Orient is very common, as a result of the polished-rice diet; for, in the polishing, the vitamin-containing surfaces of the rice granules are removed.

What was described as B₂ has turned out to be a complex of several substances, including lactoflavin (riboflavin), that is necessary for growth in chicks and rats; a P P factor, that prevents human pellagra; a factor, anti-perniciosa principle, or Castle's extrinsic factor, that is concerned in the prevention of pernicious anemia; a factor, B₁, necessary for normal nutrition of pigeons; a factor. B₁, that prevents disturbances of the muscles, heart, equilibrium, and growth in rats and chicks; a factor, B₂, necessary to maintain the weight of pigeons; and a factor, B₄ or H, for the prevention of a dermatosis in rats known as 'rat pellagra.'

Recently, the administration of nicotinic acid, which cures 'black tongue' in dogs, has been found to be very quickly effective in curing human pellagra.

As a specific in the treatment of pernicious anemia, a liver-stomach concentrate known as 'extralin' resulting from the interaction of liver extract (containing extrinsic factor) with stomach tissue material (containing intrinsic factor) is now widely used.

Deficiency of vitamin C (1-cevitamic acid; 1-ascorbic acid) is the cause of scurvy through injury to the endothelial cells of the capillaries and to colloidal intracellular substances. Human adults normally require more than 25 mg, (preferably 50 to 60 mg,) daily, if latent avitaminosis is to be avoided; infants should receive 20 mg., and children 40 mg, daily. Orange juice, lemon juice, grapefruit, lettuce, raw cabbage, and tomatoes contain C; green peppers, gladioli, iris and yucca are rich in C-content. The international unit of this 'antiscorbutic vitamin' is 0,05 mg, of pure cevitamic acid (equal to 0.1 cc, lemon juice). Latent deficiency can be recognized by quantitative determinations of the amount present in the blood, since with adequate intake (at least 250 units) of the vitamin the blood contains about 13 mg, per liter; when the blood is oversaturated, vitamin C appears in the urine. When persistent vomiting or diarrhea prevents utilization of adequate amounts taken orally, sodium cevitamate may be given parenterally.

Vitamin D. the 'antirachitic vitamin,' is a collective name for at least four different substances (D₁, D₂, D₃, and D₄); in addition, provitamins of the D group are known to occur in nature. The vitamin is abundant in fish oils and in egg-yolk. Vitamin D is essential for the maintenance of normal levels of calcium and phosphorus in the blood, and for the prevention of rickets, osteomalacia, and, perhaps, of dental caries.

D₂ (calciferol, new) is obtainable by ultraviolet irradiation of ergosterol; it has been prepared in crystalline form. D₁ is a molecular combination of D₂ with lumisterin. D₄ is 7-dehydrocholesterin less one atom of hydrogen; it seems to be identical with one of the vitamins in cod liver oil and possesses an activity identical with that of D₂. D¹ is an irradiation derivative of 22-dihydroergosterol; its activity is about half that of D₂. Still other forms of vitamin D are now known.

One international unit corresponds to the activity of one forty-thousandth part of a milligram of crystallized D₂. Sucklings require a daily intake of from 3,375 to 4,500 international units of D (corresponding to 15 or 20 drops of viosterol in oil).

Knowledge concerning vitamin E. the 'antisterility vitamin,' is still lacking in precision, though habitual abortions and the tendency to premature births may be due to the deficiency. It is contained in wheat-germ oil and cotton-seed oil; it may be identical with the alcohol known as alpha-tocopherol. Commercial concentrates of E are available under the trade names of Vitamin E Promonta, fertilol, and evion.

In rats, lack of this vitamin (influencing fat metabolism of the skin) gives rise to a form of dermatitis known as rat-pellagra or rat seborrhea, which is strikingly similar to (but somewhat different from) the so-called status seborrhoicus of man. The vitamin is present in liver, kidney, brain, brewer's yeast, casein, and potatoes. There is very little in milk, and almost none in meat.

