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.

1939: Medicine

Progress in Medicine in 1939 continued its advances, with new methods of anesthesia, X-ray photography, treatment of infections and systemic diseases.

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Of the older anesthetics, chloroform is now, because of its highly toxic and depressive effects, but rarely used. Nitrous oxide gas and ethyl ether, alone or in succession, are still frequently administered and are reasonably safe, though ether is avoided in operations on the chest because of its irritating effects.

Prolonged spinal anesthesia produced by subdural injections of nupercaine (the potency of which is ten times that of cocaine and twenty times that of procaine (novocaine hydrochloride)) is now much used in properly selected cases. It is especially favored in genitourinary and rectal surgery in which a high level of anesthesia may be unnecessary and smaller doses of the anesthetic suffice. Still better results (greater anesthesia and more prolonged unconsciousness) are obtained in spinal anesthesia by using a little procaine along with the nupercaine. In some surgical clinics, the introduction of novocaine crystals into the cerebrospinal fluid is still preferred as a method of producing spinal anesthesia. Spinal anesthesia should be avoided in patients with severe heart disease, in patients with marked arterial hypertension or hypotension, and in general in all 'poor risk' cases.

When operations requiring the Trendelenburg position are to be performed, spinocaine instead of procaine may be used with the nupercaine.

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Among the newer anesthetics, avertin, cyclopropane, vinyl ether, evipal sodium, and pentothal sodium have been largely used.

Avertin (tri-brom-ethanol or rectanol) is given by rectum and is fairly safe in patients who do not suffer from diseases of the heart or kidneys. It is especially useful in nervous, anxious and excited patients. Many surgeons use it in operations upon the thyroid gland.

Cyclopropane is an anesthetic gas that, on inhalation, quickly produces unconsciousness and marked relaxation. Large amounts of oxygen may be given with it so that anoxemia during its use can be easily prevented. Its chief use has been in operations upon the lung and chest. The hazard of explosion is, however, great and in some hospitals the use of this anesthetic has been prohibited.

Vinyl ether (vinethene) is a liquid given usually by the open-drop method so that adequate amounts of oxygen are inhaled and anoxemia prevented. The patient becomes unconscious quickly and on coming out of the anesthesia has little or no nausea or vomiting. Its chief use is in minor surgery of short duration, in dental surgery, and in obstetrics.

Evipal sodium is a barbital compound which is often given intravenously for the production of a brief narcosis. It is not without its dangers and should be given only in hospitals and by persons skilled in its use. It has been praised as a desirable anesthetic for painless labor, for prostatectomy, and for operations upon the eye, as well as for some general surgical operations.

Pentothal sodium (another barbital derivative) is growing in popularity. It is given intravenously, preferably in 2.5 per cent solution, and 1.0 g. is a maximal dose. Before giving this anesthetic, an injection of atropine or scopolamine with or without a small amount of morphine is given to counteract parasympathetic overactivity. It is not advisable to use pentothal for patients under 15 years of age, or for persons suffering from disturbed respiratory function, severe anaemia, or gross hepatic damage. Pentothal has been used already in over 20,000 instances, particularly in general surgery, and urogenital surgery, but also in dentistry and in operations upon the eye, the paranasal sinuses and other structures.

Though the use of novocaine (procaine hydrochloride) as a local anesthetic has been the principal agent used by dentists during the past thirty years, a recently developed substance known as para-amino-mono-isobutyl benzoate hydrochloride is said to be still better. By means of it, any major dental operation can now be performed without any pain to the patient except that produced by the needle puncture. More than eight million injections of this drug have already been made; it produces local anesthesia swiftly and safely and may be used in patients who have heart disease.

Experiments upon animals conducted by the Bureau of Mines in 1929 showed that when oxygen-helium mixtures were used, the difficulties that are presented by inhaling ordinary air (oxygen and nitrogen) under high pressure could be overcome. When men under high atmospheric pressure inhale an oxygen-helium mixture instead of natural air, the time required for decompression without danger is greatly reduced, and, moreover, divers can descend to greater depths and work there safely for longer periods. The U. S. Navy adopted the method for divers who attempted to salvage sunken boats. Since a layman in 1937 invented a diving suit by means of which he could breathe oxygen and helium which he carried on his own person, it has become possible for a diver to work at a depth of 420 feet under water without injury.

Increasing attention is being paid to the anoxemia that develops at air-levels above 10,000 feet. No symptoms may be noted at first or headache, drowsiness, dizziness, difficulty in concentration, or feelings of lassitude, fatigue, or indifference may be experienced. Among pilots and airplane personnel and also among passengers who are at altitudes in excess of 10,000 feet at frequent intervals, anoxemia is almost certain to develop unless oxygen is used efficiently. Chronic anoxemia has a definitely deteriorative effect upon general functional capacity.

Fortunately, with the new B. L. B. oxygen inhalation apparatus, oxygen can be supplied simply, safely, efficiently and economically even at altitudes of 25,000 to 35,000 feet.

Since the onset of the symptoms of anoxemia is insidious, there might be great danger of impairment of the judgment and efficiency of a pilot with resulting accidents unless adequate oxygen supply were provided for.

On some air lines the use of oxygen on the part of the crew is now mandatory at any altitude over 10,000 feet, and though left optional for passengers they too are advised to use oxygen at high altitudes. The hostesses on airplanes are trained nurses and know how to instruct passengers in the application and use of the inhalation apparatus.

An oxygen tank containing 1,300 liters weighs 27 pounds (4 pounds oxygen, 23 pounds container) carried on the plane gives a sufficient supply as the B. L. B. inhalator is very economical in the use of oxygen.

Patients with heart disease have largely abstained from airplane travel because of the altitudes reached. With the use of oxygen as above described, ambulatory heart cases may now fly with relative safety.

It is interesting that in persons with a so-called 'hang-over' (Katzenjammer) in the morning following an alcoholic spree there is a pronounced anoxemia and the inhalation of oxygen (with or without helium) will give prompt relief. One physician has suggested that drug-stores may establish 'oxygen-bars' for the treatment of such 'hang-overs'; they might prevent resort to the harmful acetanilide and bromide mixtures now often taken by those who have imbibed too freely.

At a two-day conference held at the Academy of Medicine in New York City in November 1939 convalescent care in all its aspects was extensively discussed. The need for suitable convalescent homes for the further care of many patients before returning to their own homes after discharge from hospitals was insisted upon, but better provision for medical supervision than that now available in many of these convalescent homes was strongly urged.

A new method of X-ray photography by means of which clearer and more intense images are produced though less powerful X-rays are used, reducing the danger of burns to both physicians and patients, has recently been patented. The method involves photo-electricity, electrons and some of the basic principles of television.

Another advance in X-ray work was shown at the New York World's Fair. It consists of a rapid X-ray unit capable of photographing the chests of some 150 persons per hour at a cost of one dollar each instead of the ordinary charge of ten or fifteen dollars. The low cost depends mainly upon elimination of photographic films, the X-ray pictures being recorded directly upon sensitized paper. Such paper comes in rolls large enough for one hundred successive X-ray pictures of chests, each roll being developed like a large camera roll. The X-ray impression left on each picture by a lead card serves for identification. The method promises to be of great service in tuberculosis-control programs in the United States and in other countries. In certain groups of the population the incidence of pulmonary tuberculosis is high; thus an analysis of 150,000 chest X-rays made by WPA technicians among home relief recipients, prisoners, applicants for civil-service jobs and other groups showed that 4,500 persons (3 per cent of those tested) had active tuberculosis; 4,500 others showed traces of it.

Many patients who have to be subjected to X-rays for purposes of treatment develop so-called 'radiation sickness.' It is reported that this can be prevented by the administration of nicotinic acid in powder form to the patient before the X-ray treatment. See also RADIO.

In patients who suffer from many severe attacks, the subcutaneous injection of so-called 'slow epinephrine' (either in the form in which powdered epinephrine base suspended in peanut oil is used or in the form in which the epinephrine is dissolved in a gelatin mixture containing certain other ingredients) marks a distinct advance over earlier methods of treatment, for the number of required injections of epinephrine is thus sharply reduced and striking clinical improvement frequently results. In some cases, intravenous injection of aminophyllin (in physiological salt solution) has given dramatic results; its use in so-called intractable asthma may reduce the number of cases in which more extreme measures are needed.

In intractable cases that do not respond to epinephrine or aminophyllin treatment, the rapid production of general anesthesia to a reasonably deep surgical level by means of ether and oil by rectum, or by the administration of cyclopropane, though not devoid of danger, has been recommended.

Still more advantageous in the treatment of intractable asthma and especially of the status asthmaticus is the inhalation of mixtures of helium and oxygen, particularly if the B. L. B. mask be used. At first the mixture to be inhaled consists of 80 per cent helium and 20 per cent oxygen; after relief of the spasm the amount of oxygen is relatively increased and when recovery from the attack is nearly complete, pure oxygen is inhaled. After the cycle of severe attacks has been interrupted by helium-oxygen treatment, the patient in later milder attacks even though previously 'epinephrine-fast' may be relieved again by that drug.

Intracutaneous tests with type-specific pneumococcus polysaccharides are now being used as a guide in the serum treatment of pneumococcal pneumonias. Theoretically this test would appear to be as soundly based as the Shick test that is used to measure skin resistance to diphtheria toxin. In the polysaccharide test a positive reaction indicates resistance to the pneumococcus, whereas in the Shick test a positive reaction indicates lack of resistance to diphtheria toxin. In both cases the skin reaction is used as a criterion of the immune status.

Sulfapyridine treatment is markedly reducing the mortality in pneumonia and is greatly shortening the course of the disease. Where it is possible, however, the causal pneumococcus should be typed and the corresponding anti-pneumococcus serum should be used in addition to the administration of sulfapyridine. These two therapeutic agents act synergistically and result in a lower rate of mortality than that experienced with either method of treatment alone.

It is possible that the ultra-centrifuge recently invented will prove to be useful in the concentration of the anti-bodies of immune sera, since through its use protein molecules of different sizes can be assorted, weighed, and purified. This same instrument may prove to be useful also in the study of pathogenic ultra-microscopic viruses.

