MARCH 8, 1952 CORONARY DISEASE IN DOCTORS
merely to improving diagnosis in the one group com-
pared with the other, since fatal and non-fatal attacks
have equally increased. Beyond those tentatively
drawn conclusions the authors cannot, and wisely
do not, attempt to go. They emphasize instead the
importance of further work, and its extension, beyond
the records of the particular assurance society to
which their study was confined, to the whole medical
profession. It should be profitable, they suggest, not
only to explore the antecedents of coronary heart
disease among doctors and to expand the clinical
picture of it, but also, through the field survey
approach, to investigate the possible associations and
relationships of the disease. For "Physician, heal
thyself " we must perhaps substitute to-day the less
euphonious " Physicians, epidemiologically survey
yourselves." Dr. Morris and his colleagues have
made a good start, and it is to be hoped that with
the co-operation of the profession the Medical
Research Council's Social Medicine Research Unit
will be able to expand its work and carry out
systematic studies on a large scale, with the aim of
preventing a disease which numbers so many doctors
among its victims.
SUPERINFECTIONS DURING ANTIBIOTIC
TREATMENT
The term "superinfection" has come into use to
describe fresh complicating infections arising during
antibiotic therapy. An initial response to treatment
marks the overcoming of the original infection, to be
succeeded by a worsening of the patient's condition,
accompanied by the appearance of bacteria resistant
to the drug which were not found before. These bac-
teria may be presumed to have been present in small
numbers before treatment began and to have found
an opportunity to multiply in the circumstances so
produced. The obvious circumstance resulting from
antibiotic treatment, apart from action on any specific
pathogen, is the suppression of the general flora of
certain areas of the body. Penicillin exerts this sup-
pressive action mainly in the mouth, owing to' its
excretion in the saliva, and it is well recognized that
in patients receiving heavy doses of this drug strepto-
cocci and other bacteria in the mouth are largely re-
placed by coliform bacilli. Superinfections during
penicillin treatment are for the same reason chiefly
liable to involve the air passages. The newer anti-
1 J. Lab. cln. Med., 1951 37, 394.
S British MedilJournal, 1951,1, 1196.
8 lbid 1951,1, 205.
*J. ict. DI&., 1949, , 268.
5 Arch. Intern. Med., 1951, 88,729.
MEDICALJOURNAL 537
biotics affect in this way not merely the mouth but
the entire alimentary tract, since they are not only
administered by this route but also incompletely
absorbed. From studies such as those of Bierman
and Jawetz' it is known that in a patient taking
" aureomycin" (chloramphenicol has a less pro-
nounced effect) most of the normal intestinal flora
are suppressed for as long as treatment continues,
but to some extent replaced by Pseudomonas, yeasts,
and staphylococci resistant to the drug.
In view of this much more widespread interference
with the normal bacterial population of the body it
is not surprising that superinfections occurring during
the course of or after treatment with these newer
drugs have excited much more attention. They are
in fact quite common during prolonged treatment,
taking the form of a glossitis or an affection of the
anal region caused by Candida (Monilia) albicans.
This yeast-like fungus is highly resistant to all known
chemotherapeutic agents. It was because such infec-
tions may take a more serious form, spreading from
the.mouth to the bronchi and lungs, that the Council
on Pharmacy and Chemistry of the American Medical
Association decided last year that a warning state-
ment must be printed on the packages of these drugs
in the U.S.A., a somewhat startling procedure to
which reference was made at the time in these
columns.2 Our comparative inexperience of such
conditions in this country is due simply to the scarcity
here of some of the drugs causing them, although
minor manifestations such as glossitis,have become
familiar. What may be an example, and an unusual
one, of such a superinfection is reported by Drs. J. D.
Abbott, H. V. J. Fernando, K. Gurling, and B. W.
Meade on page 523. A patient with post-influenzal
bronchopneumonia was found to have Bact. coli and
Candida albicans in her sputum: it is not stated that
she had had treatment with penicillin during the
preceding three weeks of the illness, although such
a finding would lead one to suppose it. Despite treat-
ment with penicillin, streptomycim, and chlorampheni-
col she died, and was found at necropsy to have cavi-
tating pulmonary aspergillosis, although the presence
also of C. albicans in the lung cavities was confirmed.
It is of course possible that the Aspergillus infection
existed before antibiotics were given and would in
any case have been fatal, but when such a condition
makes its appearance during the administration of
drugs to which the causative organism is wholly insen-
sitive the suspicion that the treatment was doing posi-
tive harm cannot be put aside.
More information is needed about the mechanism
whereby resistant bacteria and fungi are enabled to
 538 MARCH 8, 1952 SUPERINFECTIONS DURING ANTIBIOTIC TREATMENT
proliferate and cause lesions during antibiotic therapy.
