Scurvy Past and Present Part 14

[55] Salant, in experiments on rabbits, found that old or winter carrots did not have the same protective action against tartrates as young carrots, although their diuretic action is the same.

Potato in the amounts usually consumed is a valuable antis...o...b..tic. It is not an exaggeration to state that it is the main antis...o...b..tic bulwark of man. In giving baked potato to children it is commonly advised to use the floury part just beneath the peel; this should be put through a sieve and mixed thoroughly with boiled milk so as to const.i.tute a cream; for younger babies it can be prepared with water to form a diluent similar to the barley water so commonly employed to dilute cow's milk (1 tablespoonful of potato to a pint of milk, cooked for 15 minutes). Little reliance should be placed on beef juice in the usual dosage and none on eggs.

=Cure.=--There is almost nothing in the realm of therapy which is so striking as a s...o...b..tic patient's prompt reaction to antis...o...b..tic treatment. It is all the more marvelous as the cure is effected by means of foodstuffs with which we are accustomed to a.s.sociate no specific virtue. A magic result is seen frequently within 24 or 48 hours. A baby which has had a poor appet.i.te, has been irritable and exquisitely tender, suddenly regains its appet.i.te, is no longer fretful, and can be handled without occasioning crying. Within a week, if the case is mild, all definite symptoms of scurvy may have disappeared, and soon thereafter the infant is thriving and apparently cured. A table is here reproduced (Table 6) from the report of the American Pediatric Society showing the duration of treatment before marked improvement was noticed:

TABLE 6 DURATION OF TREATMENT BEFORE MARKED IMPROVEMENT WAS NOTICED ========================================================== Days Cases Weeks Cases Months Cases ------------------+------------------+------------------ 1 19 1 47 1 6 2 58 2 27 2 4 3 46 3 8 3 4 4 26 4 1 5 19 5 1 6 1 6 1 7 2 8 2 9 1 10 7 12 2 ----------------------------------------------------------

In most instances a gain of weight accompanies improvement. In not a few instances, however, there is a temporary loss or cessation of weight, due in part to an increased excretion of urine. Occasionally there is observed a short exacerbation of the symptoms following the giving of an antis...o...b..tic--a swelling of the thigh or hemorrhage of the gums. A similar phenomenon has been noted in relation to the treatment of polyneuritis in birds and of beriberi in man.

In the cure of scurvy the same dietetic remedies are employed as in its prevention. Orange juice is the sovereign remedy, and should be given in a dosage of about 2 ounces a day.[56] Canned tomato is also most efficacious. If these changes in the dietary are carried out, it is not absolutely necessary to alter the food, although it is advisable to do so. Some writers, for example Neumann and Czerny, treat the disorder by giving milk which has been scalded or brought to the boiling-point.

Others lay particular stress on changing the source of the milk supply, believing that the sameness of the diet leads to the occurrence of scurvy. Such, however, cannot be the case, as otherwise breast-fed babies would be highly subject to this disease. In the report of the American Pediatric Society one case developed on condensed milk and was cured by sterilized milk, and another developed on pasteurized milk and was cured by sterilized milk and broths. These results are explicable; large amounts of milk were given to effect the cure. It may be said in general that in addition to giving fruit or vegetable juices the milk should be either raw or heated to as low a degree as possible (duration of heating as well as height of temperature). Furthermore, the antis...o...b..tic treatment should be continued for a period of months, as the clinical improvement far outstrips the restoration of the bones and other tissues. It seems necessary again to call attention to the fact that too great reliance has been placed on the use of beef juice, which has been shown, both in experiment and in the clinic, to possess comparatively weak antis...o...b..tic properties.

[56] It is difficult to state the exact dosage of orange juice which is necessary. One teaspoonful daily has failed to cure, and rapid cures have been accomplished by giving one tablespoonful. It is well, however, to give a larger amount if it is tolerated.