An epidemic of 86 cases of this acute febrile respiratory infection recently (1939) occurred among students in Ithaca. It differs from ordinary pneumonia, since there are no large areas of true consolidation and it is not due to the pneumococcus. On X-ray examination, certain fan-shaped areas of increased density in the lung seem to be typical. The disease is probably identical with epidemics that occurred in Hawaii (1931-34), in Texas in 1935, and in Philadelphia in 1938. The disease is probably caused by a filtrable virus.

Examinations of workers, (carders, weavers, spinners, twisters, pickers) in the asbestos textile industry in North Carolina have revealed that the principal physical defect among them is infiltration of the lungs with asbestos particles. On X-ray examination of the chest, granular or 'ground-glass' markings are seen especially in the middle and lower parts of the lungs. The patients complain of cough, increasing pains in the chest, blood-streaked sputum, weakness and loss of weight. In the sputum the so-called 'asbestos bodies' can be seen on microscopic examination. The disease can be prevented by installation of exhaust ventilation near the source of dust, since if the concentration of asbestos dust in the air be kept below five million particles per cubic foot, new cases will not appear.

In the tri-state convergence of Kansas, Oklahoma, and Missouri, on the Ozark borders, is a large area of zinc and lead flat-lands with about 90,000 inhabitants, about half of whom are miners. Among the workmen, pulmonary silicosis is very common. This in time may be disabling in itself, or pulmonary tuberculosis may be super-imposed upon the silicosis. Better means of ventilation of the mines and the installation of blow fans and exhaust fans or other methods will doubtless be resorted to as preventive measures. (See also CHEMISTRY.)

The use of this test, though it began in Galen's time, has been recently growing very rapidly and is now regarded as of definite value in proving or disproving the existence of toxemia or of cellular destruction, in verifying the progress of improvement of patients and in the recognition of complicating processes. The test is not specific for any particular disease and the mechanism underlying it is obscure. Any marked increase in the erythrocyte sedimentation rate, except in pregnancy, strongly indicates a toxemia of one sort or another. The rate is accelerated in many acute and chronic illnesses, especially in diseases like pneumonia, tuberculosis, rheumatic fever, infectious arthritis and malignancy (accompanied by death of cells in the tumor). As a rule the rate is not increased in acute uncomplicated appendicitis not in simple hypertrophic arthritis. When in the course of an infectious disease (like pneumonia or acute rheumatic fever), one meets with a sharp rise in index, complications should be suspected and looked for.

Blood for purposes of transfusion can now be preserved and transported. Larger hospitals and other health services are, in many places, establishing 'blood banks' where blood of different types drawn from the arms of healthy persons may be kept in refrigerators and made immediately available. Placental blood, (advantageous because devoid of allergens) can well be salvaged and safely kept for at least 30 days.

Blood transfusion organizations and the establishment of large scale Government-controlled blood banks are now parts of the laboratory service of every army. In November 1939 Great Britain called upon a large number of young persons to volunteer blood for use among wounded soldiers.

Blood plasma is said to be superior to whole blood for intravenous injection in case of shock. Dried plasma, prepared by dehydration in vacuo when frozen, may be used as a source of supply, as, when redissolved and diluted, it retains its beneficial qualities.

The American Red Cross also keeps a registry of healthy volunteer donors whose bloods have been typed. Most persons belong to either the A or the O group; persons belonging to the B group are less common (1 in 6) and those belonging to the AB group are rare (1 to 6). When a donor belonging to any one of these groups is needed he or she can be promptly supplied from the central registry.

Anemia somewhat resembling pernicious anemia has been found in a number of such cases and is apparently due to stagnation and putrefaction of the intestinal contents. Success in therapy has followed intensive treatment with liver extract and surgical removal of the cause of the intestinal stagnation.

For some time, studies have been made of the renal pressor substance known as 'renin.' Potent extracts can now be prepared in experimental laboratories.

The anticoagulant 'heparin,' which has been isolated from liver and other tissues, has been found to act not on fibrinogen but on the thrombin system. It can now be obtained in pure form and stored as a dry powder to be dissolved when required for use. It may be given intravenously with safety to human beings over days or weeks. In cases in which statistics show that the incidence of postoperative thrombosis or embolism is relatively high it promises to be of value in prevention of thrombosis.

Heparin is also being used as an anticoagulant in giving blood transfusions, either in vitro to heparinize the drawn blood from the donor, or in vivo to heparinize the donor by intravenous injection.

Certain patients, usually past middle life, suffer from attacks of excruciating burning or boring pain, limited to one side of the head, from two to twenty times each week. These attacks come and go very quickly. There is dilatation of the blood vessels during the attacks on the side of the head affected. In persons suffering from this malady attacks can be induced by subcutaneous injection of histamine and these induced attacks as well as attacks occurring spontaneously can be controlled by intravenous administration of epinephrine and other vasoconstricting agents. It is especially interesting that long and perhaps permanent relief can be obtained in the majority of the patients by a series of small subcutaneous injections of histamine — the same substance that in larger doses will induce the attacks of pain.

The causes of peptic ulcer (gastric or duodenal) have been much discussed and various theories (inflammatory, infectious, vascular, traumatic, endocrine, allergic, neurogenic) have been promulgated. Though doubtless in many cases we have to deal with the interaction of several causal factors, the opinion is growing that in most cases, an abnormal nervous or mental state is the main cause. Through abnormal activity of the autonomic nervous system, disturbances of secretion and of motility of the gastrointestinal tract develop, that are conducive to the origin and increase in size of ulcer.

Formerly, in the treatment of peptic ulcer, surgical intervention was early resorted to. Today surgery is avoided in uncomplicated cases, though it may be imperative in cases of stenosis, perforation, massive or recurrent hemorrhage or malignancy. Medical treatment by bland diet (devoid of chemical, mechanical and thermal irritants at frequent intervals and of sufficient protein, caloric, mineral and vitamin content), by the use of colloidal aluminium hydroxide solution orally or by the continuous drip method, and by psychotherapy directed toward improvement of the emotional state and to corrections in the psychosexual sphere, is now in favor.

This disease appears to be due to a filtrable virus resembling the virus of pleuro-pneumonia. The virus has been isolated from human rheumatic exudates and grown on culture media; proof of its pathogenicity for laboratory animals has been brought. There is some discussion of the possibility that this virus may represent a filtrable phase of a streptococcus.

An epidemic of this disease (later called erythema arthriticum epidemicum) occurring at Haverhill, Mass., was described in 1926. An organism called Haverhillia multiformis has been pictured as the infectious agent. In sporadic cases of rat-bite fever, similar symptoms occur and a bacterium of closely related, if not the identical strain, is present in the blood. This form of rat-bite fever is, however, different from Japanese rat-bite fever (sodoku) in which there is no arthritis and which is caused by an organism called Spirillum minus. Arsenic acts as a specific in sodoku but not in Haverhill fever.

Good therapeutic results are being obtained in some cases from treatment of the affected joints with mecholyl (acetyl-betamethylcholine chloride) by iontophoresis. The joint is wrapped in gauze or asbestos fabric saturated with a weak solution of mecholyl; metal strips (not touching the skin anywhere) are then spirally wrapped around, the positive pole electrode is applied to the distal end of the metal strip and the negative pole electrode to some other portion of the body, and the patient is given a galvanic current of 15 to 25 milliamperes for 15 to 25 minutes or longer. The strength of the current is increased very gradually when it is turned on and decreased gradually when turned off. The treatment causes local vaso-dilatation and the treated part becomes warmer. After two or three treatments of a swollen and painful joint in rheumatoid arthritis the symptoms begin to be ameliorated. If diarrhoea occur, atropine is given. The method (in association of course with other forms of treatment) seems to be more efficacious in so-called rheumatoid arthritis than in hypertrophic osteoarthropathy.

It is interesting that this treatment has also proved to be efficacious for chronic varicose ulcer, and to some extent also for diabetic gangrene and for Buerger's disease (thromboangiitis obliterans).

Mecholyl treatment is best avoided in patients who have bronchial asthma or disease of the coronary arteries, or if used in them should be applied very cautiously.

Treatment of active chronic infectious arthritis in which the blood sedimentation rate is raised with various preparations of gold is gaining some supporters in this country and in Europe. It seems to be of no value in other forms of arthritis or in 'burned out' inactive chronic infectious arthritis. It should not be used in patients who in addition to their arthritis are pregnant or suffer from anemia, nephritis, hepatitis, or ulcerative colitis. Toxic reactions (dermatitis, hepatitis, aplastic anemia, agranulocytosis) are said to be rare if suitable dosage be used. The best results have been obtained in early cases of proliferative arthritis before severe crippling has developed.

This new remedy, which is a stimulant to the nervous system (central and sympathetic), has been found to be effective in the treatment of narcolepsy, to be of some help in the amelioration of the symptoms of post-encephalitic Parkinsonism, and, when inhaled, to relieve nasal congestion. It has also been used in states of depression of recent onset due to drugs (alcohol, barbiturates). Reports upon its value in the treatment of psychoses and psychoneuroses are conflicting. It is a toxic substance and should never be used except under medical supervision and then most cautiously.

Hospital physicians report an alarming increase in admissions of patients found to be suffering from bromide intoxications. Often before admission the relation of bromides to the symptoms has not been suspected. The use of bromides, formerly common in the treatment of epilepsy, is now common for the relief of headaches, nervousness and insomnia. They are often prescribed by physicians but many laymen purchase bromides for self-medication. Bromo-seltzer and bromidia and other advertised products contain bromides and are not infrequently responsible for bromide poisoning in persons who use them in large quantities.

In severe intoxication, the patients have disturbances of speech and memory and often become outspokenly delirious. The diagnosis is easy, if the intoxication is suspected, by determination of the bromine content of the blood. The treatment consists of withdrawal of all bromides and giving large quantities of common salt; in a few weeks the bromine can thus be removed from the blood and tissues.

It has been estimated that over two million doses of barbiturates are taken daily by the people of the United States. When used under proper medical supervision these drugs serve very useful purposes. But the promiscuous use of barbiturates is attended by many evils. Several hundred suicides yearly are due to barbiturates and the rate is showing an upward trend. Other evils include (1) habit formation, (2) cumulative toxic action, and (3) recognized causal factors in traffic accidents and in some criminal assaults.