Lack of this vitamin (sometimes designated C₂) may be the cause of severe broncho-pneumonia in young guinea pigs, preventable by lemon juice. Its significance, if any, for human pathology is unknown.

A deficiency of Vitamin K, the coagulation vitamin, in the food intake may give rise in animals to subcutaneous and intramuscular hemorrhages, the clinical picture resembling that of scurvy, though it is not curable by vitamin C. The marked prolongation of the blood-coagulation time is a striking characteristic. The vitamin is present in pig's liver, egg-yolk, alfalfa, and certain cereals; it may be a constituent of prothrombin since from the blood plasma of K-avitaminotic animals no prothrombin can be precipitated by acetone or acetic acid.

Concentrates of vitamin K would seem worthy of trial in the hemorrhagic diseases of man. In biliary obstruction with jaundice, vitamin K (200 mg.) and either whole human bile or large doses of bile salts may be given daily to prevent the development of hemorrhagic tendencies.

Vitamin P is known as the 'permeability vitamin,' since it lessens the permeability of the walls of the capillary blood vessels. In certain diseases (e.g., the vascular purpuras) in which this permeability is increased, pure vitamin C is not preventive, whereas substances (paprika extract and lemon juice) containing vitamin P are therapeutically effective. Chemically, vitamin P seems to be a flavano-glucosid known as 'citrin' (a mixture of glucosides of hesperidin and eriodictyol).(See section on Vitamins below)

Intensive researches upon the origin of cancer and other tumors are being continued. Among the more interesting current developments are (1) the successful transplantation of human cancer into the anterior chamber of the rabbit's eye; (2) the demonstration of the affinity of certain forms of ultra-filtrable virus for tumor tissue (symbiosis of virus and tumor); (3) the production of tumors in animals by transforming normal cells into cancer cells by means of chemical agents (polycyclic hydrocarbons like benzanthracene compounds).

The most interesting developments in the treatment of cancer during the year are those connected with the use of the recently-discovered neutrons, minute atomic particles, which carry no electrical charge. These are most conveniently produced by the spraying of beryllium with high speed particles of heavy hydrogen. This breaks down the beryllium and sets free the neutrons from the nucleus. Small quantities can be produced in a variety of ways. Neutrons were discovered by exposing beryllium to the action of radium radiations by Irene Joliet-Curie and her husband and were at first thought to be a variety of X-ray because they penetrated thick layers of lead which stopped all the charged particles. Being uncharged, they slip through the crannies between the lead molecules and only cause a disturbance when they make a head-on collision. Large quantities of neutrons can be best produced by an apparatus known as a cyclotron invented by E. O. Lawrence of the University of California. For this purpose electrically charged particles of heavy hydrogen gas circulate in a circular channel and are given a push by an electric impulse as they pass a particular spot in the tube. When the pushes are synchronized with the passage of the particles the latter can be stimulated to an enormous final speed. The hydrogen particles being charged, their path can be controlled by a powerful magnet which keeps them in their circular course. Finally, when a suitable speed is reached, neutrons are allowed to escape and strike the beryllium. The neutrons which are set free, not being charged, cannot be controlled by a magnet nor can they be cut off by lead of any ordinary thickness; instead, large blocks of paraffin stop them more easily than does lead, so that this substance and concrete in very great thickness are used to protect the bystanders. When such a beam of neutrons enters the tissues of the body they go a considerable distance without causing damage, and then strike, especially as they lose speed, the atoms which compose the tissues and send forward a shower of electrons which, being charged particles, cause serious damage in the tissues by their absorption, just as do the negatively-charged particles from X-ray and radium. It is also possible that the neutron enters the nucleus to form an unstable atom which rapidly breaks down, giving off a variety of rays and particles. It is hoped by the use of these neutrons to avoid damage to the skin and treat more effectively tumors inside the body than is at present possible with X-ray or radium. Very cautious tests are now being made on human patients with cancer to see whether the practical results correspond with the theoretical assumptions. It will take a long time to find out because it is generally assumed necessary to wait five years before considering a cancer patient as cured.