Orange juice may be given intravenously. This method may be resorted to where the patient is in an advanced stage of the disease or where food cannot be tolerated by mouth; for example, in cases such as that mentioned by Cheadle, where death took place owing to the fact that the antis...o...b..tic could be taken only sparingly, on account of the extreme prostration of the patient. For this purpose the orange juice is obtained in as sterile a manner as possible, boiled for about five minutes and is rendered neutral or slightly alkaline just previous to its injection by the addition of normal sodium hydroxide. Hess and Unger report three cases where this procedure was carried out without the slightest untoward reaction. In one instance, improvement was noted 16 hours after the injection. In view of the novelty of this treatment it may be of interest to cite a case:

A baby 16 months old had hemorrhage of the gums and tenderness of the legs, which were held in the characteristic flexed and everted position. Eliminative treatment was tried without avail; Dover's powder and warmth to promote perspiration; caffeine to promote diuresis; and 2 tablespoonfuls of liquid petrolatum three times a day to increase elimination from the bowels. Intravenous injections of salt solution also proved of no value.

Four intravenous injections of orange juice were given--6 c.c., 12 c.c., 6 c.c., and 35 c.c. As was stated, improvement was noted 16 hours after the first injection. The infant was less irritable, the gums no longer hemorrhagic, and the "capillary resistance test"

(that is to say, the development of petechial spots on the forearm when a tourniquet was applied for 3 minutes to the upper arm) changed from positive to negative.

Harden, Zilva and Still have recommended the use of a concentrated lemon juice for the cure of scurvy, const.i.tuting a form of "intensive"

treatment. In four cases this proved to be of clinical value. Freise has made use of an alcoholic extract of turnips, and Freudenberg of a similar extract of carrots. These preparations did not seem to be markedly potent, and therefore possess no particular therapeutic advantages.

=Non-dietetic Therapy.=--There is little to be done for the patient in addition to the giving of sufficient antis...o...b..tic. No one has reported success with any drug. We have tried the use of atropin, adrenalin, thyroid and parathyroid extracts, cod liver oil, autolyzed yeast, lactose, sodium chloride, calcium chloride, etc., without noting any improvement. Mercurials are stated to be positively harmful, especially when ulcers are present. The patient should be kept in bed, and exertion not allowed on account of the involvement of the heart, which has led to sudden collapse and death. The gums may be treated with nitrate of silver stick or tincture of myrrh. If there is fracture of the long bones with displacement, splints should be applied. Under no circ.u.mstances should hemorrhagic effusions in or about the joints be incised. The patient should be placed in a room which is well aired and lighted, and should be handled and dressed as infrequently as possible, so as to avoid discomfort and pain. It is particularly important that intercurrent infections should be avoided by shielding patients from contact with those who have infectious diseases, especially respiratory infections.

CHAPTER X

METABOLISM

Studies of the chemical exchanges in scurvy have been surprisingly few.

It is a field that should repay investigation, promising to afford a clearer insight into the intermediary metabolism in this disorder. One of the first to touch upon this question was Garrod, who in 1848 reported that there was a diminution of pota.s.sium salts in the urine and in the blood of scurvy patients. In 1877 Ralfe confirmed the pota.s.sium deficiency in the urine, but denied its importance from an etiologic standpoint, as he was unable to benefit scurvy patients by administering pota.s.sium nitrate. He reported an increase of uric acid in the urine, a diminution of the total acidity, and a reduction of the alkaline phosphates. Litten found the a.n.a.lyses of the urine very contradictory in respect to pota.s.sium, but stated that beyond a doubt its uric acid content is increased at the height of the disease, although this diminishes rapidly with convalescence. These few and scattered articles comprise the sum of metabolic studies up to the last decade, and even during the succeeding period they have been very few--so few, indeed, that they furnish insufficient data from which to draw conclusions.

The first careful study of the mineral metabolism in a case of scurvy is that of Baumann and Howard, published in 1912. Its conclusions are not very definite. They may be summed up by their statement that "chlorin and sodium were retained during the fruit-juice period, but excreted in excess of the intake during the preliminary period," and that "more pota.s.sium, calcium and magnesium were retained during the fruit-juice period."

