antibiotics and iatrogenic disease · antibiotics and iatrogenic disease by t. e. roy, m.d....

ANTIBIOTICS AND IATROGENIC DISEASE

By T. E. Roy, M.D.Department of Bacteriok’gy, the Hospital for Sick Children, and the Department of Bacteriology, the

University of Toronto

164 IATROGENIC DISEASE

ADDRESS: 555 University Avenue, Toronto, Ontario, Canada.

That the early feeding of egg white favors

the development of sensitization is widely

accepted. Some pediatricians-myself in-

cluded-feel that the too early introduction

of other solid foods also favors the develop-

ment of allergy.

The matter of adenoid-tonsillectomy in

the allergic child is one of frequent con-

cern. Some physicians feel that this opera-

tion should not be done in allergic children,

or in children of allergic parents, during

the height of the pollen season, as pollen

sensitization is then more likely to occur.

This may be a valid precaution, especially

in areas where the pollen count rises to

great heights. Not valid, in my opinion, is

the avoidance of needed adenoid-tonsillec-

tomy simply because the child is allergic-

on the theory the allergy may be flared up-

or the performance of the operation rou-

timely in allergic children. I believe the in-

dications for operation are the same in al-

lergic and non-allergic children; the reten-

lion of obstructing adenoid tissue is no more

logical in an allergic child than in one who

is nonallergic.

Finally, I would like to venture the view

that just as the retention of obstructive ade-

noid tissue is not logical, retention of a

pet to which a patient is sensitive is equally

illogical. There is no question, in my mind,

that by condoning such an arrangement we

physicians have permitted a great deal of

T HE A5SOCIATION of the term “iatrogenic

disease” with the clinical use of anti-

biotics poses many problems.

Physicians generally are familiar with

most of the untoward reactions that may

follow the use of antibiotics, and many ex-

asthma to persist in our patients. I have

seen much more harm done in this way

than is done psychologically by the removal

of the dog or cat from the homes of asth-

matic children. Our patients and their par-

ents are like ourselves in wanting to have

their cake and eat it, too. They would like

to get rid of asthma, while keeping the

cause of it. The attempt to do so is no more

successful in this situation than it is in oth-

ers like it. As physicians, it behooves us

not to become party to this type of self-

deception.

A discussion of this type would not be

complete without mentioning the potential

danger of giving horse serum or other serum

to sensitized patients. Such sensitization

may have been induced by previous ad-

ministration of serum or may have occurred

naturally, as in the case of a horse-sensitive

asthmatic. It is, therefore, necessary to ques-

tion the recipient about known sensitivity to

horses, as well as previous administration

of serum. Intradermal testing of such pa-

tients will reveal those in whom serum ad-

ministration may be dangerous. Foremost

among these is the horse-sensitive asthmatic

whose skin test is markedly positive. Ordi-

nary delayed serum sickness in a previously

untreated patient following therapeutic

doses of diphtheria or tetanus antitoxin is

an example of justifiably induced iatrogenic

disease.

cellent reviews of the subject are to be

found in the literature.14

One cannot divorce the undesirable ef-

fects of antibiotics from the beneficial ones

and, in this light, therapy becomes a calcu-

lated risk. If the probable discomforts or

by guest on June 25, 2020www.aappublications.org/newsDownloaded from

AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 165

dangers outweigh the probable advantages,

the cure may be worse than the disease, and

one is then dealing with true iatrogenic dis-

ease.

Probabilities of this kind cannot be as-

sessed easily with antibiotics because reac-

tions vary so much with type of drug, dose,

course, method of giving and in different

patients. Certain reports may be biased one

way or the other because of personal preju-

dices or unusual series. Some ill effects are

undoubtedly related to unwise, improper

or careless use of the drug; others are not.

So true incidences are not accurately

known. Reactions where antibiotics are be-

ing used needlessly for trivial infections or

for unnecessary prophybaxis are particularly

deplorable while risks are justified when

dealing with severe infections known to re-

spond. Evaluation is difficult with infections

of borderline severity and those prone to

exceptionally severe secondary bacterial

complications.