Another interesting investigation has been made in the Crocker Laboratory, Columbia University, New York, using a million-volt machine constructed in cooperation with the Presbyterian Hospital, to explore the possibilities of improving the results of X-ray treatment of cancer by raising the voltage up to about a million. A very interesting conclusion has been reached by the research staff of this institution that no practical advantage occurs from the use of voltages in excess of 700,000, so that no further increase in electrical pressure above that point need be considered in the treatment of cancer. This is very satisfactory from a practical aspect because the costs of the apparatus at the lower voltages are vastly less than that of a million-volt machine, and the case of running is much greater.

The extraordinary discoveries made in the last ten years concerning the chemistry of certain fairly simple benzol compounds capable of producing cancer in man and animals are being continually added to by the labors of a large number of chemists. The door was opened years ago, mainly by Kennaway, head of the research laboratory of the Cancer Hospital in London, who showed that by passing acetylene gas through a hot glass tube a compound carcinogenic for mice could be produced. This suggested that the carcinogenic compound in tar and shale oil, which have for many years been known to be responsible for cancer in man, presumably contained only carbon and hydrogen, as does acetylene. The further chemical study of coal tar which literally contains thousands of compounds led to the separation of a group of substances known as anthracenes. The first of these isolated and studied by Cook, a research chemist at the London Cancer Hospital, was 1:2:5:6-dibenzanthrene. This was found to cause abundant cancer in mice. From his investigations of this chemical, Cook drew certain conclusions as to its structural constitution. He showed that, through simpler, 1:2-benzanthracene was not carcinogenic. He also showed that a number of more complicated derivatives were not carcinogenic, and that a change in position of the radicals connected with the benzol ring would produce compounds less active than the 1:2:5:6 substance. Cook then isolated from a number of tons of coal tar a few grams of a substance identified as benzpyrene and closely related to dibenzanthracene. This proved to be even more active in the production of cancer than the compound first mentioned. A third substance also discovered by Cook is methylcholan-threne. This can be derived from the bile acids secreted in the human gall bladder and also can be produced from cholesterol. In other words, it is a substance which might be produced in the body as its antecedents occur there. A large number of other chemists, notably Fieser of Harvard, who has written a monograph on this group of phenanthrene compounds, have busied themselves in studying the nature and possible modification of the carcinogenic properties of this large group of substances.

Finally it was shown, chiefly through the work of E. C. Dodds, that there was a close cross linkage in structure between the carcinogenic agents, the male and female sex hormones, and some of the vitamins. Thus chemistry has begun to throw light on substances which are known to have produced some rare types of human cancer. The next step must be to find those chemicals which produced other kinds of cancer, such, for example, as that of the stomach, in order that means may be found either to prevent such formation or to neutralize the compound if formed. While the different kinds of cancer may have different causes, the fact that a single chemical substance has produced cancer in nearly all the organs of the body in animals and also a great variety of types suggests that the number of such causative agents may perhaps be few.

Interest in fever therapy has continued to be active during the year of 1938. More and more hospitals are coming to use this method of treatment — this in spite of the fact that one of the major indications for its use, namely, gonorrhea in both sexes, has come to be treated widely by the drug called Sulfanilamide. This pharmacologic method of approach is simpler than the use of physically induced fever. However, the large percentage of failures in the treatment of gonorrhea by means of the drug and the very considerable number of individuals who appear to respond badly to its administration indicate the need for the application of physically-induced fever for the cure of this condition. To enhance the effectiveness of sulfanilamide administration and to remove partially the disadvantages of prolonged fever sessions with the maintenance of high temperatures, efforts have been made to combine the use of these two agencies simultaneously. This has been one of the outstanding developments in fever therapy during the year.

Further reports have been made as to the effectiveness of artificial fever in the care of pelvic inflammatory disease due to gonorrhea and to other forms of this disease.

Diseases of the eye such as gonorrheal ophthalmia and conjunctivitis, syphilitic interstitial keratitis, iritis, and scleritis have been reported as favorably influenced by fever therapy. There has been a lack of success with uveitis and trachoma.