This same year l.u.s.t and Klocman published the first metabolism study of a case of infantile scurvy. The baby was 18 months old and the metabolic changes were investigated during the active, convalescent, and "the healing stage" of the disorder. This study seems to have been carefully carried out. The fact, however, that the infant received 800 c.c. daily of slightly-boiled milk during the active stage, and was improving at this time, may also have had a beneficial effect on the metabolism in respect to scurvy. The results of these writers are surprising--quite different from what they expected or what we should have expected. They write: "The balance of the mineral metabolism, including the total ash, the calcium, phosphorus and chlorin during the florid stage of the disease must be regarded not only as not damaged, compared to that of the healthy child, but indeed as somewhat increased." "All the more striking, on the contrary, are the results found during the stage of convalescence. Here the balances were all markedly negative, and only after a lapse of weeks was the tendency manifested to a return to normal conditions." The authors regard these results as indicating a sort of washing out of "dead material" during convalescence--of material which had gathered during the florid stage of the disease. According to their interpretation the disease is due, not to a primary or secondary salt deficiency, but to a disturbance in salt elimination, and in the first place, of a calcium excretion. This is shown by the fact that even in the "stage of healing," when the total ash and the phosphorus balance once more had become positive, the calcium balance nevertheless remained somewhat negative. The metabolism of infantile scurvy, they believe, far from showing a resemblance to rickets, manifests quite the contrary tendency. The study of this case of infantile scurvy and that of Baumann and Howard of a case of adult scurvy, comprise the total investigation of the metabolism in human scurvy.

In the course of a recent discussion on rickets before the Medical Society of Vienna, Moll states briefly that in a case of infantile scurvy, at the height of the disease, he found a positive calcium balance, which became poor and later negative on giving fruit juice; in other words, a partial confirmation of the work which has just been cited.

In 1913 Bahrdt and Edelstein reported the a.n.a.lyses of the organs of an infant almost nine months old who died of scurvy; an examination of the tissues, especially of the bones, should be most valuable in checking up determinations of the metabolism during life. This investigation runs absolutely contrary to that of l.u.s.t and Klocman. The bones showed a decrease of ash, especially of calcium and of phosphorus, and also a lack of calcium in the muscles, but normal amounts in the liver and in the kidneys. These conditions resemble the deficiency of ash and of lime commonly a.s.sociated with rickets, and it seems quite possible that this infant had rickets as well as scurvy, and that in this way the discrepancy between the two reports is to be explained. The fact that the water content of the bones was two to three times the normal, also lends emphasis to this interpretation. _In any metabolism study of infantile scurvy, great care will have to be exercised that the disorder is not complicated by rickets_, and the issue thereby confused. It will be very difficult to avoid this pitfall, for there is no test by which early rickets can be diagnosed. The danger of this complication may be realized when we bear in mind that the majority of infants have rickets to some degree. An investigation of the chemistry of adult scurvy has an advantage from this point of view.

Chemical examination of the blood has yielded such valuable information regarding metabolic diseases, that it might be expected to shed light on the disturbances of scurvy. The only investigation from this standpoint is that of Hess and Killian, who have reported estimations of the urea, creatinine, sugar, CO_{2} combining power, diastase, cholesterol, chlorine and calcium.[57] The urea content was normal, varying between 12 and 14 mg. per 100 c.c. of blood; this is the average of twenty-one tests on ten cases of infantile scurvy. (In severe cases of beriberi Yano and Nemoti have recently reported that the blood contains an increase of urea, and that its excretion is frequently disturbed.) The creatinine was estimated in two cases and was found to be 2.0 mg. and 1.7 mg. per cent., respectively,--also normal figures. The blood sugar varied from 0.12 to 0.14 per cent. and was examined in almost all the cases in which urea was estimated; these figures are at the upper level of normality (no attention was paid to the interval elapsing between the feeding and the withdrawal of the blood). The diastatic activity was likewise normal. The CO_{2} combining power showed figures under 40 to 45, according to the Van Slyke method, and indicated therefore a mild degree of acidosis. In six cases the chlorides were estimated, the figures being remarkably constant at about 0.42 or 0.43. Cholesterol was a little below normal in the four cases examined. Contradictory results were obtained in regard to calcium. Earlier tests showed a definite deficiency of this salt, but those carried out more recently have generally yielded normal results. Further studies of the blood calcium are highly desirable to ascertain whether it varies in amount in the circulation, and especially in different stages of the disease. This aspect is worthy of particular attention in view of the positive calcium balance noted by l.u.s.t and Klocman during the active stage of scurvy, and the negative balance during the period of convalescence.

[57] Almost all of these cases were receiving liberal daily amounts of cod liver oil, which should exclude the possibility of complicating rickets.