Reactions may be mild or severe; none is

negligible. Oxytetracycline, for example, is

considered to be relatively harmless. Still,

Jackson and his colleagues5 reported that

58% of patients with pneumonia showed un-

toward effects attributable to this antibiotic.

Most reactions were mild, but the antibiotic

was believed to have contributed in large

measure to the fatal outcome in five of the

seven patients who died in the 91 cases.

Tissue irritation and pain from injected

drug is often regarded as warranted tempo-

rary inconvenience to the patient. The in-

tensity of these reactions is usually less with

the soluble preparations such as potassium

pencillin and streptomycin than with re-

pository forms such as procaine penicillin,

benzathine penicillin C and suspension of

chboramphenicol. The pain from some, nota-

bly bacitracin and polymyxin B, is disguised

by mixing with procaine. There is often

neglect of the deleterious mental and physi-

cal effects that pain might have on sick in-

dividuals particularly if bong courses of

therapy are given.

Not all local irritant reactions are so

easily disregarded. Residual areas of degen-

eration and fibrosis in muscles have been

seen, but are seldom booked for. Sterile

abscesses have followed the injection of

preparations in oil. One report suggests,

maybe wrongly, that metastasizing fibro-

sarcomas arose in two patients at the sites

of intramuscular injections of penicillin in

sesame oil because of a carcinogenic effect

from the oil.6 Four papers71#{176} describe se-

vere neuritis in 15 infants and adults where

sensory losses and/or disabling motor pa-

ralyses followed intramuscular injections of

penicillin, streptomycin or tetracycline. The

disabilities persisted for months in some

cases and in a few seemed permanent. The

sciatic nerve was involved most frequently,

following intragluteal injections, but the

deltoid region was affected in five cases. In

some patients the immediate onset of symp-

toms suggested a more or less mechanical

type of injury; in others, notably after in-

jection of penicillin, the symptoms appeared

only after several days, leading to a belief

that the effect was rebated to the known

toxicity of penicillin for nerve tissue.’1 We

are aware of several unreported cases. This

complication is admittedly of infrequent

occurrence, but the consequences are dis-

astrous.

Toxicity to the central nervous system

evidenced by spasms, convulsions and coma

and by persisting paralyses in survivors, has

followed intrathecal injections of penicil-

un where the dose greatly exceeded 5,000

to 10,000 units.12 Somewhat similar reac-

tions have resulted from excessive intrathe-

cal doses of streptomycin.13 Febrile reac-

tions with pleocytosis in the spinal fluid

are often seen with usual intrathecal doses.

Most antibiotics can be given orally, thus

avoiding painful and other tissue reactions,

but with certain drugs this unfortunately

results in a higher incidence of various

gastrointestinal complications that are more

troublesome and significant than those after

parenteral use. The so-called “broad spec-

trum” drugs are the chief offenders, though

others may be involved, and these side ef-

fects are not always controllable by adjust-

ments of dosage. The mechanisms underly-



ing these complications are poorly under-

stood. Some of the effects are rebated to a

change in the normal bacterial flora of the

tract;14 others are not. Some may be due to

a direct irritation of the gut or to an upset

in the absorption or utilization of certain of

the vitamin B components.

Nausea or nausea and vomiting may be

very upsetting, occurring in 15% of Jackson’s

series5 with oxytetracycine. Various forms

of gbossitis and stomatitis are seen; these

occurred in 2% in Jackson’s series.

But far more troublesome, persistent and

sometimes serious are the disturbances of

the lower intestinal tract. The incidence of

anorectal-colonic side effects has been esti-

mated as about 20% in those taking broad

spectrum antibiotics, though much less with

other drugs. In Turell’s experience,15 about

57% of those showing upsets of the lower

gastrointestinal tract have perianal pruritis

alone, about 27% have diarrhea and 16%

have both pruritis and diarrhea.