The intramuscular injection of cobra venom is now being used for the relief of severe pains not yielding to ordinary analgesic treatments. Thus far it has found its greatest application in the treatment of intractable pains due to the late stages of cancer and in the lightning pains of locomotor ataxia. It would seem to be worthy of further trial, as in many instances through its use addiction to morphine may be avoided. When it fails, subdural injections of alcohol or the operation of chordotomy (cutting of the pain-conduction paths in the spinal cord) may become necessary. In some cases, injections of large amounts of vitamin B. have been found useful for the relief of severe pains.

Recently, the use of this method has attained to some favor for localizing diagnosis in diseases of the brain. Thus far its main clinical value lies (1) in the study of epilepsy and (2) in the localization of tumors that involve the cortex of the brain. On further investigation it may be found to be of practical value in the diagnostic study of other organic diseases of the brain and of certain mental disorders.

On account of its greater efficacy and the avoidance of the dangers of bromide intoxication, phenobarbital has largely displaced the bromides in the treatment of idiopathic epilepsy. Recently a remedy known as 'dilantin' (sodium diphenyl hydantoinate) has been recommended as being more effective and less dangerous than phenobarbital as an anticonvulsant.

The severe periodic one-sided headaches, lasting from several hours to half a day, known as 'migraine,' 'heimcrania,' or 'sick headache,' are a cause of much suffering in many persons. Physicians have been accustomed to relieve them by prescribing aspirin, amidopyrine and codeine, phenobarbital, or phenacetin and theobromine salicylate. Patients often resort to self-medication by advertised 'headache powders' or 'anti-headache solutions' containing acetanilide, bromides and other drugs. Gynergen (ergotamin tartrate), too, has been much employed as a remedy and in many cases has given quick relief. Caution cannot be over-emphasized, as over-use of these drugs without a physician's sanction is decidedly dangerous.

Recently, the breathing of pure oxygen, using the B.B.L. inhaler, at the onset of an attack of migraine, has been found to yield relief.

The use of metrazol to produce convulsions and the use of insulin to produce coma in the treatment of dementia praecox and other psychoses has been further studied during the past year and the technique of each procedure has been fully discussed. Since during the convulsions produced by metrazol, single or multiple fractures of the thoracic spine occur with considerable frequency despite the precautions now used to prevent sudden flexions of the spine, the tendency at present seems to be against metrazol and in favor of insulin.

The death this year of the founder of the psychoanalytic movement, Sigmund Freud, has been followed by lively discussions of his actual contributions to psychology, to psychiatry, and to general culture. Though his critics assert that he was not truly scientific in his mode of thought, was willing to accept mere speculation as incontrovertible truth, was wrong in his idea that human nature is unchangeable and made many errors concerning primitive man and society and the evolution of culture, it cannot be denied that he and other members of the psychoanalytic school (e.g., Jung, Ferenczi, Adler, Jones, Rank, Stekel, Alexander, Brill, Jelliffe, and Jaensch) whose opinions diverged from those of Freud have exerted a profound influence upon modern psychological conceptions and discussions. The amount of medical literature bearing upon the so-called 'unconscious,' the interpretation of dreams, infantile sexuality, the libido theory, the Oedipus complex, narcissism, the 'id,' transference, ambivalence, regressions, repressions, projections, and introversions, is enormous and has gone far toward expanding the vocabulary of those who study patients suffering from nervous and mental diseases. There are many sincere, hard-working and well-trained psychoanalysts but unfortunately many have been drawn into the psychoanalytic fold who lack general medical as well as sound psychiatric training. Medicine should be grateful for the extension of methods and of ideas in psychiatry but should also be cautious in evaluating claims especially of therapeutic results. Orthodox psychobiology and scientific psychiatry will make use of what is good and weed out what is ill in psychoanalytic theory and practice.

So-called 'ideal weight' of adults is estimated by allowing 110 pounds for 5 feet and adding 5½ pounds for each additional inch of height. Anyone weighing more than ten pounds more or ten pounds less is overnourished or undernourished, respectively.

In many general 'run-down' conditions, and especially in functional nervous disorders, the patients may be from 20 to 60 pounds under weight. In such cases, rapid gain in weight can often be quickly ensured by keeping the patients in bed ('rest cure'), injecting protein-zinc-insulin a half hour before breakfast and a half hour before the evening meal, and encouraging the patient to ingest a well-balanced diet of high caloric value. It is not uncommon to see patients gain regularly from 4 to 6 pounds weekly on this regimen. (See also BIOLOGICAL CHEMISTRY.)

Since patients with Addison's disease (adrenal insufficiency) began to be treated with potent extracts of adrenal cortex nine years ago, difficulties were for a time encountered in preparing the extract in large quantities and in the standardization of the hormone. Though the methods of preparation were improved in subsequent years, it was not until the so-called desoxy-corticosterone acetate (percorten) was prepared as a crystalline product that the treatment could be satisfactorily applied. Daily subcutaneous or intramuscular injections of the substance in sesame oil and the administration of several grams of sodium chloride daily are given until the blood-pressure has risen, the sodium and chloride balances are restored, the plasma volume has returned to normal and the plasma electrolytes are found to be in normal concentration. As soon as the daily maintenance dose has been determined, the injections are discontinued and under local anaesthesia one or more pellets of crystalline desoxy-corticosterone acetate may be implanted under the skin. By such implantation, further daily injections of the hormone become unnecessary and a great economy in the use of the hormone is effected. The outlook for patients suffering from Addison's disease is now better than ever before.

Recently, the method of subcutaneous implantation (after local nupercaine anaesthesia) of compressed crystals or pellets of pure testosterone of large size has been perfected with gratifying clinical results in the treatment of eunochoid patients (true testicular deficiency) with infantile sex organs and immaturity of sexual development. The value of this method of application must await further appraisement.

Difficulty of urination, because of beginning enlargement of the prostate is relieved in some persons by injections of testosterone propionate.

Symptoms at the time of or after the menopause in women can often be relieved by injections of testosterone propionate. Post-menopausal mental depressions can also often be ameliorated by the same method.

Unfortunately the high cost of testosterone propionate has up to now been a deterrent to its use. A new method of synthesis of the hormone has recently been worked out and may bring the price down.

In India, a new male hormone, artosterone, has been isolated from the East Indian Summer fruit. It is said to be of high potency and to yield results that compare favorably with other hormones that possess high androgenic activity.

This vitamin, abundant in citrus fruits and tomatoes, is also present in large quantities in fresh cantaloupe. Other good sources are broccoli, cauliflower and kale.

This anti-hemorrhagic vitamin that helps prevent internal hemorrhages in persons whose blood does not clot normally in that it helps to form prothrombin was derived from extracts of alfalfa but was obtained at first only in impure form (including K₁ and K₂). Later, the pure vitamin K was isolated in the form of a yellow oil. But vitamin K₁ has been found to have four times the potency of natural vitamin K. K₁ has been found to be a complex naphthoquinone derivative and recently it has been synthesized almost simultaneously in four different laboratories though the same chemical had been made synthetically as early as 1922 when no one knew of its relation to vitamins. Several pounds of pure K₁ are already available and this pure vitamin K₁ is now inexpensive. One milligram a day meets the needs of an adult, and half a milligram a day those of a babe.

A simple bedside thromboplastin test can now be used to determine whether or not a person suffers from vitamin K deficiency before an operation.

Birth injuries are often followed by slow oozing of blood into the brain or skull cavity; such hemorrhages may either be fatal or be followed by paralyses. The blood of infants is low in prothrombin content. These hemorrhages can probably be avoided by oral administration of vitamin K to the new born infant, or, better still, by giving the expectant mother vitamin K for several weeks prior to delivery. (See also Vitamins in section below.)

See INDIANS, AMERICAN: Health.

The proposed Wagner Act for the development of a National Health Program to be conducted by the Federal Government contains many provisions that are not acceptable to the American Medical Association of which the majority of licensed physicians are members. This association itself advocates a plan that it believes should be followed in the development of health activities and medical care for the people of the United States. In its platform the Association advocates: — (1) the establishment of an agency of the Federal government under which all medical and health functions of the Federal government, except those of the Army and Navy, shall be coordinated and administered, since at present these functions are divided among a multiplicity of departments, bureaus, and other Federal agencies; (2) the allotment of such funds as the Congress may make available to any state in actual need for the prevention of disease, the promotion of health and the care of the sick on proof of such need; (3) the principle that the care of the public health and the provision of medical service to the sick is primarily a local responsibility; (4) the development of a mechanism for meeting the needs of expansion of preventive medical services with local determination of needs and local control of administration; (5) the extension of medical care for the indigent and the medically indigent with local determination of needs and local control of administration; (6) that in the extension of medical services to all the people, the qualified medical and hospital facilities already established be utilized to the utmost; (7) the continued development of the private practice of medicine subject to any changes that may become necessary to maintain the quality of the services and to increase their availability; and (8) expansion of public health and medical services in a manner consistent with the American system of democracy with avoidance of plans that tend toward any system of totalitarianism or toward infringements upon essential liberty or abandonment of self-reliance, free-will and personal responsibility.

See ROCKEFELLER FOUNDATION.

No more revealing exposition of the trend of current research in bacteriology and its allied fields can be found than a cross section through several hundred papers read before the Third International Congress for Microbiology which was held in New York City from Sept. 2 to 9, 1939. Presenting the annual scientific harvest of the entire civilized world in nine different sections, this Congress covered the following general spheres of interest: Variation and taxonomy; bacterial growth and bacterial metabolism; nature and characteristics of filterable viruses, including bacteriophage; the immunology, pathology and epidemiology of certain virus diseases of man, animals and plants; the rickettsial diseases; immunity and resistance in protozoan and helminth infections; classification, genetics and host-parasite relationships in fungus diseases; the bacteriology of brucellosis, tuberculosis, salmonella infections, diphtheria, streptococcus diseases, anaerobic infections, spirochetoses, plague and tularemia, chemotherapy of bacterial infections; soil-food-water-sewage bacteriology; and, finally, various aspects of immunology, particularly allergy, clinical and immunological properties of bacterial antigens, nature of antibodies and the mechanism of antigen-antibody reactions.