It may be that the suppression of the other flora of
the area either upsets a balance normally holding
them in check or simply provides them with more
pabulum. On the other hand, there is more than a
suspicion of positive stimulation to active growth by
the antibiotic itself. There is much evidence, recently
reviewed by Garrod3 in this Journal, that sublethal
concentrations of antibiotics as well as other noxious
agents accelerate the growth of bacteria, particularly
of resistant species. Directly bearing on the present
problem are the findings of Foley and Winter,4 who
showed that treatment with penicillin increased the
mortality from C. albicans infection in the chick
embryo. Pappenfort and Schnall,5 who reported
C. albicans infection in 16 patients treated with aureo-
mycin, also found that this drug stimulates the growth
of the organism in vitro. On the other hand, its
growth was also stimulated by solutions in which
aureomycin had been destroyed by heat or alkali, and
it was unaffected by a pure preparation intended for
parenteral injection. They therefore concluded that
an impurity was responsible for this effect. Evidently
the full truth of this matter is not yet known. Mean-
while we shall be well advised to remember that,
although the products of some species of fungi have
revolutionized therapeutics, there are other species
causing infections which are among the very few still
quite unaffected by any form of chemotherapy.
PSEUDOCYESIS
The woman who firmly but falsely believes herself
pregnant and in whom develop many of the symptoms
and some of the signs of pregnancy was known to
Hippocrates, while the clinical picture drawn by Sir
James Simpson in 18601 has never been bettered. The
reported cases of this medical curiosity total fewer than
500, but, as Simpson wrote, it is " of far more frequent
occurrence than the comparative silence of our text-
books on this malady would lead you to infer." This
is because most of the cases without very remarkable
features are not reported, the patient being merely
informed sooner or later that she is not pregnant with-
out any deeper search into the origin of her disorder.
After being thus dismissed she may go on to trouble
another doctor. Fried and his colleagues2 have recently
reported a series of 27 cases of pseudocyesis in which
the women, all but one of whom were childless, were
examined for endocrinological and psychiatric as well
as gynaecological defects. Spurious pregnancy is gener-
ally considered commoner in women near .the meno-
1 Clinica Lectures on Diseases of Women, 1872, Edinburgh, pp. 363-93.
2 J. Amer. med. Ass., 1951, 145, 1329.
3 Bivin, G. D., and Klinger, M. P., Pseudocyesls, 1937, Bloomington.
4 Brown, W. E., and Bradbury, J. T., Amner. J. Obstet. Gynec., 1947, 53, 749.
5 Eichner, E.,Goler, G. G.,Reed, J., and Gordon, M. B.,ibid., 1951,61,253.
MEnICBR JO,sNAH
pause, but Simpson often found it in younger women;
and the majority of Fried's patients were in the middle
twenties. These patients possess most of the usual
symptoms of pregnancy, but hypomenorrhoea is more
common than amenorrhoea. One of the most notable
features is the appearance of characteristic signs of
breast activity, including secretion, even in nulligravidae,
but in none of Fried's cases were the uterine or cervical
changes typical of true pregnancy. Yet women with
pseudocyesis pass superficial examination for pregnancy
with ease, chiefly because the possibility of the condi-
tion being spurious is not considered, and once the
diagnosis of pregnancy has been made the symptoms
flourish. In fact such women have been operated on
for supposed ectopic pregnancy and even for placenta
praevia. Moreover, the symptoms may continue for
years rather than months. Simpson relates that
Dupuytren, when asked by a lady who insisted she
had been pregnant for 14 years, what course she should
follow, answered that as the boy must be tolerably well
grown by that time the best thing the lady could do
was to swallow a tutor, that his education be not
neglected.
Fried regards pseudocyesis as a form of conversion
hysteria aild remarks on the frequency with which the
syndrome follows an emotional strain which the patient
believes can best be relieved by a pregnancy. A picture
of pseudo-pregnancy can sometimes be induced by the
administration of gonadotrophins, alone4 or in conjunc-
tion with oestrogen and progesterone5; but this differs
from pseudocyesis in that if the psychic factor and-pre-
disposition are not present the signs do not become
progressive, and there are no complaints of morning
sickness, enlargement of the abdomen, and "foetal
movements." Fried and his colleagues concluded that
the amenorrhoea in pseudocyesis is hyperhormonal,
whereas most forms of psychogenic amenorrhoea are
hypohormonal. In particular, evidence of progesterone
activity in most of the women seemed to point to per-
sistent corpus luteum function. This is not a new idea,
for Simpson wrote 90 years earlier, " Perhaps we would
find the corpora lutea tending to. simulate in their
development and growth the corpora lutea of preg-
nancy." But Fried goes further and propounds a hypo-
thesis that the basic mental conflict which appears best
solved by pregnancy affects the pituitary by way of the
hypothalamus. The reaction in the anterior pituitary,
he conjectures, leads to secretion of the luteotrophic
hormone at the expense of follicle-stimulating hormone,
and the result is persistent luteinic function in the ovary,
which could account for most of the clinical featiMes.
Whether this hypothesis is correct or not, it remains a
fact that, except in minor degrees of the syndrome,
merely telling the patient she is not pregnant is insuffi-
cient treatment, for either the woman is unconvinced
or, after an interval, further symptoms of pseudocyesis
bring her again to the doctor. Fried therefore recom-
mends psychotherapy, in order that the patient may
obtain an insight into her condition. The best evidence
of cure is the return of normal menstruation, the absence
of recurrence, and, best of all, a true pregnancy.