Perianal pruritis is common, even early in

ambulatory patients, and though not fatal

some sufferers almost wish it were. It usu-

ally disappears within 1 or 2 weeks after

discontinuing the drug, but recovery may

be slow in as many as 30%. A few may re-

main problems for several months despite

active treatment with topical cortisone or

other therapies.16

Diarrheal upsets vary from bothersome,

loose, frequent stools to severe, toxic, dys-

enteric-like diseases. The mild upsets, seen

often with trivial treatment for trivial in-

fections, may appear early and persist for

weeks after discontinuing the drug; the Se-

vere types may be rapidly fatal. Dearing

and Heilman17 recorded 7 deaths in 29 such

severely affected patients; 4 in the 12 re-

ceiving antibiotics for preoperative prepa-

ration of the intestine and 3 in the 17 being

treated for various diseases. The fulminat-

ing, disastrous reactions are usually accom-

panied by partial or complete replacement

of the intestinal flora by staphybococci.18

Most such cases of entercolitis will respond

promptly if a suitable antibiotic capable of

suppressing the staphylococcus is given

early, but minor disability may persist for

a long time. Quick tentative confirmation of

the diagnosis of staphybococcal enterocolitis

is best made by a direct microscopic exami-

nation of a stained film of the feces. Re-

placement of the intestinal flora by staphy-

lococci can occur without giving rise to the

disease.

Toxicities directed systematically at spe-

cific organs are seen. Infrequently occur-

ring, miscellaneous, sometimes fatal reac-

tions have been reported for most antibi-

otics, such as damage to the liver by exces-

sive administration of chbortetracycline in-

tr2O or by novobiocin.21 These

are often difficult to assess because factors

related to dose or to the abnormal physio-

logic state of the patient may contribute

greatly to the effects in each individual.

Maybe the action of chboramphenicol on

the hematopoetic system should be men-

tioned here even though further experience

suggests that the dangers from this drug are

not as great as was once thought.2225

Some toxic manifestations, however, al-

most constantly accompany the parenterab

use of certain antibiotics. Included here are

the nephrotoxicity of 2627 the

transient nephrotoxicity from bacitracin,28

and the less marked renal effects from poly-

myxin B.29 These drugs should not be used

or cautiously used in patients with impaired

renal function. The ill-defined paresthesias,

vasomotor and psychic upsets accompany-

ing systemic administration of polymyxin

B29 are examples of neurotoxicities, but the

best known of the neurotoxic effects are the

vestibular and auditory disturbances after

administration of streptomycin and dihydro-

streptomycin.3#{176}33

The ill effects of the streptomycins vary

with the dose, the duration of therapy and

the ability of the kidney to excrete the

drug. From 44 to 96% of patients receiving

a 4-week course of streptomycin may

show vestibular disturbances depending on

whether 1 gm or 2 gm are given daily. This

is largely reversible, but residual defects

may remain in 50% of affected subjects.’�

With dihydrostreptomycin, auditory dis-



turbances become more prominent than

vestibular ones, and while these are slower

to appear they tend to be more irreversi-

ble. The drug, neomycin, is particularly

prone to give irreversible nerve deafness if

given parenterally,26 and many patients may

remain “stone” deaf. These dangers from

streptomycin are disturbing when one con-

siders how frequently fixed combinations of

streptomycin and penicillin are given to in-

fants and how hard it is to recognize early

impairment of the eighth nerve in the very

young.

Drug fever due to antibiotics is proba-

bby common, although seldom recognized

as such. Its significance may be that it is

often responsible for undue prolongation of

a course of therapy.

Reactions to antibiotics attributable to al-

lergic or hypersensitivity mechanisms are

distinct 2, 35 They are, perhaps, re-

bated more closely to iatrogenic disease

than most toxic manifestations of antibiotics

because they may follow the first dose of

the drug, even in individuals who are re-

ceiving such therapy for trivial reasons.