No strikingly new discoveries were recorded during the past year. However experimental work has progressed on all fronts, resulting in a consolidation of older observations and a sharper crystallization of fundamental concepts. Such progress has been particularly marked in the following fields which will be discussed in greater detail:

(1) Physiological chemistry of bacterial metabolism.

(2) Methods and results of virus cultivation.

(3) New evidence of intermediary vectors in virus diseases.

(4) Epidemiological and susceptibility problems in poliomyelitis.

(5) Rabies vaccination.

(6) Studies of the pleuropneumonia-like group of organisms.

(7) The rheumatic fever problem.

(8) Chemotherapy of infectious diseases by substances of the sulfonamide type.

(9) Mechanism of antigen-antibody reactions.

(10) Nonspecific factors in resistance to infectious diseases.

Knowledge of the growth requirements of microorganisms has been further developed to a point that synthetic media, consisting chiefly of amino acids and certain accessory factors, can now be used for the successful cultivation of several bacteria. A medium devised by Mueller for the diphtheria bacillus, for instance, contains the following ingredients: acid hydrolysate of casein, β-alanine, nicotinic acid, pimelic acid, cysteine, maltose and inorganic salts, an optimum iron content controlling the yield of toxin. Further studies by Mueller and by Evans and his associates showed that C. diphtheriae, grown in synthetic media with three of these substances (β-alanine, nicotinic acid, pimelic acid), is able to synthesize pantothenic acid; compounds similar to aneurin, co-enzymes I or II, and riboflavin are also synthesized. Hemolytic streptococci were shown by Woolley and Hutchings to require riboflavin, pantothenic acid and a suitable reducing compound, reduced iron appearing most effective. The necessity for the presence of pantothenic acid was confirmed by Subarrow and Ranc. The inability of this organism to reform the amide linkage when the split products of pantothenic acid are available is comparable to the limited ability of the streptococcus to form the amide linkage of glutamine from glutamic acid (Mcllwain, Fildes, Gladstone and Knight). Somewhat analogous is the case of the dysentery bacillus which according to Kligler needs nicotinic acid to ferment glucose. The great influence of nicotinamide on the respiration of this organism was also emphasized by Dorfman et al.

Amplifying his earlier work on bacterial enzymes, Dubos has prepared an extract from a soil bacillus which is capable of attacking and killing certain pathogenic Gram-positive microorganisms. The purified principle was of such potency that as little as 0.01 to 0.1 mg. of the heat stable protein-free substance was sufficient to kill in vitro the following bacteria: Diplococcus pneumoniac, Streptococcus hemolyticus groups A, C, and D, Streptococcus viridans, and Staphylococcus aurcus. Inhibition of the glucose dehydrogenase preceded lysis of all susceptible microorganisms, except the streptococci. Since the organisms in this group were equally affected, regardless of type or culture phase, it was suggested that the 'effect of the bactericidal agent is directed against a cellular structure or function which is common to all these bacterial species.' The same material was found to be without any effect on Gram-negative organisms, such as E. coli, Hem. influenzae, Kl. pneumoniae, etc. Experiments with mice demonstrated both a protective and a curative action against Pneumococci Types I, II, III, V, VIII.

Following the discovery of the so-called blood group enzymes of animal origin, a few species of bacteria were found which are also capable of decomposing the blood group specific substance A. Schiff has now reported on the preparation of such a group-specific, highly unstable ectoenzyme, not connected with any hemotoxin, from cultures of C. welchii, which was obtained by filtration of anaerobically grown cultures.

In the realm of virus cultivation, substantial progress has been made with the lymphogranuloma virus by Gey and Bang, as well as by Sanders. Using cells from a pure strain of tumor fibroblasts in a fluid medium of balanced salt solution, bovine extract, chicken plasma, and human placental cord serum, the first mentioned authors succeeded in keeping the virus alive for 53 days. Sanders, who worked with preparations containing embryonic guinea-pig brain and ultrafiltrate of ox serum, demonstrated increased potencies of 1,000 times judging from consistent results obtained with animal inoculations and skin tests. The same author has also presented a critical review of 37 filterable virus with respect to methods of cultivation, involving both tissue cultures as well as chorioallantoic preparations.

Zinsser and his associates have described in detail perfection of a cultivation method which permits the maintenance of rickettsia on agar-tissue cultures. Formalinized or phenol-killed organisms obtained from such media have functioned as efficient vaccines in protecting guinea pigs against infection with highly virulent passage virus. Another approach to the same problem was taken by Cox who published a new technique utilizing the yolk sac of the developing chick embryo for the cultivation of rickettsia. With this method several strains of rickettsia, including the classical typhus fever organisms and those which produce Rocky Mountain spotted fever, were readily maintained in serial passage. The infectivity of such cultures, as a rule, was 100 to 1,000 times greater than had previously been obtained with other media, approaching the limits reported for tick tissues. In a later paper the same author describes the preparation of a vaccine made from infected embryonic tissues of developing chicks (pooled yolk sac, chorioallantois and embryo) which proved a potent immunizing and protecting agent in guinea pigs.

Stimulated by the experimental demonstration that insect vectors can transmit in laboratory animals certain neurotropic virus diseases, such as equine encephalomyelitis (several varieties of Aëdes mosquitoes) and Japanese B encephalitis (Culex pipiens, Culex tritaeniohynchus), renewed efforts were made to link the extremely spotty distribution of cases of St. Louis encephalitis, lymphocytic choriomeningitis, and of poliomyelitis with transmission by biting insects. Thus, Howitt discusses recent epidemiological evidence to show that Culex pipiens might have been implicated during the St. Louis outbreak of encephalitis. Shaughnessy and Milzer report experimental infection of all stages in the life cycle of Dermacentor andersoni with the virus of lymphocytic choriomeningitis. The disease was also transmitted by applying infected crushed ticks or feces from infected ticks to the scarified skin of guinea pigs. The possibility of an external reservoir of the virus of lymphocytic choriomeningitis in rodents, whence it may be conveyed to man by infected insects or arthropods, appears more likely from recent work of Armstrong's. This author succeeded in isolating the virus from gray mice (Mus. muscularis) which were trapped in houses where proved human cases of the disease had occurred. In contrast to the two mentioned diseases, renewed attempts to transmit poliomyelitis to monkeys through supposedly infected mosquitoes (Aëdes acgypti, Culex pipiens) produced clearly negative results in the hands of Cornell and Davis.

The marked concentration of human cases of encephalitis in areas where equine encephalomyelitis was prevalent and the isolation of an Eastern strain of this virus from both man and horse had given rise to speculation whether the disease may not be carried by insects from animal to man. Proof of the human pathogenicity of the virus of equine encephalomyelitis by Fothergill, Holden and Wyckoff strengthens this assumption. A laboratory technician who had worked with the Western strain of this virus developed encephalomyelitis and died. A virus was isolated from the spinal fluid and brain taken at autopsy, which proved to be identical with the Western strain of equine encephalomyelitis virus as determined by specific neutralization tests. Similar evidence of indirect nature was adduced by Olitsky and Morgan. A laboratory worker who had been handling the Eastern strain of the virus became acutely ill with symptoms of encephalitis and subsequently recovered. The patient's serum, obtained five weeks after the onset of the disease, had specific virucidal properties against the Eastern strain of equine encephalomyelitis. Data are also mentioned suggesting that the disease may occur in a clinically inapparent form which is accompanied by specific antibody production.

New contributions of possible significance for the epidemiology of human influenza were made by Shope suggesting a highly complex mechanism in the mode of transmission of the swine influenza virus. The ova of swine lungworms, passed with the animal's feces, are swallowed by earthworms in which they are hatched as larvae; these larvae, when ingested again with earthworms by pigs, develop into adult worms which eventually reach the respiratory tract of the animal. It appears that lungworm larvae from pigs with swine influenza may harbor the virus throughout their development, both in their intermediary host, the earthworm, and in their definite host, the swine. The virus apparently lies latent within the lungworm after the parasite has reached the swine respiratory tract and causes infection only when a provocative stimulus is applied.

Studies in poliomyelitis have figured prominently during the past year, with little agreement of opinion among individual observers. These studies have proceeded along two main lines of approach, i.e., efforts made to elucidate the mode of transmission of the virus, and attempts undertaken to analyze the factors that determine individual predisposition of the disease. A majority of workers, on the basis of experimental data, still favor transmission through droplet infection along the nasal pathway (King), even though present methods of chemical blockade of the olfactory area are now recognized to have distinct practical limitations as possible prophylactic measures in man (Schultz). On the other hand, increasing evidence has lately accumulated to show that the virus may be present not only in the stools of cases or contacts (Kramer, Lepine et al.), but also in outside reservoirs, such as well water (Kling) and sewage (Paul and Trask). These facts, taken together, serve to raise anew the debatable question whether the gastrointestinal tract may not, after all, serve as a portal of entry as well as a channel of egress for the infectious agent.