It is evident from the limited data concerning the blood chemistry of scurvy that it is a field which has been inadequately explored and will repay more intensive study. Investigations of this kind have recently been made possible by the introduction of accurate methods requiring only small quant.i.ties of blood.

Studies of the metabolism of animals suffering from scurvy are almost as few as those on man. The work of Morgan and Beger, which is frequently quoted in this connection, is not applicable, as it concerns rabbits, which do not develop scurvy. They found that rabbits fed solely on oats and water suffered in their nutrition (loss of appet.i.te, emaciation, paralysis of hind legs), and could be cured by the addition of sodium bicarbonate to the dietary. In 1916 Lewis and Karr published a paper on the const.i.tuents of the blood and the tissues of guinea-pigs fed on an exclusive oat diet. They found the urea content several times greater than normal, but that it fell to normal once more if cabbage or orange juice was given. From the standpoint of scurvy, this investigation is open to the criticism that the diet was too incomplete, and also, as the authors suggest, that the animals suffered from partial starvation and a lack of water.

In the following year Karr and Lewis published a paper on a different phase of this subject, and came to the following conclusions: "No changes in urinary elimination of phenols, nor in the degree of conjugation of the phenols, were observed, provided the factor of partial starvation was ruled out. This is believed to indicate that no increased bacterial action occurs in the intestine of s...o...b..tic guinea-pigs despite the difficulty of evacuation of the faeces." These results are in harmony with the bacteriological study of Torrey and Hess, who found that there was no increase in the proteolytic flora of the intestine in infants or in guinea-pigs suffering from scurvy.

In 1917 Baumann and Howard published the only metabolism study which has been carried out on guinea-pigs suffering from scurvy, and they are of the opinion that this disorder has a profound effect on the mineral metabolism of this animal. The calcium was excreted in notably large amount; pota.s.sium was also lost, and to a greater extent than sodium; the only element which was consistently retained during the active stage as well as during the period of recovery, was magnesium. This study was followed shortly by one from the same laboratory, by Howard and Ingvaldsen, carried out on a monkey suffering from scurvy. It was inconclusive, not conforming to the experiments on the guinea-pigs; the authors state that the "changes in the mineral excretion of the monkey during the s...o...b..tic period were not sufficiently significant to admit of easy interpretation." "The marked loss of the various mineral substances encountered in experiments with man and guinea-pig was not observed in the present series." It should be remembered, however, that the diets of the guinea-pigs and the monkeys were quite different, the former consisting mainly of oats, and the latter of condensed milk. It is quite possible that the basic diet may play a role in the metabolism of this disease, although, as stated elsewhere, its effect cannot be noted clinically. Special attention should be paid to this factor in metabolic studies, in view of the widely-held opinion that the carbohydrates exert a potent influence in the development of beriberi.

The investigations of the nitrogen metabolism in man and in animals have been most unsatisfactory. The two on human beings--an infant and an adult--were negative; that on guinea-pig scurvy cannot be utilized on account of the restricted diet of oats, which contained insufficient nitrogen, whereas the one on the monkey showed some loss of nitrogen, which led the authors to suggest an increased nitrogenous catabolism in scurvy. This comprises the total data on this subject.

Summarizing the results of these few metabolic studies, it may be stated that they harmonize on one point only--the positive balance of calcium during the active stage of the disease. The investigation of Baumann and Howard on adult scurvy, of l.u.s.t and Klocman and of Moll on infantile scurvy, and of Howard and Ingvaldsen on the monkey, are all in agreement in this important conclusion.