These reactions may take many forms : van-

ous rapid or delayed skin manifestations

running the gamut from simple erythemas

through eczematoid and urticarial eruptions

to exfoliative dermatitis; miscellaneous re-

actions; and anaphylactoid shock that is

often fatal. The risks involved are estimated

variously by different reporters, but the in-

cidences are highest with penicillin, much

lower with streptomycin and very bow with

the others. Novobiocin has produced a high

incidence of skin rashes, possibly allergic

in 637

After an injection of penicillin, it has been

said38 that some reaction may be expected

in 2.5% of children, in 5% of non-allergic

adults and in 15% of individuals with an al-

lergic diathesis. The risk from oral adminis-

tration is less, estimated at about 0.2%. Re-

action rates are said to be increasing by 1%

each year, possibly because of prior sensi-

tizing doses of penicillin. Reactions occur,

however, in individuals not known to have

received penicillin previously.

Anaphylactoid shock has been reported

most frequently after the use of penicillin;

all types of preparations have been involved

including the crystalline potassium salt. Von

Oettingen,1 from the literature published

prior to 1953, lists 127 such penicillin reac-

tions; 46 were fatal. Seventy-two of these

reactions with 24 fatalities were related to

procaine penicillin. There was little to im-

plicate the procaine part of the molecule,

but one might ask how often this relatively

insoluble salt might have been injected in-

advertently into a vein, a danger that has

been shown by Kagan to exist experi-

mentally.39 Almost all anaphybactoid reac-

tions occur after injection of penicillin, but

death has followed oral administration,40

and severe reactions have resulted from skin

contact.41

Estimates of the incidence of hypersensi-

tivity reactions to streptomycin have varied

from 0.4 to 5%. The commonest type is that

reported by the British Ministry of Health42

where skin reactions occurred in 3.5% of

nurses who were handling streptomycin.

Von Oettingen lists seven anaphybactoid

reactions to injected streptomycin with two

fatalities. There was one nonfatal reaction

to chbortetracycline.

There are many other untoward effects

of antibiotics that come about somewhat in-

directly but which may nevertheless be

classified properly as iatrogenic disease.

These are the so-called replacement infec-

tions or supeninfections. Most are related to

disturbances in the normal flora of the body

that follow antibiotic therapy.” On occa-

sions these added infections are of endoge-

nous source, but more frequently their

source is exogenous, and here another fac-

ton enters the picture of iatrogenic disease.

This factor is our inability to protect hos-

pitalized patients from the bacterial en-

vironment of the hospital, an environment

which, because of the very nature of hospi-

tabs, abounds in microorganisms of selected

virulence and of selected patterns of resist-

ance to antibiotics. Cross infection, the

widespread, often indiscriminate use of an-

tibiotics, the emergence of antibiotic-resist-



ant bacteria are all interrelated phenomena

that lead to the greater prevalence of super-

infections in hospitalized patients than in

those outside hospitals. The chief offenders

in these infections are staphylococci,�3 but

many other microorganisms including Can-

dida albicans may be involved.”

The true incidence of new infections

developing during antibiotic therapy and

as a more or less direct result of that

therapy is not lcnown. Weinstein and col-

leagues,�� in a careful study of 3,095 pa-

tients, estimated the frequency as 2.19%.

These occurred most commonly in children

and usually after giving broad spectrum

antibiotics. They often arose withn a few

days of starting therapy.

Antibiotics are often given for prophy-

laxis, the view being taken that this could

benefit the patient without having harmful

effects. This prophylaxis may be justified

where one is dealing with specific infections

such as those caused by hemolytic strepto-

cocci, or those due to meningococci, gono-

cocci and a few others. There is little justi-

fication for antibiotic prophylaxis against

the bacterial world at large. There is almost

no evidence to support antibiotic prophy-

baxis during most of the common viral in-

fections, including the common cold, atypi-

cal pneumonia, measles or poliomyelitis, nor

during bacterial infections such as pertussis,

or in clean elective surgery or where in-

dwelling catheters or drainage tubes are

used. Weinstein’s studies45 indicate that

such prophylaxis may in fact be harmful.