Attention was again called to the value of physically-induced temperature elevation in the treatment of undulant or Malta fever. The results suggest that this form of therapy is most effective in the acute or subacute stages of the disease.

Amongst skin conditions, dermatitis herpetiformis was found to be an additional indication for fever therapy. In a case of septicemia due to the meningococcus, hyperthermia caused improvement in spite of failure to influence the disease by the commonly employed specific serum.

A study of the psychiatric aspects of artificial fever showed that in about 400 patients, fever exaggerated the subject's outstanding personality characteristics. Through the application of psychotherapeutic measures, the limitation of sedatives, and increased experience, it was possible to reduce the incidence of delirium when employing high temperatures for a long time.

The discussion as to the best method of inducing fever by physical agents was continued during the year. Elevation of body temperature can be accomplished by external application of heat such as the hot water bath, water sprays, and heated air, or by means of electric currents which are converted into heat within the body. These currents are produced by the diathermy machine (which has been largely replaced) and by the apparatus producing short-wave currents. Some doctors consider this latter method safer and more comfortable for the patient. It would appear that many physicians are combining the use of these two procedures. Most of the cabinets for the production of fever therapy displayed during the year included some device for the humidification of the air within the cabinet. This is in response to suggestions made as a result of experiments that highly humidified air is more effective and less distressing to the patient than dry air.

The literature contained further reference to the continued use of fever therapy for the treatment of general paralysis of the insane, arthritis both of the gonorrheal and of the more frequent infectious variety, multiple sclerosis, asthma, and Sydenham's chorea.

The possibility that it is best to give a series of brief treatments at comparatively low temperatures before administering high temperatures for prolonged periods of time was pointed out. It was shown that the total volume of blood in the body can be increased by gradual exposure to heat and that the great loss of fluid from the body during fever treatment causes a lowering of the total blood volume.

Radiotherapy is the application of X-rays and radium rays to the treatment of disease, and dates back to the end of the last century.

Shortly after the discovery of X-rays by Konrad Roentgen on Nov. 8, 1895, physicians began using X-rays to photograph the inner structures of their patients. They would repeatedly test the penetrating power of the radiation by the appearance of their hands when exposed to the X-rays. After a time the skin, which was thus repeatedly irradiated, began to show changes. It lost its normal covering of hair, became red, and, in more severe instances, even became ulcerated. This depilatory effect of X-rays led Doctor Leopold Freund of Vienna to try X-rays for epilation of a hairy birthmark in November, 1896. It was a short step from this first successful experiment to the general application of X-rays for treatment. First this was limited to skin diseases, but soon thereafter X-ray treatment was being applied to various ailments, including cancer. In the beginning, X-ray therapy was thought to be a new panacea, though it was not long before the limitation of this treatment became apparent.

The X-rays used for treatment are similar to those used for taking X-ray photographs. The difference is that, for treatment, smaller quantities of more penetrating X-rays are usually employed. Penetration is governed by the voltage. Thus one speaks of low voltage, if it is less than about 110 kv.; medium, if the voltage lies between 120 and 150 kv.; high, if it varies between 160 and 200 kv.; and supervoltage, if it is higher than 250 kv.

Soon after Pierre and Marie Curie had isolated radium in 1898, their friend, Becquerel, borrowed a small quantity of it for experimentation. He placed this in his vest pocket, where he carried it in close contact with his body for several days. Shortly thereafter, he noted a small burn on the skin which had been near to the radium. Becquerel recognized the similarity of his own burn with X-ray burns he had seen in patients and at once thought of the therapeutic possibilities. He communicated his observation to his medical friends. Soon thereafter French doctors were using radium for the treatment of skin diseases, and various other ailments including cancer.