CHAPTER XI

RELATION OF SCURVY TO OTHER DISEASES

In the foregoing there has been frequent reference to the close relationship between scurvy and the incidence of the infectious diseases--to the fact that a s...o...b..tic condition increases the susceptibility to infection. This is indeed one of the most characteristic, as well as one of the most important phenomena a.s.sociated with scurvy and other disorders resulting from vitamine deficiency. Mention has been made of the special susceptibility to the diphtheria bacillus, and to the organisms leading to coryza and the respiratory diseases, but no doubt this applies also to invasion by other bacteria. We wish, however, to confine ourselves to the nutritional disorders, first in their relationship one to the other, and second, as a group of deficiency diseases, due to a lack of vitamines of various kinds. As is well known, in addition to scurvy, this group generally includes beriberi, a disease attributed to a lack of the water-soluble vitamine, and xerophthalmia, an eye condition which recently has been brought about in rats by placing them on a diet free from fat-soluble vitamine. These, however, form only the nucleus of the disorders which commonly are included in this category. Schaumann, the first to formulate this cla.s.sification, ill.u.s.trated his conception of the interrelationship by depicting the various members as spokes of a wheel surrounding a central hub. He included scurvy, rickets, osteomalacia, typical beriberi, ship-beriberi, pellagra and mehlnaerschaden. Funk made a similar cla.s.sification of disorders which he termed the "avitaminosen." There is a tendency to enlarge rather than to decrease the membership of this cla.s.s, and recently war or hunger edema, infantile atrophy and diarrhoea, sprue, coeliac disease, leprosy and others have been proposed as suitable candidates. At the present time it is impossible to determine which and how many of this motley company should be a.s.sociated with scurvy. Some, possibly, are the result of a lack of vitamine, but for the present it will be well to bear in mind that three vitamines only have stood the test of experiment, and only these three therefore can be definitely connected in a causal relationship with pathologic conditions. In addition to this consideration of the interrelationship of the "deficiency diseases," the kinship of allied disorders--more particularly of rickets--must be discussed.

Although at first thought _beriberi_ and scurvy would seem far apart from a clinical point of view, they have some important features in common. In both there is a tendency to a rapidity of the heart's action and a marked lability of the pulse, to an enlargement of the cardiac ventricles, to an involvement of the vagus, and to an exaggeration of the deep reflexes. It is unnecessary to describe these signs and symptoms in detail, as they have been fully considered under symptomatology. It has been recorded from time to time that under certain circ.u.mstances scurvy has developed in man where one should have expected beriberi, and _vice versa_. Darling, who has had a large experience in this field, writes: "A deficient dietary in a tropical African negro mine laborer causes severe scurvy, in a Cape Colony African mine laborer, mild scurvy, and in some African negroes a diet that causes scurvy in one set of men causes neuritis in others."

Possibly some minor differences in the dietary can explain this difference in reaction--for we do not know all the sources of the water-soluble vitamine, but such an experience deserves to be cited as it is not an isolated instance. It is all the more worthy of attention because it harmonizes to a certain extent with the everyday experience of animal investigation. As has been stated elsewhere, a diet of decorticated grain will lead to scurvy in the guinea-pig, to polyneuritis in the pigeon, and to a combination of these diseases in the hog! Results of this kind show that there must be a relationship between the etiologic factors of scurvy and of beriberi. It is unwise at present to attempt to define the relationship more precisely. The remarkable observation, first made by Fuerst, and since confirmed by numerous investigators, that seeds and legumes are devoid of antis...o...b..tic potency but acquire this power on sprouting, const.i.tutes another link in the evidence of their kinship. Funk has suggested that the antis...o...b..tic vitamine can be formed from the "antineuritic"

vitamine, a theory which is very attractive but needs confirmation and experimental proof. It is quite evident that this change does not usually occur in animals, in view of the specificity of the vitamines for their respective diseases--of the antis...o...b..tic for scurvy and the water-soluble for beriberi.

It will be noted that "_ship-beriberi_" is included in this group of diseases. Very little is known about this condition, except what is contained in the investigation of Nocht (1903) and that of Holst and Froelich. It is a very rare condition but of interest because it is characterized by spongy, hemorrhagic gums and other signs encountered in scurvy. The feature which differentiates it sharply from scurvy, however, is an anaesthesia of the extremities. Ship-beriberi is generally regarded as a combination of beriberi and scurvy. Where these two disorders occur concomitantly, the beriberi manifests itself some months before the scurvy, as the latter takes much longer to develop.

In considering the vitamines in connection with diseases of the nervous system, mention may be made of "central neuritis" and the "peripheral neuritis" which has been reported from the West Indies. This bears only a partial resemblance to beriberi, as there is no edema, nor dyspnoea, and its course is more chronic. Judging from the report of Edwards from Jamaica, the cases more closely resemble pellagra, terminating after many years. A degeneration of the cells of the spinal cord was found and "in some isolated patches of the cerebellum and in the roots of the optic and auditory nerves." The disease occurs among the poor cla.s.ses whose diet is inadequate chiefly in nitrogen.