Of 130 patients with measles receiving anti-

biotics prophylactically, 30.4% developed

superimposed bacterial infections whereas

this occurred in only 14.9% of 298 cases not

receiving antibiotic. Complicating infections

developed in only 16% of 165 cases of bulbar

poliomyelitis not receiving drug, but in 53%

of 63 similar cases who were given antibi-

otics. This unwise prophylaxis does little

more than insure that the superimposed in-

fections will be resistant to the antibiotics

used.

The needless prescribing of antibiotics is

wasteful; it is dangerous because reactions

may occur or the patient may become spe-

cifically sensitized. At the army post in the

village of Igloo, South Dakota,�6 two enter-

prising doctors, Nolen and Dille, tried to

determine if an abuse had been made of

antibiotics among the residents of the vil-

lage. There were 763 civilians who had

lived in Igloo for a full 5 years, who had

been employed at the army post. Of these,

only 7.9% had never received antibiotics

during the 5-year period. Among those who

had taken antibiotics, the average number

of occasions each individual had been so

treated was 3.9 times. Fortunately the medi-

cal records of this group were available to

decide if antibiotic use had been warranted.

The two doctors were most gentlemanly,

even allowing a 1#{176}rise above normal in

temperature to be a valid reason for treat-

ment. Despite their generosity, they con-

cluded that antibiotic therapy had not been

indicated on 52.5% of occasions.

We don’t know how much good or how

much harm was done in Igloo, South Da-

kota, but we suspect that there was dis-

honest thinking, albeit not conscious dis-

honesty. There may be a moral to be drawn

from Igloo, but there is no need to spell it

out here.

These then are some of the highlights of

the topic, “Antibiotics and Iatrogenic Dis-

ease.” The dangers and discomforts attend-

ing antibiotic use are many and varied-

sensitization and hypersensitivity reactions,

pain and other local effects, systemic toxic

effects, the hazards of supeninfections and

replacement infections, and others. These

are real hazards that should be stressed as

well as the benefits. Because they are real,

the giving of antibiotics is always a calcu-

lated risk and they should be used only

when there are definite and valid indica-

tions.

REFERENCES

1. von Oettingen, W. F. : Symposium onnewer aspects of antibiotics : Complica-

lions of antibiotic therapy. Am. J. Med.,18:792, 1955.

2. Kagan, B. M., and Faller, L. : Symposium

on clinical advances in medicine; unto-



ward reactions to antibiotics. M. Clin.North America, 39:111, 1955.

3. Kagan, B. M., et al. : Symposium on anti-

microbial therapy. Pediat. Clin. NorthAmerica, May, 1956, p. 221.

4. Finland, M., et al. : True significance and

real incidence of reactions followingclinical use of antibiotics: Panel discus-

sion. Antibiotics Annual 1955-1956, p.

967.5. Jackson, G. G., et al. : Terramycin therapy

of pneumonia: Clinical and bacteriologicstudies in 91 cases. Ann. mt. Med., 35:1175, 1951.

6. Goldenberg, I. S. : Penicillin in sesame oiland fibrosarcoma: A report of two cases.

Cancer, 7:905, 1954.7. Kolb, L. C., and Gray, S. J. : Peripheral

neuritis as a complication of penicillin

therapy. J.A.M.A., 132:323, 1946.

8. Broadbent, T. R., Odom, G. L., and Wood-hall, B. : Peripheral nerve injuries fromadministration of penicillin; report offour clinical cases. J.A.M.A., 140:1008,1949.

9. Matson, D. D. : Early neurolysis in thetreatment of injury of the peripheralnerves due to faulty injection of anti-biotics. New England J. Med., 242:973,1950.

10. Scheinberg, L., and Allensworth, M. : Sci-

atic neuropathy in infants related to

antibiotic injections. PEDIAmIc5, 19:261,1957.

11. Pilcher, C., Meacham, W. F., and Smith,

E. R. : Epileptogenic effects of penicillin;an experimental study. Arch. mt. Med.,79:465, 1947.

12. Walker, A. E. : Toxic effects of intrathe-

cal administration of penicillin. Arch.Neurol. & Psychiat., 58:39, 1947.