Radium is an element which is found in nature in combination with uranium. It is continuously disintegrating and gives off an inert gas, radon. Biologically, radon acts like radium and is at times used in place of radium for treatment. The usefulness of radon, however, diminishes rapidly, while that of radium remains. It takes 1,750 years to use up half of the radium and only four days to use up half of radon. Radon or radium continuously emits so-called alpha, beta, and gamma rays. The latter are used mainly for the treatment of disease and act biologically like very penetrating X-rays. Radium may be thought of as a small, constantly-working X-ray tube. In treating disease, it is used chiefly where the diseased area is small and the part to be treated is easily accessible, e.g., on the surface or in an open body cavity. More rarely, and if large quantities are available, radium is used also to irradiate deeper locations through the skin. X-rays may be used similarly, except in small body cavities, where radium seems preferable. Portions of the mouth and other body cavities may be irradiated with X-rays directed through lead-protected cylinders. In treating more extensive and less accessible areas, X-rays are used for irradiation through the unbroken skin.

Radium is expensive, as the supply is limited and the cost of its extraction and purification is high. It used to be mined in Joachimsthal, Czechoslovakia, in Colorado and Utah in the United States, but more recently has been obtained chiefly in the Belgian Congo and in Northern Canada. As increasing deposits of uranium have been discovered, the price of radium has gradually dropped from $125 a milligram a few years ago to about $25 a milligram at present.

Normal and sick tissues are injured by X-rays and radium. The latter, however, have less resistance and succumb more readily than the former. For this reason it is possible to destroy sick tissues without similarly damaging the normal tissues which surround them. In place of mechanically lifting out the diseased tissue as is done by operation, radiotherapy destroys the sick cells in the midst of the surrounding healthy tissue. The destroyed cells must be absorbed by the body, unless the disease is situated on the surface or in an open body cavity where it may be thrown off.

All kinds of inflammations, over-active functions, and growths may at times be cured by exposure to radiotherapy. Thus, various skin diseases, goiter, excessive and abnormal bleeding in women, birthmarks in babies, and various cancers may often be successfully treated. But where sensitivity to irradiation is absent, radiotherapy is likely to fail.

The main progress in recent years, and especially in 1938, has been the gradual standardization of the indications and contra-indications for treatment with radium and X-rays, and the improvement in technique and in apparatus.

Larger quantities of radium for external application have been concentrated in single containers, in so-called 'radium bombs.'

More penetrating X-rays have been produced by raising the voltage of the X-ray machines up to one million volts.

Special progress has been made in the treatment of cancer of the mouth, throat, breast, and womb. As always, however, success in treatment of cancer still depends upon the extent of the disease when the patient is treated; the skill of the doctor applying the treatment; and, lastly, upon the apparatus available. The proper application of radium and X-ray therapy requires a great deal of study and experience and therefore should be entrusted only to physicians who have spent a sufficient time in preparing themselves for this work.

By 'socialized medicine' is meant collective methods of prevention or treatment of disease which is tax-paid in whole or part.

For many years socialized medicine has been an accepted method for the mass control of communicable disease, and public health departments have addressed successful efforts to such diseases as typhoid, smallpox, and tuberculosis, assisted by voluntary health associations whose funds are not derived from public funds. These efforts have concentrated on sanitary measures and popular education. Until the last few years it has not seriously been proposed to include the treatment or payment for treatment, of patients. The single exception has been in the case of the indigent who, to an increasing extent, at present have their doctor bills paid by the Government under various relief set-ups, though in the main the indigent patient is still a charge upon the beneficence of the private practitioner.

But in the year 1938 came an increasing demand for tax-paid medical care to include treatment not only of the indigent but of persons in the low income group, with extension of existing public health services. In July 1938, a Federal committee known as the Technical Committee on Medical Care met at Washington with representatives of various groups, including the American Medical Association. Five recommendations were proposed by the Government calling for a 10-year program at an ultimate cost of $850,000,000 per year at the end of the period. These proposals included expansion of the public health and maternal and child health services, the expansion of hospital facilities, provision of medical care for the medically needy, and suggested that, by use of the insurance principle or otherwise, persons in the low income group should be helped to pay the cost of medical care.