Eijkman was the first to draw an a.n.a.logy between beriberi and _pellagra_, and thus to suggest that the latter might be a disease due to an unidentified factor; he compared the pernicious effect of a diet of polished rice with that of decorticated corn. Of recent years, largely as the result of the investigations of Goldberger and his co-workers, pellagra has come to be regarded as a dietetic disorder primarily due to a lack of adequate protein, rather than to a lack of a specific vitamine. Its relationship to scurvy cannot, therefore, at the present time, be discussed from an etiologic viewpoint. Apart, however, from the question of etiology, the two diseases have certain clinical symptoms in common. Weston states that "distinguished physicians, who were really astute observers, have mistaken pellagra for scurvy, eczema, various kinds of intestinal troubles, syphilis, and many other diseases." In the chapter on symptomatology, attention has been directed to the fact that an eczema which yields to antis...o...b..tic treatment may occur in scurvy; at times it presents the symmetrical arrangement so typical of pellagra. In other cases a fleeting erythema may be observed, another sign noted frequently in pellagrins. In some instances congestion of the gums has been recorded. In describing a little girl of three who had pellagra, Weston writes: "The gums are also red and swollen, suggesting scurvy." This child had eaten large amounts of turnips, so that there could have been no question of complicating scurvy. Lombroso and some of the earlier authors drew attention to the fact that fragility of the bones, of the ribs and of the long bones, was often a.s.sociated with pellagra. These various clinical similarities should not be construed as evidence in favor of the "avitamine" nature of pellagra. They indicate, rather, that in nutritional disorders, whatever may be their underlying cause, the vessels, the bones, and other tissues may suffer and lead to similar--but not identical--clinical pictures.[58]

[58] There is no adequate reason for placing in this group "coeliac disease," a nutritional disorder of children recently described by Still, and suggested by McCarrison as belonging to the category of the vitamine deficiency diseases. A case of this kind has come to our attention which resembled pellagra in many respects. It showed the bright red, denuded tongue, the intestinal symptoms, the occasional edema, marked loss in weight, and evanescent erythema--all symptoms of markedly disturbed nutrition but not distinctive of a lack of vitamines.

The relation between scurvy and rickets is a subject which was discussed by Glisson. With the renewed interest in infantile scurvy which followed Barlow's work toward the end of the last century, children's specialists ranged themselves into opposing camps on the question of the interrelationship and interdependency of these two diseases. Some accepted Barlow's dictum that infantile scurvy is an absolutely distinct and separate ent.i.ty; others, for example, Hirschsprung, declared that the so-called scurvy was merely a form of rickets; whereas a third group considered it a combination of rickets and scurvy. This last viewpoint was actively maintained by Cheadle on the clinical side, and later by Schoedel and Nauwerk on the pathologic side--the latter declaring that rickets is "an inseparable component of infantile scurvy," and that the entire disease should be regarded merely as "an episode in the course of rickets." Even Barlow, in a paper published in 1894, wrote: "Rhachitic changes already present may act as a physiological determinant of the sites in which scurvy becomes manifest" and "rickets as a basis plus inadequate food gives the simplest explanation of the typical case" (of scurvy).

We had an exceptional opportunity to test this thesis in 1914, in an inst.i.tution where scurvy broke out among infants who were on a diet of pasteurized milk. All these infants were receiving cod liver oil daily, as prophylactic treatment against rickets. Many infants have been seen since that time, who in spite of receiving cod liver oil developed scurvy, and others in whom large doses of this oil failed to mitigate the scurvy, although it prevented rickets. The same failure has been encountered in the treatment of scurvy in guinea-pigs. This experience has been without exception, both from a prophylactic and a curative standpoint.

Confusion between the two diseases has resulted from the fact that the majority of infants in the Temperate Zone have some degree of rickets.