13. Teng, P. : The selection of antibiotics in

the treatment of purulent infections ofthe central nervous system with particu-

lar reference to their neurotoxicity by

the intracranial or intrathecal route. An-tibiotics Annual 1953-1954, p. 244.

14. Smith, D. T. : The disturbance of the nor-mal bacterial ecology by the administra-

lion of antibiotics with the development

of new clinical syndromes. Ann. Int.Med., 37:1135, 1952.

15. Turell, R., and Maynard, A. de L. : Ano-rectocolonic side-effects of antibiotic

therapy. J.A.M.A., 156:217, 1954.16. Manheim, S. D., and Alexander, R. M.:

Further observations on anorectal corn-plications following aureomycin, terra-mycin and chloromvcetin therapy. New

York J. Med., 54:231, 1954.

17. Dearing, W. H., and Heibman, F. R. : Mi-crocuccic (staphybococcic) enteritis as acomplication of antibiotic therapy: Itsresponse to erythromycin. Proc. StaffMeet., Mayo Clin., 28:121, 1953.

18. Newman, C. R. : Pseudomembranous en-

terocolitis and antibiotics. Ann. mt.Med., 45:409, 1956.

19. Lepper, M. H., et al. : Effect of large dosesof aurecmycin on human liver. Arch.mt. Med., 88:271, 1951.

20. Rutenberg, A. M., and Pinkes, S. : The he-patotoxicity of intravenous aureomycin.

New England J. Med., 247:797, 1952.21. Bridges, R. A., Berendes, H., and Good,

R. A. : Serious reactions to novobiocin.J. Pediat., 50:579, 1957.

22. Lewis, C. N., Putnam, L. E., Hendricks,

F. D., Kerlan, I., and Welch, H. : Chlor-amphenicol (Chloromycetin) in relationto blood dyscrasias with observations on

other drugs: A special survey. Antibiotics

& Chemother., 2:601, 1952.23. Saslaw, S., Doan, C. A., and Schafer, R. L.:

Studies on prolonged administration of

chboramphenicol in monkeys. AntibioticsAnnual 1954-1955, p. 383.

24. Payne, H. M., Bullock, W., Hackney, R. L.,McKnight, H. V., and Syphax, G. B.:

The protracted intramuscular use ofchloramphenicol. Antibiotics Annual1956-1957, p. 359.

25. Woolington, S. S., Adler, S. J., and Bower,A. G. : Five years’ experience with chlor-

amphenicol. Antibiotics Annual 1956-

1957, p. 365.

26. Carr, D. T., Pfuetze, K. H., Brown, H. A.,

Douglass, B. E., and Karlson, A. G.:Neomycin in clinical tuberculosis. Am.Rev. Tuberc., 63:427, 1951.

27. Powell, L. W., Jr., and Hooker, J. W.:Neomycin nephropathy. J.A.M.A., 160:

557, 1956.

28. Longacre, A. B., and Waters, R. : Paren-teral bacitracin in surgical infections.

Am. J. Surg., 81:599, 1951.

29. Kagan, B. M., Krevsky, D., Milzer, A., and

Locke, M. : Polymyxin B and polymyxinE. : Clinical and laboratory studies. J.Lab. & Clin. Med., 37:402, 1951.

30. McDermott, W. : Toxicity of streptomycin.

Am. J. Med., 2:491, 1947.31. O’Connor, J. B., Christie, F. J., and How-

lett, K. S., Jr. : Neurotoxicity of dihydro-

streptomycin; effects of longer-term ther-apy. Am. Rev. Tuberc., 63:312, 1951.

32. Heck, W. E., Lynch, W. J., and Graves,H. L. : A controlled comparison of theeighth nerve toxicity of streptomycin


SOME COMPLICATIONS OF TRANSFUSION, ENDOCRINETHERAPY AND OXYGEN ADMINISTRATION

By A. L. Chute, M.D., F.R.C.P.(C)Department of Pediatrics, University of Toronto, and the Hospital for Sick Children, Toronto

than withdrawal.