Study of the special constitutional qualities of persons susceptible to infantile paralysis appears to attract an ever widening circle of investigators. Thus, one entire chapter in the new monograph on Poliomyelitis, by Kleinschmidt, is given over to a discussion of various endogenous factors, i.e., constitutional types, hereditary characteristics and blood group patterns, in cases of the disease. Similarly, Draper and Dupertuis have added new significant data to their earlier observations which indicate that susceptible individuals exhibit a genetically conditioned syndrome of definite morphological features which include certain anthropometric deviations in the measurements of the eye and its structures, teeth deformities and abnormalities in pigmentation of the skin. The sum total of these stigmata is interpreted as evidencing a lack of coordination between growth and development, making it appear as though there were a splitting of the two forces which carry the organism to completion. The concept of constitutional dysfunction is also reflected in the continued studies of Aycock, Toomey, and Jungeblut. Aycock, who has stressed for years the significance of endocrine unbalance, comes to the conclusion that some disturbance in the economy of estrogenic substance, which regulates the permeability of mucous membranes, is involved in susceptibility to paralytic poliomyelitis. These conclusions are based partly on estrogen assay of the urine of poliomyelitic patients, partly on the inhibition of nasal infection in monkeys prepared by previous treatment with this substance. Toomey finds that peripheral nerve fibers from rachitic monkeys, fed a diet deficient in vitamin D, absorbed the virus more easily than nerve fibers from normal animals; hence the supposition that deficiency in the healthy myelin sheath may open the way for conduction of the virus from the periphery to the central nervous system. Jungeblut's work is based on the demonstration that ascorbic acid inactivates the virus in vitro and that administration of the same substance tends to lessen the severity of the experimental infection in monkeys. The inference was therefore made that normally balanced vitamin C metabolism may be one of the factors concerned with successful operation of the mechanism of natural resistance. A survey of the clinical and epidemiological facts, known to precipitate the disease in epidemic form, suggests that they can be fitted into a system of predisposing factors in which faulty vitamin C metabolism, expressed by tissue saturation and peripheral excretion, is the common denominator. Clinical observations by Heaslip during a recent outbreak of poliomyelitis in South Australia are in agreement with this viewpoint. By measuring the rate of urinary excretion of ascorbic acid under a load test a C deficiency was demonstrated in patients but not in healthy contacts. The long suspected correlation between susceptibility to poliomyelitis and to diphtheria (Jungeblut, Fischer and Stillerman, Foley) — conceivably referable to a common vitamin C deficiency — finds further support in recent epidemiological observations from Australia (Dwyer) and in experimental data published by Burnet and his associates. Another attempt to correlate conditions suitable for virus multiplication with peculiarities of cell metabolism was made by Howe and Bodian. According to these authors, highly susceptible nerve cells in the olfactory bulbs and in the anterior horns of the spinal cord of rhesus monkeys may be rendered resistant to subsequent invasion of poliomyelitic virus by previous sectioning of the peripheral neuron. The morphological changes ('axone reaction' or 'chromatolysis') which ensue upon sectioning of the nerve in the corresponding ganglion cells are believed to express a state of increased metabolic activity of the nerve cell itself.

The possibility that animals other than apes and Old World monkeys may be susceptible to the virus of poliomyelitis has come up again in two recent publications. Frauchiger, in Switzerland, describes the occurrence of a paralytic disease in cattle, with nervous lesions resembling poliomyelitis, on farms where human cases of infantile paralysis had occurred. In the United States, Armstrong has reported apparent success in producing experimental poliomyelitis in the cotton rat (Sigmodon hispidus littoralis) by inoculation with one human strain of the virus, but not with a highly virulent monkey-adapted passage strain of virus.

Considerable doubt is expressed by Webster's work that commercial antirabic vaccines containing nonvirulent virus will immunize animals effectively under experimental conditions unless the vaccine, in large and usually multiple doses, is administered prior to peripheral inoculation of the infections agent. Mouse potency tests for measuring quantitatively the prophylactic value of vaccines indicated that vaccines containing virulent virus induce protection in mice but that the margin between immunizing and infecting doses is small.

New findings of potential significance for systematic bacteriology were announced concerning the pleuropneumonia-like organisms. Dienes, and Dawson and Hobby offer evidence that the L1 organism may be a variant of the Streptobacillus moniliformis rather than a symbiont, as claimed by Kleineberger. To the series of minute, fragile pleomorphic microorganisms, designated by Kleineberger as 'L forms,' were added several new members, both of rat and mouse origin. The nature of the pyogenic filterable agent encountered in the white rat by Woglom and Warren was clarified by successful cultivation of the L4 organism from this material by Kleineberger, as well as by Woglom and Warren. Pure cultures of this form were found to be highly virulent in rats and mice.

In the course of experiments with toxoplasmosis of mice, Sabin uncovered a filterable neurolytic agent endowed with high affinity for the cerebellum. In a series of papers, he demonstrated the new agent to be a soluble exotoxin produced by a pleuropneumonia-like microorganism, which he designated as strain 'A'; a second similar but nontoxogenic strain was obtained from the brain of a normal mouse and was called strain 'B.' This strain is distinguished from all other known bacteria by its capacity to produce in mice a chronic arthritis of the proliferative type. According to a subsequent paper by the same author, such organisms may be frequent inhabitants of the nasal mucosa, brain and external surfaces of the eye, three serologically distinct but antigentically related strains having been isolated so far from these sources.

Simultaneously with Sabin's work in America, Findlay and his associates in England encountered a peculiar syndrome ('Rolling disease') in some of their mice used for the study of lymphocytic choriomeningitis. From the brains of infected mice a pleuropneumonia-like organism (L5) was isolated which proved to be closely related to, if not identical with, the strain 'A' of Sabin. The same authors described a 'spontaneous polyarthritis' of rats, which was shown to be caused by similar pleuropneumonia-like forms (L6, L7). Collier, however, found it impossible to cultivate from rats suffering from spontaneous polyarthritis any microorganism that might be considered to have etiological significance. Striking prophylactic effects of certain gold salts on L4, L5, L6, and L7 infections in rats and mice were noted by the English workers, and correlated by Kling et al. with a stimulation of the reticulo-endothelial system.

The reported isolation by Swift and Brown of pleuropneumonia-like forms from human rheumatic material was later retracted by the same authors.

Many workers have postulated that acute rheumatism is the result of direct invasion of the joint and cardiac tissues by streptococci, but an even greater number have recorded complete failure to recover organisms from any site in rheumatic subjects. In a series of nine cases of rheumatic carditis. Green has now succeeded in recovering, in eight instances, hemolytic streptococci from vegetations on the heart valves and from pericardial lesions. Such organisms could not be cultivated from valves without macroscopic lesions nor from heart blood in the same cases. In five cases, hemolytic streptococci were recovered from the throat during life and in each case the strain was serologically identical with that isolated from the cardiac lesions. The quoted results go a long way in adding direct proof to the postulated streptococcal etiology of rheumatic fever.

Interest in the chemotherapy of infectious diseases continues to center around experimental results and clinical applications obtainable with substances of the sulfonamide type in various bacterial and virus infections. The favorable experience gained during the preceding year with the sulfanilamide treatment of hemolytic streptococcus, meningococcus, and gonococcus infections — to mention merely the outstanding examples — is also reflected throughout clinical reports published during 1939 (Marshall). In tuberculosis, the usefulness of sulfanilamide is still debatable (Steinbach et al., Corper et al., Birkhaug). A claim by Crossley that a new derivative, N1 dodecanoylsulfanilamide, has produced beneficial effects in experimental tuberculosis remains as yet without confirmation.

Following its earlier pioneering use in certain virus diseases, such as distemper, lymphocytic choriomeningitis and lymphogranuloma inguinale, sulfanilamide has now been successfully applied to the therapy of trachoma, by Kirk et al., Heinermann, Harley et al., and by Richards, Foster and Thygeson. Healing or striking improvement was obtained in a high proportion of cases. Destruction of the virus was indicated by a disappearance of the epithelial cell inclusion bodies characteristic of active trachoma.

Undoubtedly the greatest medical advance in the field of chemotherapy is the introduction of sulfapyridine. Although only a short time has elapsed since Whitby, in England, first published his discovery, a large number of papers from various countries all attest to the remarkable efficacy of the new drug. As a result of extensive clinical trials during the past year it may now be taken as an established fact that sulfapyridine is the most effective agent against infection by pneumococci of all types, for it appears to be not only superior to specific antiserum, but is unapproached by any other chemotherapeutic compound, including its mother substance sulfanilamide. A summary by Marriott of a total of 1,991 carefully observed cases of lobar pneumonia, which were treated with sulfapyridine all over the world (Africa, Canada, Denmark, Finland, Great Britain, Norway, and the United States), shows an average mortality of 5.5 per cent. Also with pneumococcus meningitis, formerly considered to be invariably fatal, sulfapyridine seems to permit of a revision of the hopeless prognosis (Hodes et al.). The possibility that sulfapyridine may be of value in infections due to Hemophilus influenzae is held out by a report from Pittman who succeeded in protecting mice against experimental infection with the influenza bacillus by administration of the drug. Dangerous toxic effects from sulfapyridine in therapeutic doses have rarely been reported, though nausea and vomiting are at least as frequent and severe as with sulfanilamide.

The cyanosis characteristic of sulfanilamide therapy has been further studied with some suggestive data as to its cause. By the use of an objective recording spectrophotometer (Fox and Cline) and by an extensive combined chemical spectrophotometric survey (Harris and Michel), the presence of methemoglobinemia in vivo was conclusively demonstrated. Direct conversion of hemoglobin into methemoglobin through the action of a potent oxidant formed from sulfanilamide could also be proved by in vitro experiments of the above mentioned authors. Further investigations of the relation of this oxidation phenomenon to the mode of action of the drug should materially contribute to our knowledge of the chemotherapeutic mechanism itself (Fox).

In a comprehensive review, Heidelberger discusses the mechanism of immune reactions, involving especially specific precipitation and bacterial agglutination, in the light of newer data obtained by the application of quantitative absolute methods which conform to the criteria of analytical chemistry. The author concludes that the analytical methods have withstood all tests for accuracy and reliability even though the quantitative theory itself, in spite of its accepted utility, is still defective in certain respects.

A new and important application of physical chemistry to immunology is electrophoretic analysis of immune serum by the Tiselius moving boundary method, its principle depending upon the differential mobility of proteins in buffered solutions when a current is passed. While normal sera produced discrete bands, indicative of albumin, fibrinogen, and a, β, g globulins, immune sera were shown to produce either a band between β and g globulin or an increased g band. That this change is caused by the antibody was proved by the normal appearance of the same sera after absorption of the antibody by antigen. By using this method, Tiselius and Kabat measured the antibody content of various anti-sera and prepared antibody solutions of high purity.

A review by Webster of the significance of heredity in the infectious diseases summarizes the essential facts that have emerged from studies of experimental epidemiology, with particular reference to innately high or low susceptibility to such infections as mouse typhoid and St. Louis encephalitis. It appears that among the environmental agents which may modify the inherited factors, diet is the most important one, inasmuch as it has proved capable of changing susceptibles to resistants and vice versa. Indeed, epidemics may be started and terminated merely by altering the dietary régime.

Locke has published new data which suggest that at least one of the factors connected with nonspecific resistance to infection lies in the capacity to maintain improved circulation. The length of time required for rabbits to return to normal temperature levels following chilling was taken as an index of fitness. When animals affected by various procedures producing circulatory impairment were compared with normal animals in their ability to survive the injection of small doses of virulent Type I pneumococci, a direct relation was found to exist between the warming time and resistance to infection.