A special meeting of the House of Delegates of the American Medical Association was convened in September 1938, at Chicago. This was the third time in its history that a special meeting had been held. The Government's proposals were approved in general, with certain qualifications relating to adjusting them to ascertainable needs. Compulsory health insurance was denounced by resolution as a 'complicated bureaucratic system which has no place in a democratic state . . . that it would lend itself to political control and manipulation there is no doubt.' (Compulsory health insurance is financed by taxes on employer and employee, based on pay rolls, with a contribution by government.) In place of this, the American Medical Association expressed a conviction that 'voluntary indemnity insurance may assist many income groups to finance their sickness costs without subsidy.' Approved, also, was insurance for hospitalization, a method of pre-payment for hospital bills which is said to have grown in the last two years to cover more than 2,000,000 persons in the United States. At this session a committee of seven physicians was appointed to confer from time to time with Government officials looking toward adjustment of points of difference, largely questions of feasibility, between the medical profession and the Administration. There will probably be no agreement between the Government and the profession on the question of compulsory health insurance.

A rapid growth of medical expense indemnity insurance plans has occurred since the meeting of the American Medical Association at Chicago, in the main on a nonprofit basis, and providing for medical control of the medical practice given under them. Such plans are in process of promotion in New York State, California, Cleveland, Cincinnati, Washington, D.C., Denver, and a number of other places.

The Syphilis Campaign, which the United States Public Health Service inaugurated in the summer of 1936, met with notable popular support. Straw polls, conducted by the American Institute of Public Opinion, throughout 1936 and 1937 showed support of approximately 10 to 1 for adequate Federal appropriations for free public clinics, the establishment of adequate laboratory facilities for the diagnosis of syphilis, and other measures for control. A notable step forward was taken in May 1938, when the President signed the Venereal Disease Control Act.

This Act established a national policy of grants-in-aid for venereal disease control upon much the same basis as the Social Security Act had made funds available for general public health purposes. The same well-proven and successful administrative procedures were applied in the handling of these funds. The sum of $3,000,000 was appropriated by Congress for the year 1938-39, and the Act authorizes appropriations of $5,000,000 and $7,000,000 for the next two succeeding fiscal years. It contemplates that thereafter sufficient funds shall be appropriated to assist the states in effectively coping with this problem. The annual expenditure suggested by the conference of state and provincial health officers, which assisted in the drafting of the measure, was $25,000,000 for each of the succeeding ten fiscal years.

In working with the states, and in its educational campaign since this Act was passed, the United States Public Health Service has emphasized the fact that the most critical stage of the fight against syphilis is just beginning. Syphilis, as Senator LaFollette told the Senate Committee, 'must be fought on forty-eight fronts at once.' The movement of people across state lines makes effective local programs impracticable. Local leadership must now cooperate for the establishing of adequate facilities in every community and the securing of sufficient appropriations to develop those facilities to their point of maximum effectiveness. The outline of such a local venereal disease control program as recommended by the Conference on Venereal Disease Control, which met in Washington, in December 1936, is as follows:

(1) There should be a trained public health staff to deal with syphilis in each state and city.

(2) Minimum state laws should require reporting of cases, following up of delinquents, and the finding of sources of infection and contacts.

(3) Premarital medical certificates, including sero-diagnostic tests should be a legal requirement.

(4) Diagnostic services should be freely available to every physician without charge and should meet minimum state standards of performance.

(5) Treatment facilities should be of good quality, with convenient hours and location. Wherever possible the clinic service should be a part of an existing hospital dispensary. Hospital beds should be provided for patients needing bed care.

(6) The states should distribute antisyphilitic drugs to physicians for the treatment of all patients.

(7) Routine sero-diagnostic tests need to be used much more widely. In particular, every pregnancy, every hospital admission, every complete physical examination should include this test.

(8) The informative program in modern diagnosis, treatment and control should be prosecuted vigorously among physicians and health officers, especially through the use of trained consultants.

(9) The public education program must be persistent, intensive, and aimed especially at those individuals in the age groups in which syphilis is most frequently acquired.