Due to the impetus given by life-saving


ADDRESS: 555 University Avenue, Toronto, Ontario, Canada.

and dihydrostreptomycin. Ann. Otob.Rhin. & Laryng., 62:101, 1953.

33. Winston, J. : Clinical problems pertainingto neurotoxicity of streptomycin groupof drugs. Arch. Otolaryng., 58:55, 1953.

34. Jongkees, L. B. W., and Hulk, J. : The ac-

tion of streptomycin on vestibular func-tion. Acta oto-laryng., 38:225, 1950.

35. Kern, A. R., and Wimberbey, N. A., Jr.:

Penicillin reactions: Their nature, grow-ing importance, recognition, manage-ment and prevention. Am. J. M. Sc.,226:357, 1953.

36. Welch, H., Lewis, C. N., Putnam, L. E.,and Randall, W. A. : A study of the

sensitizing potential of novobiocin. An-tibiotic Med., 3:27, 1956.

37. Breese, B. B., Disney, F. A., and Talpey,W. B. : Novobiocin in the treatment of

beta-hemolytic streptococcal infections

in children. Antibiotic Med., 4:347,1957.

38. Brown, E. A. : The prevention of anaphy-lactic reactions to penicillin (Editorial).Antibiotic Med., 1:439, 1955.

39. Kagan, B. M., Nierenberg, M., Goldberg,D., and Milzer, A. : Studies of penicillinin pediatrics. III. Procaine penicillin G

COMPLICATIONS OF TRANSFUSION

I N NO FIELD has medical opinion reversed

itself so completely as in that of blood

letting versus blood replacement.

A short time ago while visiting the re-

constructed colonial town of Williamsburg,

one saw the tools of the old barber sur-

geons. A copy of a manuscript on the wall

stated that George Washington was bled

on several occasions during his terminal ill-

ness, without seeming benefit.

In this paper, I would like to emphasize

some of the ills of blood replacement rather

in sesame oil, in peanut oil with 2%aluminum monostearate and in water

with sodium carboxymethylcellulose. PE-

DIATRICS, 5:664, 1950.40. Welch, H., Lewis, C. N., Kerlan, I., and

Putnam, L. E. : Acute anaphylactoid re-actions attributable to penicillin. Anti-biotics & Chemother., 3:891, 1953.

41. Ruskin, E. R. : Penicillin anaphylaxis fol-lowing percutaneous absorption. NewYork J. Med., 54:1519, 1954.

42. A Report from the Ministry of Health:Sensitization of nursing staffs to anti-

biotics. Bnit. M. J., 2:39, 1953.43. Rogers, D. E. : The current problem of

staphylococcal infections. Ann. Int.Med., 45:748, 1956.

44. Weinstein, L., Goldfield, M., and Chang,T. : Infections occurring during chemo-therapy; a study of their frequency, typeand predisposing factors. New EnglandJ. Med., 251:247, 1954.

45. Weinstein, L. : The chemoprophylaxis of in-

fection. Ann Int. Med., 43:287, 1955.

46. Nolen, W. A., and Dille, D. E. : Use andabuse of antibiotics in a small commu-mty. New England J. Med., 257:33,1957.

transfusions during the war, blood transfu-

sion has become universally available in all

parts of the country. This has not proved an

unmixed blessing, however, for the dangers

associated with blood transfusion have also

been greatly multiplied thereby.

The factors which give rise to these dan-

gers are as follows : 1) those associated with

donor; 2) those associated with stored

blood; 3) those associated with act of trans-

fusion; 4) those associated with recipient.

1 . Factors Associated with Donor

1. Homologous serum jaundice.

2. Allergic reactions.


1958;22;164Pediatrics T. E. Roy


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American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397. American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1958 by thebeen published continuously since 1948. Pediatrics is owned, published, and trademarked by the Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has


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