A growing appreciation of the rôle of vitamins, especially vitamin C, in conditioning susceptibility to and determining the course of certain infectious diseases is mirrored in a number of publications dealing with experimental or clinical observations. Apart from the significance of vitamin C for the problem of predisposition to poliomyelitis, which is discussed elsewhere in this review, such evidence has been strongest with diphtheria, tuberculosis, whooping cough, rheumatic fever, and possibly dental infections such as pyorrhea and Vincent's angina. Thus, Sigal adds new data concerning the development of scorbutic symptoms in chronic diphtheritic intoxication of guinea pigs and Kuendiger and Salus report marked C deficiencies in patients suffering from diphtheria. However, administration of ascorbic acid and cortin to cases of malignant diphtheria still falls short of producing therapeutic results with any degree of regularity (Engelbach, Mautner). In tuberculosis, both Steinbach and Birkhaug agree that the disease is accompanied by C hypovitaminosis and that vitamin therapy moderates the severity of the symptoms and lessens the toxicity of tuberculin shock. The treatment of whooping cough with vitamin C has been widely adopted by clinicians with favorable results as regards reduction in the number of paroxysms and in the duration of the disease (Editorial, N. Y. State Jour. Med., April 1939). The usefulness of C medication in rheumatic fever is still sub judice (Hall et al.); the specific relation of C deficiency to dental infections has not up to the present been clearly defined (Sandberg and Dagulf, Williams, Kirkpatrick, Topping and Fraser, Tomlinson).

As cancer is a growth composed of living cells which have an extraordinary capacity of growth in the body without causing any immediate reaction, an enormous amount of study has been carried on to see what minute chemical differences there might be between the composition of the cells of a malignant tumor and the cells of healthy tissues, obviously with the hope that some difference might be demonstrated which would enable one to attack the tumor cell and spare the healthy cell. No characteristic differences have been found hitherto and the chemical composition of the malignant cell and its ferments have been shown to be in general the same as those which occur in normal cells, perhaps in some instances differing slightly in their amounts. No abnormal mineral substances have been found in the cancer cells; they contain exactly the same quantities as exist in other cells. Usually cancer cells contain more water than normal cells, but that is a characteristic of all rapidly growing tissue. Some years ago Dr. Otto Warburg of Germany thought that he found in the sugar breakdown of the cancer cell a difference from that of the normal cell and that this difference might be a characteristic of cancer; but further investigation showed that this property was shared by many healthy cells, and the idea that a special type of glucose fermentation was characteristic of the cancer cell had to be abandoned.

Recently, however, Drs. Kogl and Erxleben of Holland published some interesting studies on the proteins of the cancer cell. They found that some of the amino-acids which form the skeleton of the protein molecule turn the plane of polarized light to the right instead of to the left as does the ordinary type of amino-acid in healthy tissues. Their analyses have shown that a considerable proportion of the amino-acids derived from the cancer cell protein may be of the type which rotates the plane of polarization to the right. This phenomenon, they think, may explain why the cancer cell is not destroyed in the body when a normal cell out of place would be; and they point out that many substances exist in nature which contain both the right-turning and left-turning capacity. In fact, it was the great Pasteur whose first fame was based upon his picking out by hand crystals of tartaric acid, some of which had a left-sided face and others a right-sided face, thus proving that ordinary tartaric acid, which does not rotate, can be divided into one which rotates to the right and another, to the left. It has long been known that some ferments act more readily on the left-rotating amino-acids of the proteins and that other forms will not act on the right-turning variety. Hence Kogl and his co-workers think that this may explain why the cancer cell enjoys a certain immunity. A number of investigators have challenged the correctness of Kogl's work and, therefore, of his theories, but so far he has successfully defended himself. It will take years of labor in laboratories throughout the world to decide this question. In the meantime reliance will have to be placed upon the standard methods for the treatment of cancer by surgery and radiation.

The scientific world never stands still and Drs. Temple Fay and Lawrence W. Smith of Philadelphia have brought out a new method of treating cancer, which consists of 'cooling' the patient. As a matter of fact, the patient goes to sleep just as a hibernating animal does in winter; and if the temperatures are carefully kept from going too low, the patient may live in that considerably lowered state of activity for days. When awakened, patients, who have no remembrance of what occurred, in some instances find their tumors shrunk and pain no longer present; they do not, then, have to have sedative drugs if these were necessary before the treatment was undertaken. The chilling of poorly nourished tissues is a dangerous thing, however, and some persons have died from the heart muscle's not continuing to beat when its circulation was reduced by cooling. It is impossible to say at present whether this method will prove in any way practically useful. For the time being, it must be regarded merely as an experiment to test how much the growth of a cancer can be slowed down by contracting its vessels and thus reducing the food supply, and by diminishing the general activity of the cells by lowering the temperature. For a final answer we may have to wait for years.

On Feb. 28, 1939, Senator Robert F. Wagner of New York introduced in the Senate of the United States a bill known as the 'National Health Act of 1939.' It was intended to carry into effect recommendations of the 'Interdepartmental Committee to Coordinate Health and Welfare Activities,' which presented a report to a National Health Conference meeting at Washington in July 1938, calling for a 10-year program at an ultimate cost of $850,000,000 per year at the end of that period. The Wagner Bill called for immediate appropriations of approximately $111,000,000 for the first year, and 'for each fiscal year thereafter a sum sufficient to carry out the purposes.'

The purposes of the bill are described in its preamble: 'To provide for the general welfare by enabling the several states to make more adequate provision for public health, prevention and control of disease, maternal and child health services, construction and maintenance of needed hospitals and health centers, care of the sick, disability insurance and training of personnel.'

The House of Delegates of the American Medical Association meeting in regular annual session May 18, at St. Louis, declared the bill to be 'contrary to the best interests of the American people.' Principal among 22 items cited as ground for opposition to the bill were: Its provision for supreme Federal control; no provision of method of determining nature and extent of local need; Federal subsidies would be used to promote the ideas of officers and employees of the national government; any state in actual need for the promotion of health and the care of the sick should be able to do so without stimulating every other state to seek and obtain similar aid, thus to have imposed on it the burden of Federal control; the bill insidiously promotes the development of a complete system of tax-supported governmental medical care, does not safeguard in any way the continued existence of the private practitioners who have always brought to the people the benefits of scientific research and treatment, and it does not provide for the use of thousands of beds now available in hundreds of church and community general hospitals. The House of Delegates urged 'the development of a mechanism for meeting the needs for expansion of preventive medical services, extension of medical care for the indigent and the medically indigent, with local determination of needs and local control of administration, within the philosophy of the American form of government and without damage to the quality of medical service.'

The Wagner National Health Act was referred to the Senate Committee on Education and Labor, which delegated to a sub-committee the duty of conducting hearings and reporting on the bill, known as 'S. 1620.' The sub-committee comprised Senators James E. Murray of Montana, chairman; Vic Donahey of Ohio, Allen J. Ellender of Louisiana, Robert M. La Follette, Jr., of Wisconsin. Hearings on the bill took place during April, May and June. Many witnesses of differing views were heard by the committee. These comprised officials of government and voluntary public health organizations; leaders of organized medical groups; representatives of organized labor, of farmers' organizations, and of social work institutions; educators, and a journalist who volunteered to make a plea for '50,000 drugless doctors,' whom he claimed were left out in the provisions of the bill. Senator Wagner, though not a member of the sub-committee, was a frequent visitor and was permitted to question witnesses.

The proceedings of the Committee have been published by the Government Printing Office in three volumes totaling 956 pages. From this alone the complexities of delineating a National Health Program are apparent. A perusal of these proceedings discloses that in a number of particulars the sub-committee evinced a disposition to amend the bill, and it is expected that early in the session of the 77th Congress in 1940 a favorable report, containing recommendations for amendment, will be rendered to the Senate.

On Nov. 17 the Board of Trustees of the American Medical Association enunciated the gist of previous resolutions of its House of Delegates in the form of an 8-point program called the 'Platform of the American Medical Association':

1. The establishment of an agency of Federal Government under which shall be coordinated and administered all medical and health functions of the Federal Government exclusive of those of the Army and Navy.

2. The allotment of such funds as the Congress may make available to any state in actual need for the prevention of disease, the promotion of health, and the care of the sick on proof of such need.

3. The principle that the care of the public health and the provision of medical service to the sick is primarily a local responsibility.

4. The development of a mechanism for meeting the needs of expansion of preventive medical services with local determination of needs and local control of administration.

5. The extension of medical care for the indigent and medically indigent with local determination of needs and local control of administration.

6. In the extension of medical services to all the people, the utmost utilization of qualified medical and hospital facilities already established.

7. The continued development of the private practice of medicine, subject to such changes as may be necessary to maintain the quality of medical services and to increase their availability.

8. Expansion of public health and medical services consistent with the American system of democracy.

While attention was directed during 1939 to a National Health Program, the issue of compulsory health insurance was momentarily obscured. By indirection, though not by specific authorization, the Wagner Bill was permissive of grants-in-aid to states to institute local systems of compulsory health insurance, as a method of effecting one of its general provisions.

On Dec. 9, the American Association for Social Security announced that a new bill for compulsory health insurance had been drafted and would be introduced in state legislatures throughout the nation. As reported by Abraham Epstein, secretary of the association, and Herman A. Gray of New York University, chairman of the State Advisory Council on Unemployment Insurance, it would provide for tax contributions by employers, employees and the State, with coverage limited to persons earning less than $1500 or $2000 per year.

During 1939 further progress was made throughout the country, especially in New York, California, Michigan, Washington, Ohio, Pennsylvania, New Jersey and the District of Columbia, with plans sponsored by the organized medical profession for voluntary medical indemnity insurance. Under this system full freedom is allowed the individual to participate or not, as he wishes. Some of these plans have required amendment to insurance laws, as in the case of New York, where the Medical Society of the State of New York sponsored a new law during the session of the 1939 legislature, making it possible to institute non-profit associations of laymen and physicians to organize and operate the system. Authority to do business as insurers of physicians' fees, comparable to the 3-cents-a-day plan for hospital charges, was granted during 1939 under this new law to the following groups in New York State: Western New York Plan, Inc., Buffalo; Medical and Surgical Care, Inc., Utica; Medical Expense Fund of New York, Brooklyn. The chief objection to such plans has been the lack of actuarial information as to the extent of use and therefore the cost of operation. This is believed to have been obviated by a 'unit' system, under which participating doctors are credited with units instead of money for particular services performed, but payment in full on the earned fee schedule is deferred so that if costs of operation exceed income, payments will be made pro rata. Thus the physicians insure their own insurance from possible insolvency due to unexpected demands.