Legislation requiring blood tests for syphilis before marriage has been passed by Connecticut, Illinois, Kentucky, Michigan, New Hampshire, New Jersey, New York, Rhode Island, and Wisconsin. In addition, as a measure for the prevention of congenital syphilis, which has annually taken a toll of 85,000 infants in the United States (60,000 born alive and diseased, and 25,000 stillbirths), the states of New Jersey, New York and Rhode Island require blood tests for every pregnant woman.

As revealed by research during the past thirty years, man and all the higher animals require a large number of dietary factors to maintain life and well-being. Among these are the substances referred to as vitamins. But other essentials no less important than vitamins are minerals, proteins, fats and carbohydrates.

Vitamins are organic substances widely distributed in nature and required by the body in very small amounts, as compared to the needs for carbohydrate, protein, fat and certain minerals. They play essential roles in the various functional activities of life, but in these functions there is no duplication of action. Rapid progress is being made in the characterization of vitamins through studies of their chemical properties and physiological roles. At present there are at least seven different vitamin groups known definitely to be required by man, and whose chemical properties are understood. These are vitamins, A, D, E, thiamin, ascorbic acid, riboflavin and nicotinic acid. In addition, it is highly probable that man requires vitamins B₆, K, certain unsaturated fatty acids, and several other factors which have not been characterized chemically.

Vitamin A (C₂OH₂₃OH) is anomalous in that it is found only in animal tissues, milk and eggs. Carotene and certain other carotenoids, yellow and orange pigments of carrots, yellow corn, pumpkins, green leaves and various other plant sources, upon ingestion by the animal body, are converted into the vitamin. Recent spectrographic evidence, supported by biologic evidence, indicates the existence of a vitamin A-like substance which is called vitamin A₂.

Little is known concerning the function of vitamin A. It is essential in preserving the functional integrity of all epithelial tissues such as the skin and lining of the gastrointestinal tract, urinary and genital tracts, and the retina of the eyes. Much interest prevails in the relation of vitamin A to certain visual disturbances, especially 'night blindness.' Since the visual mechanism is so sensitive to even slight degrees of vitamin A deficiency, it appears probable that the present investigations will evolve a satisfactory method of estimating mild degrees of deficiency by means of visual tests. Rich sources of vitamin A, or its precursors, are fish liver oils, milk fat, liver, egg yolk, leafy vegetables and carrots.

This is the term used to designate sterol-like substances which promote proper utilization of calcium and phosphorus, thus preventing rickets if the diet contains adequate amounts of the bone-forming minerals. Ten such antirachitic factors are known to exist, and probably there are more. Many of the chemical and physical properties of these substances are known. These factors are formed by certain rays (wave lengths) of sunlight, of artificial light, when directed upon certain 'non-active' sterols; hence the origin of the term 'sunshine vitamin.' The sterol in skin which becomes 'activated' upon proper irradiation is 7-dehydrocholesterol. Irradiation of ergosterol, a sterol of ergot and yeast, produces calciferol. This is the active substance in viosterol and 'irradiated' yeast. Most natural foods contain no vitamin D. Small amounts occur in eggs and butter. The principal convenient sources are fish liver oils, irradiated ergosterol and certain foods such as milk and yeast which have been properly irradiated.

Vitamin E (C₂₉H₃₀O₄), like A and D, is a fat-soluble factor. Evidence based largely on rat studies has shown that it is necessary for spermatogenesis and the maintenance of adequate placental attachment to the uterus during gestation. Male rats deprived of the vitamin for long periods of time become permanently sterile but the injury to females is repaired when the nutrient is provided. The factor is not exclusively related to reproductive functions since body growth is impaired and some degree of paralysis occurs in its absence from the diet. Probably there are several different compounds possessing vitamin E activity. The factor is found in the embryo of cereals such as wheat, corn and rice; vegetable oils and fats; lettuce and various other natural foods. Presumably most dietaries contain it in adequate amounts. Striking advances have been made during 1938 in the structural chemistry and synthesis of vitamin E.