Thus the two diseases have been found very frequently a.s.sociated in pathologic examination of the bones, leading some to infer that they are in some way interdependent. They have been also confused clinically, as mentioned in another connection, owing to the fact that beading of the ribs--the rhachitic rosary--has been mistakenly regarded as a pathognomonic sign of rickets, whereas it is also a sign common to scurvy. It is important to bear in mind that from the pathologic viewpoint scurvy and rickets present strikingly dissimilar pictures--the former is characterized by an almost complete cessation of activity of bone-forming elements, whereas the latter is distinguished by a hyperplastic condition leading to a marked overgrowth of cartilage and of abnormal bone. Viewed from the pathologic, etiologic and clinical standpoint, we believe that there is no basis for a.s.suming an interrelationship between the two disorders, and that scurvy will develop as readily and as rapidly where rickets is absent as where it is present.[59]

[59] The only evidence in favor of a true interrelationship is furnished by a necropsy report of Hart and Lessing on one of five monkeys fed on a s...o...b..tic diet. This animal died of disseminated tuberculosis, and the bones showed "the cla.s.sic picture of severe rickets." This occurrence cannot be explained, although illness and lack of exercise no doubt played a role. Until similar cases are reported, the incident must be regarded merely as interesting and suggestive.

It is premature to discuss the relationship of these two disorders from the vitamine standpoint. In 1910 Schaumann suggested that rickets was due to a lack of a specific food factor, and somewhat later Funk included it among the "avitaminosen." Recently Mellanby, as the result of experiments on dogs, has affirmed that the fault lies in a lack of the fat-soluble or a closely-related vitamine. Investigations of the near future will probably decide the merits of this contention; our experience is that rickets develops in infants even where the diet contains adequate fat-soluble vitamine. If rickets is proved to be a disorder depending on a vitamine, it belongs, naturally, in the same group as scurvy. This would indicate relationship, but not interrelationship. Just as the mere fact that a lack of vitamines leads to scurvy and to beriberi does not signify, in theory or in practice, the existence of pathogenetic interrelationship. However, as stated, this is a subject which does not as yet rest on a secure foundation.

_Osteogenesis imperfecta and osteomalacia_ are disorders of dietetic or metabolic origin characterized by fragility of the bones. The latter has developed new significance and importance due to its increased occurrence in almost epidemic form in the Central Empires at the close of the World War. The etiology of both disorders is most obscure. In the future in considering their pathogenesis it will be well to draw a sharp distinction between them. Osteogenesis imperfecta is a disease in which an injury occurs to the foetus without any manifest illness in the mother, which seems to indicate a primary lesion of the foetus (perhaps metabolic); osteomalacia, on the other hand, attacks the mother who gives birth to an apparently healthy foetus. The latter gains added interest because it is a disease of the bones which is attributed to dysfunction of the endocrine glands, to a disturbance especially of the parathyroid. If this observation is confirmed, it furnishes another anatomical basis for a.s.sociating the glands of internal secretion with pathologic conditions of the bones.

One cannot survey the various diseases of the bones--scurvy, rickets, osteoporosis, osteogenesis imperfecta, osteomalacia, etc.,--without realizing that this group is at present in a state of great confusion and will have to be rearranged and winnowed. The differentiation between some of these diseases is not in every instance clear morphologically--for instance, early cases of scurvy and osteoporosis--so that it is difficult to consider them satisfactorily from the standpoint of pathogenesis. Clinical differentiation is still more difficult and uncertain. It seems probable that new ent.i.ties will be established, as has happened in the past. It is not so long since rickets included almost all the bone diseases of infants. Gradually congenital syphilis, scurvy, and achondroplasia were segregated as distinct diseases. Probably a similar separation of other pathologic conditions, now so entangled as to be indistinguishable, will be evolved.

Among the diseases which have been attributed to a vitamine deficiency are "war or hunger edema," sprue, the "mehlnaerschaden" of infants, and the "exudative diathesis" described by Czerny and Keller. Future investigation will disclose whether any of these disorders belong in the group with scurvy. The _hunger edema_, noted in the late war and in previous wars, seems to be a complex condition, quite dissociated from scurvy, as many of the sufferers consumed comparatively large quant.i.ties of potatoes or other vegetables. The "_mehlnaerschaden_" resembles scurvy and the other vitamine disorders in its tendency to produce hydremia and susceptibility to infection. It also develops in spite of a liberal supply of antis...o...b..tic foodstuff in the dietary. As its name implies, it comes about on a diet containing large quant.i.ties of carbohydrate, of the cereal paps so commonly fed to infants. It is conceivable that an unbalanced diet of this kind may not provide a sufficiency of all the vitamines.