President Roosevelt, whose sponsorship of the activities of the Interdepartmental Committee to Coordinate Health and Welfare Activities did much to stimulate public discussion of the subject of a National Health Program, announced a proposal on Dec. 22 which implied temporary abandonment of legislation such as that represented in the Wagner Health Bill. He advocated Federal construction of hospitals and medical centers in poor states, and stated he would recommend such legislation to Congress. This he suggested for immediate action. The President was quoted in the responsible daily press as preferring such a measure at this time rather than wait for a complete and perfected plan for a national health program. He expressed the view that no hospitals should be built until an expert committee of doctors and public health officials were satisfied that a community could operate it successfully. The President was reported as saying that his hospital plan was not a substitute for the Wagner Health Bill, but was simply a first step that could be put through the coming session without waiting for a nation plan.

It is expected that organized medicine will approve legislation of this sort, if inspection of a specific bill shows that its provisions are in accord with the principles of 'local determination of needs and local control of administration,' and 'the utmost utilization of qualified medical and hospital facilities already established.'

Artificial pneumothorax has been used in the treatment of pulmonary tuberculosis for some years. In this method of treatment air or some other gas is permitted to be sucked into the potential space between the covering of the lung and the covering of the chest cavity, the two layers of pleura. When this happens the lung, which is an overdistended air-containing body, naturally retracts, becoming smaller and smaller as the quantity of air is increased and at the same time proportionately losing its breathing capacity. Thus the lung is temporarily put at rest and healing of the pulmonary tuberculosis more readily accomplished than if the lung continued to function or work. Likewise intrapulmonary cavities are better able to heal due to the retraction of the lung.

In a fairly large number of patients having pulmonary tuberculosis the two layers of pleura are bound together by adhesions, the result of a previous inflammation of the pleura, and as air cannot be introduced between the layers the artificial pneumothorax treatment fails. For many of these patients the method of putting the lung at rest has been by means of thoracoplasty. The operation consists of removal of portions of a few or more ribs, allowing the chest to fall in or retract in the areas so treated. Commonly this is known as the 'rib operation' and it, also, has been in use for some years. This operation causes varying degrees of shock to the patient and some patients not in physical condition to warrant such a risk at one time, may be sufficiently benefitted by other forms of treatment so that later they may be physically able to withstand the shock.

Recently another method of administering pneumothorax, not as shocking to the patient as a thoracoplasty and perhaps preparatory to thoracoplasty, has been offered such patients. This is known as 'extra-pleural pneumothorax' in contradistinction to the usual 'intrapleural pneumothorax.' When it can be performed, extrapleural pneumothorax causes less shock to the patient and permits marked collapse of the lung in the area treated. Layers of fascia, tissue, which normally occur between the chest wall pleura and the chest muscles and ribs, in this operation are separated by the operator's fingers, peeled off, so to speak, and the lung permitted to collapse by means of air filling the created space. Sometimes the layers of fascia stick together and are hard to separate. This operation is not always entirely free of complications and, unlike in intrapleural pneumothorax, the lung is not allowed to re-expand after a definite period of time has elapsed so the space, once established, must remain. Periodic air injections may be administered to maintain the created space or some form of fluid, such as oil, may be used. Because of the dangers of lung or cavity rupture, and because the space remains continuously, surgeons do not look upon the operation with favor except where necessary because of the patient's condition. When possible, a thoracoplasty is preferred by them. Nevertheless it is of distinct advantage at times and seems to be another step in the progress of treatment of pulmonary tuberculosis.

Most of the examinations used for the detection of human pulmonary tuberculosis have been routine for some time. The celluloid or paper films used are expensive, rather large, 14 x 17 inches, and much storage space is required if they are to be filed for future reference and comparison. Recently, at a very much lower cost, films have been made of the X-ray image on the fluoroscopic screen. The films are small in size, usually less than 4 x 5 inches, and may be taken on a single roll. For examination the pictures are easily magnified through proper enlarging lenses. The results are very good, expense is materially lessened and storage space becomes a minor consideration in mass examinations.

Radiographic images of the chest are usually taken in a summation of all its physical planes, and structures at various depths of the chest are not all seen to the best possible advantage in the film. Various forms of apparatus have been devised to permit better relative definition at predetermined depths in the chest. This is accomplished by having the X-ray tube and the film move in opposite directions to each other at a proper ratio of distances while the chest remains stationary. Structures in all planes, except one, are thereby made to blur and become decidedly less distinct. Structures in the predetermined plane stand out more definitely since there are only blurred shadows of structures in other planes to confuse. Such apparatus has received a variety of names, viz.; tomograph, laminagraph, etc. By their use otherwise undiscoverable cavities are visualized and the questionable presence of cavities determined in the affirmative or negative.

Increasing use of the bronchoscope, an instrument enabling one to look directly into the larynx, trachea or windpipe, and the larger bronchi, has revealed an unsuspected number of tuberculosis ulcers in the trachea and larger bronchi. The presence of tuberculous ulcers in these areas undoubtedly has caused prolonged occurrence of tubercle bacilli in the sputum of some patients when the lung disease apparently was progressing satisfactorily. Such ulcers have been the cause, also, of recurring disseminations or spreads of the disease in the same or opposite lung. With their discovery new methods of local treatment are being tried with varying degrees of success. Some of the ulcers upon subsequent bronchoscopic examinations have been found to be healed. Others apparently were healed at the time of discovery.

Coincident with progress in the discovery and treatment of the disease in the lung, great strides have been made in the detection of the tubercle bacillus, its cause. Methods which heretofore permitted us to say that a patient's lung condition had become arrested since he apparently was not shedding tubercle bacilli, now are known to be faulty. Many patients who have negative sputum by ordinary methods of examination are found to have tubercle bacilli in their sputum when methods of concentration and digestion of the sputum are used. Some who have negative sputum when these latter methods are employed are found to have a positive sputum when the sputum is planted upon culture media suitable to the growth of the tubercle bacillus or when inoculated into guinea pigs. But even when concentration methods and culture fail to reveal tubercle bacilli in the sputum, in a fair number of patients tubercle bacilli may be obtained from the fasting stomach washings. A single specimen of sputum does not seem to be enough. If tubercle bacilli are not found in the total sputum expectorated in one day, they may be found in the total of three days, and if not found then, they may be found in the total specimen of seven days, and so on. In some instances tubercle bacilli apparently are shed from the lung only periodically.

The extraordinary interest in the national campaign against the venereal diseases is increasing and control activities are gaining momentum. For the fiscal year ending June 30, 1939, Congress appropriated to the Public Health Service the sum of $3,000,000 for the fight against these diseases, while a sum exceeding $4,300,000 was made available by state and local governments for the control of syphilis and gonorrhea, to be used to match the Federal funds. For the fiscal year beginning July 1, 1939, the amount authorized by the Venereal Disease Control Act of May 24, 1938, namely, $5,000,000, was appropriated. Available information indicates that the appropriations of state and local health departments for the control of syphilis and gonorrhea will considerably exceed the amount made available to the Public Health Service.

Experience gained during the first year of the Venereal Disease Control Act shows that communities all over the country are being stimulated to meet their part of the responsibility in the campaign against syphilis and gonorrhea. Effective services are being rapidly developed in most areas for the diagnosis and treatment of persons infected with these diseases who are unable to pay private physicians. Some conception of the progress can be had by comparing present services with those available during the year 1936, when the Conference on Venereal Disease Control developed the recommendations for the present campaign.

The blood test for syphilis is one of the most important methods employed in the laboratory diagnosis of the venereal diseases. In the fiscal year 1936 approximately 2,000,000 blood tests for syphilis were performed in the state laboratories throughout the country, as compared with approximately 5,500,000 during the fiscal year 1939.

The development of treatment facilities for the medically indigent is also most encouraging. In 1936, there were only about 1,000 clinics available in the United States for the treatment of patients infected with syphilis and gonorrhea, while in 1939 there were more than 2,200 such clinics. In 1935 approximately 6,500,000 doses of the arsenical drugs used in the treatment of syphilis were sold in this country, while during the calendar year 1938 the number of doses sold increased to approximately 10,500,000.

In recent years great progress has been made in chemotherapy. The new chemical compounds and derivatives of sulfanilamide have been found to be of great value in the treatment and control of gonorrhea. As these drugs occasionally cause untoward reactions, their administration by a competent physician is essential. Enough sulfanilamide was sold in the United States in 1938 to give a week's treatment, consisting of 60 grains per day, to over six million people. It is estimated that not less than 20 to 25 per cent of this amount was used in the treatment of gonorrhea.

Premarital blood tests for syphilis are now required in 19 states, 12 states having enacted such legislation during the year 1938. These laws vary to some extent, and it is possible that a few of them may need amendment. All of them, however, provide for the performance of a serologic blood test for syphilis on both applicants before marriage, this test being part of the physical examination. In most states these laws may be waived under certain conditions when the findings indicate that there is no danger of the transmission of syphilis in marriage, or when it appears that the marriage is in the interests of the public welfare. A law of this kind, if adopted in each of the 48 states, would offer a material contribution to the control of syphilis in marriage.

Another important law added to the statutes of 15 states during 1938 is one requiring that a blood test for syphilis be made on every pregnant woman; 17 states now have such laws. The effectiveness of this legislation is decreased, however, because of the failure of most women to seek prenatal care early in pregnancy; but health departments generally have inaugurated a campaign to teach the women of the country the need for seeking early prenatal care.

The future of the venereal disease control campaign in this country is brighter than ever before. Popular opinion is directing this program in most areas. Public interest is reflected in a statement made in the House of Representatives during the first session of the 76th Congress that 'An expenditure many times over that authorized under existing law could be spent advantageously.' The law authorizes a program with Federal assistance as the basis, but developed slowly and economically with the financial assistance and technical cooperation of state and local governments. See also PUBLIC HEALTH SERVICES.