Thiamin (C₁₂H₁₇N₄SOCl) is the term gradually meeting acceptance for the heat-labile factor formerly referred to as the anti-neuritic or anti-beriberi vitamin. Frequently it is called Vitamin B_1. It is required in a particular stage through which carbohydrate must pass in its conversion into energy (heat or work), or storage as fat. A deficiency of thiamin is manifested by peripheral neuritis and paralysis, emaciation, irritability, loss of appetite, and other symptoms. These are dramatically relieved when thiamin is restored to the diet. Since the body is unable to store thiamin in very large amounts, a deficiency may occur unless it is taken regularly. The outer layers of cereal grains, as well as the germ portion, are rich in thiamin. Legumes, leafy vegetables, fruits, nuts, liver, egg yolk and milk are good sources. Yeast is the richest natural source. Synthetic thiamin has been available for two years.

Ascorbic acid (C₆H₈O₆), or Vitamin C, is unique in that there are marked species-differences in requirement for it. Apparently it is needed in all forms of animal life but most species are able to produce it within their bodies. Only man, monkeys, guinea pigs and swine are known definitely to lack this ability and are, therefore, dependent upon food for the substance. The exact functions of ascorbic acid are not known but apparently it is involved in cell respiration. Scurvy occurs in conditions of gross ascorbic acid deficiency. This is characterized by typical changes in the bones and teeth, tenderness and some swelling in various parts of the body, especially the thighs, ulceration and bleeding of gums with loosening of the teeth, and purplish-black spots in the skin caused by broken blood capillaries. It is possible to estimate mild degrees of deficiency by means of chemical determinations of ascorbic acid in the blood and urine. Since the vitamin is readily oxidized it is largely destroyed by cooking. Citrous fruits and tomatoes are especially rich sources. It occurs in all fresh fruits and vegetables.

Riboflavin (C₈H₁₀N₂O₃) is a complex yellow compound with a characteristic green fluorescence. It is readily destroyed on exposure to light. Most of the knowledge concerning it has been obtained during the last five years. When combined with protein it appears to function as an enzyme in cell respiration. Frequently riboflavin is referred to as synonymous with vitamin G, but such usage is not justified. The term vitamin G was used originally to indicate heat-stable, water-soluble dietary factors necessary for growth and well-being in the rat. Some of these factors (riboflavin, vitamin B₆ and nicotinic acid) have been characterized chemically. Since riboflavin is an entity, it is obvious that the factor is not synonymous with vitamin G. The latter has only historical significance now, as respects modern nutritional usage. Milk, liver, eggs, yeast and leafy vegetables are good sources of riboflavin.

Nicotinic acid (C₅H₄N₁COOH), a long familiar compound, produces dramatic alleviation of several symptoms which characterize pellagra. In 1937, the substance was shown to be effective in curing black-tongue in dogs, a dietary deficiency disease believed to be analogous to human pellagra. This was quickly followed in 1938 by successful treatment of pellagrins with nicotinic acid. However, it is improbable that the symptoms of pellagra are due entirely to a deficiency of nicotinic acid since the diets of pellagrins are deficient in other dietary factors. But it is certain that a deficiency of nicotinic acid, or some close derivative, is involved in the etiology of pellagra. Swine, on a nicotinic acid-deficient diet, develop pellagra-like symptoms which are promptly alleviated by means of the substance. Six different derivatives of nicotinic acid have been shown to be effective in curing black-tongue in dogs. Little is known concerning the distribution of nicotinic acid. It is deficient in some cereal grains but apparently leafy vegetables, fruit, milk, liver, and eggs contain it in considerable abundance. Yeast is exceptionally rich in it.

At this close view of vitamin research during 1938 it appears evident that the two most outstanding contributions have been (a) the identification of nicotinic acid as a factor in the cure of pellagra and (b) establishment of the chemical structure of Vitamin E. Physicians and public health workers have exhibited greater critical interest in the problem of recognizing and correcting mild degrees of vitamin deficiency. A few useful books containing information on vitamins have appeared during the year. The most notable contribution has been the series of review articles on vitamins in The Journal of the American Medical Association.

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Medicine