Recent developments in the study of vitamins have been characterized by rapid elucidation of the chemical properties of several, the discovery of new evidences of human need for certain ones, more satisfactory methods of estimating mild degrees of vitamin deficiencies, a surging interest among physicians in vitamin therapy, commercial exploitation of pure vitamins and concentrates, and a growing interest in the question of food fortification with vitamins and minerals.

At present there are about ten vitamins, or groups of vitamins, of general interest in human nutrition. These are: A, thiamin (B₁), riboflavin, ascorbic acid (C), D, E ( -tocopherol), nicotinic acid, B₆, K and pantothenic acid.

It is indicated that there are at least two substances possessing the biological properties of vitamin A. They are A₁ and A₂. Evidence from molecular distillation indicates that they contain the same number of carbon atoms. Carotene seems to be the precursor of both forms. Some data indicate that A₁ and A₂ do not replace one another with equal readiness in all functions. Deficiency of A may cause a permanent type of blindness associated with constriction of the optic nerve. The dark adaptation or biophotometric method of estimating nutritional status as respects vitamin A appears to be fundamentally sound and practical. By means of this test it has been shown that normal adults on a vitamin A deficient diet develop symptoms of deficiency after 20 to 40 days.

Present interest in thiamin centers on chemical methods of determination, physiological rôle in the body, and therapeutic uses. Recently it has been shown that thiamin functions in the body as a pyrophosphate, called cocarboxylase. The inability of the body to store appreciable amounts of thiamin has been further established. Fat in the diet reduces the requirement for thiamin. In hyperthyroidism the need is increased. Fatty degeneration of the liver has been noted in thiamin-deficient rats and chicks following administration of the vitamin. Apparently the condition is only temporary. It is claimed that excess amounts cause symptoms of manganese deficiency and that feeding extra manganese alleviates the symptoms. Also, it is claimed that large amounts of the nutrient cause sterility in rats. Such reports suggest the need for caution in the use of this potent substance.

Direct proof that riboflavin is needed by humans was afforded by the alleviation with pure riboflavin of characteristic symptoms in humans who had subsisted on a diet known to be deficient in this substance. The first evidences of deficiency are a pallor of the mucosa of the lips and fissures in the angles of the mouth. Deficiency of the factor causes nerve lesions in addition to other effects. Apparently riboflavin deficiency in humans is not uncommon in certain economic levels. It is estimated that the daily requirement of normal adults is about 1 to 2 mg. This amount would be provided by one quart of milk or about two ounces of liver.

One group of investigators has reported interesting studies concerning the origin of ascorbic acid (vitamin C) in animals that do not require a dietary source of the factor. Various terpene-like cyclic ketones were shown to stimulate ascorbic acid synthesis, probably from intermediate metabolites. Beneficial effects have been ascribed to its use in the treatment of lead poisoning. The bodily requirements for it are increased by fever, certain drugs, exercise and elevated environmental temperature.

The number of vitamin D factors remains about ten. Evidence based on the use of radioactive phosphorus suggests that vitamin D action is in bone. Whether it has any specific effect on the intestinal absorption or excretion of calcium and phosphorus is not clear. It has been shown that the vitamin promotes iron utilization. It is reported that growth of children is retarded when they receive amounts of vitamin D as little as four or five times the normal requirement.

Vitamin E ( -tocopherol) has become available in synthetic form. The substance has been shown to have a role in muscle function since experimentally produced muscular dystrophy can be cured with it. The usefulness of vitamin E in human forms of muscular dystrophy has not been clarified.

Rapid progress has been made in the chemistry of vitamin B₆. It was isolated in 1938 and synthesized this year. The formula is 2-methyl-3-hydroxy-4, 5-di(hydroxymethyl)-pyridine. It appears that the factor is metabolically related to the essential fatty acids. It may be very significant that certain common vegetable fats are extremely potent in alleviating the symptoms of B₆ deficiency. Anemia (microcytic hypochromic) has been caused in dogs deprived of B₆. The principal symptom of deficiency in rats is a characteristic dermatitis around the feet and tail. Whether acrodynia occasionally observed in children is related to B₆ deficiency has not been determined.

Vitamin K is attracting much interest at present because it promises to be of use in preventing hemorrhages. A deficiency of the factor is associated with a decrease in prothrombin, a component of the blood clotting mechanism. It may prove useful in preventing the hemorrhagic disease that occurs frequently in newborn infants. An important clue to the structure of K was found when phthiocol, a naphthoquinone occurring in the waxy material of the tubercle bacillus, cured K deficiency. Soon thereafter it was shown that a variety of naphthoquinones are potent. Two naturally occurring antihemorrhagic factors have been isolated, K₁ and K₂. Four different reports of the synthesis of K₁ have been made. It is claimed that a synthetic compound without the phytyl group is more potent than the natural vitamin. Vitamins E and K are closely related chemically.

During the past two years nicotinic acid and certain derivatives have been identified as essential factors in the prevention and cure of pellagra. Substituted pyrazines have been demonstrated to have beneficial effect. This suggests that several compounds having the general properties of nicotinic acid and pyrazine play a physiological role. Rats do not seem to require preformed nicotinic acid. Man, monkeys, pigs and dogs undoubtedly require it, or some related substance. Unthriftiness in pigs on a diet composed largely of corn has been corrected with dramatic effectiveness by the administration of nicotinic acid. It appears that ingested nicotinic acid is utilized for synthesis of the pyridine nucleotides. Liver, lean meat and yeast are rich in nicotinic acid. Milk and wheat germ are good sources.

Pantothenic acid is the name given to an elusive factor found some years ago to be essential in the growth of lower forms of life. Recently it has been identified with the so-called filtrate factor or chick antidermatitis factor. Betaalanine is a constituent of the molecule. Apparently the remaining part of the compound is a hydroxyvaleric acid. A simple bacteriological test for the factor has been devised.

A strange relationship between diet and graying of hair has been indicated. Rats, guinea pigs and puppies have become gray while restricted to certain diets. The graying is cured in a few weeks by injection of so-called filtrate factor. The factor has been found in yeast, rice bran and liver.

Factors W, M, anti-gizzard erosion factor, grass juice factor, and other less well known substances, may prove ultimately to be of much significance, but it suffices only to mention them at present. See also BIOLOGY; BOTANY: Hormones; CHEMISTRY; HORTICULTURE.

The applications of basic information on nutrition have been generally gratifying during the past year. Among dietitians, teachers, public health officials, physicians, and others who influence the public mind, there has been an increasing awareness of the significance of diet in determining the health status of individuals and communities. This is a salutary development, but with the increase in basic knowledge comes added responsibility to protect the public from misuses of the knowledge. It is only through education, both of the public and public agencies, and intelligent legislation, that the public can be protected from uninformed or over-zealous reformers and unscrupulous interests who misrepresent facts and promote half-truths concerning nutrition.

The problem of providing an adequate diet for persons with low incomes has been carefully studied by competent persons in the Federal Government as well as various state and local organizations. Bulletins have been issued by the Federal Government which plan in detail diets to meet the needs of families with subsistence-level income as well as families with better incomes. Certain public and private agencies continue to encourage rural families to consume more of the 'protective' foods such as garden products, milk, eggs and fruit, since they can be produced at little cost for family use where land is available.

Surveys indicate that low-income families tend to spend too much of the food money for meat and out-of-season foods, and too little for milk and vegetables. With the increase in more reliable information on food composition, in terms of dietary essentials, it is becoming possible to make better recommendations concerning the dietetic value of foods.

A promising development in the therapeutic use of proteins has been indicated by reports of the successful parenteral administration of a 'biologically complete' protein hydrolysate. Serum protein regeneration and reduction of edema was readily accomplished in patients who were unable to eat. With the rapid progress in vitamin chemistry it seems probable that the parenteral administration of all nutrients will be possible soon, thus aiding in therapeutics and extending the means of investigating metabolic processes.

That special attention should be given to the diet during pregnancy has been demonstrated anew this year. One investigation showed that pregnant women whose iron intake was kept at a good level had no anemia, but in other women receiving only small amounts of iron there was a considerable incidence of anemia. The majority of instances of anemia during pregnancy appear to be attributable to iron deficiency.

It has been recognized for several years that 'mottled' enamel, a particular type of tooth discoloration, is caused by fluorine ingestion, usually in the drinking water. Recently it has been noted that dental caries (decay) is less prevalent in communities whose water supplies contain considerable amounts of fluorine. Actually it appears that fluorine retards or prevents dental caries. However, fluorine is injurious when the intake exceeds a certain level since it causes 'mottled' or discolored teeth. To control the intake of this element drinking water can be treated with certain chemicals which remove much of the fluorine. Apparently fluorine, as it occurs in drinking water, is more harmful than in certain foods. In the latter it is apparently less available to the body because it is in insoluble compounds.

The health hazard of lead, arsenic and other poisonous substances used in insecticides, continues to receive attention. The degree of toxicity is dependent, in part at least, on the form in which the metals are ingested. For instance, a given amount of lead ingested with apple peel is definitely less injurious than the same amount taken alone.

The effect of various factors on the utilizability of dietary essentials continues to receive attention. Further evidence has been published which shows that oxalates in foods interfere with the utilization of calcium. The hitherto vague relationship between calcium and the utilization of iron has been clarified. Calcium prevents iron from being lost through the formation of iron phosphate.

Extensive studies have been reported on the effect of chronic food restriction on longevity of rats. When they were not allowed to eat all the food they wanted rats lived longer than those allowed to eat ad libitum. But the food-restricted rats experienced a long and enfeebled senescence. The relation of diet to longevity is beginning to attract critical attention. This is an important but difficult field of inquiry.

A natural sequence to the developments in nutrition is the growing interest of the public in concentrated forms of dietary essentials, especially vitamins and minerals. This raises new problems in public health since relatively little is known concerning the tolerance to such concentrated forms of nutrients. Related to this development is the problem of fortifying foods with certain nutrients in order to improve the nutritional qualities of such foods. The desirability of such procedures is still in question since various factors need to be considered.

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