1121

bodies in antisera to H.C.G. The amount of labelled H.C.G.
in the aggregate is inversely proportional to the H.c.G. or
L.H. in the sample. The method does not distinguish
between L.H. and H.C.G., but measures L.H. alone in normal
non-pregnant subjects. Levels of H.C.G. as low as 0.001
I.U. per ml. have been detected and this sensitivity is
valuable in the measurement of H.C.G. produced by
trophoblastic tumours. It has been suggested that
immunoassays for H.C.G. and L.H. should give values
which are numerically similar to those given by bioassay;
but there are reasons why these two approaches would be
expected to give different estimates for H.c.G. and a useful
comparison of estimates for L.H. in body fluids is not yet
possible because of the limitations of existing bioassay
methods.
We thank the British Empire Cancer Campaign, the Medical
Research Council, the Wellcome trust, and Tenovus for financial
assistance; the board of governors of Charing Cross Hospital for their
generous support; and Dr. Anne Hartree and the National Institutes
of Health, Bethesda, Maryland, for supplies of L.H. preparations.
Requests for reprints should be addressed to Dr. K. D. Bagshawe,
Edgar Laboratory, Fulham Hospital, London W.6.
REFERENCES
Albert, A., Kobi, J., Leiferman, J., Derner, I. (1961) J. clin. Endocr. 21, 1.
Bell, E. T., Loraine, J. A. (1966) Lancet i, 626.
Mukerji, S., Loraine, J. A. (1964) J. Endocr. 28, 321.
—
The following four cases, exhibiting the ill effects of
cathartic " addiction ", are of interest partly because of
the varied clinical presentations but also because of the
great difficulty in reaching a correct diagnosis, which was
largely resolved when it was realised that the patients were
taking cathartics.
Case-reports
Case1
A woman of 50, first seen in 1952 complaining of constipa-
tion. Physical examination was negative. Barium enema
showed the colon to be dilated, lacking in haustrations,
generally atonic but with occasional tight ring-like contractions;
sigmoidoscopy showed a pale mucosa. It was noted that she
took laxatives but no significance was attached to the fact. The
surgeon and radiologist were baffled by the remarkable appear-
ance of the colon and finally decided that it might be due to a
" burnt-out colitis ".
In 1962 she again came to the hospital complaining of
excessive fatigue and diarrhoea. Sigmoidoscopy showed a pale,

Borth, R., Menzi, A. (1964) Acta. endocr., Copenh. suppl. 90, p. 17.
Brown, J. B., Loraine, J. A. (1955) J. Endocr. 13, p ii.
Butt, W. R., Cunningham, F. J., Hartree, A. S. (1964) Proc. R. Soc. Med.
57, 107.
Got, R., Bourfillon, R. (1960) Biochim. biophys. Acta 39, 241.
Greenwood, F. C., Hunter, W. M., Glover, J. S. (1963) Biochem. J. 89, 114.
Greep, R. O., van Dyke, H. B., Chow, B. F. (1942) Endocrinology, 30, 635.
Hobson, B., Wide, L. (1964) Acta endocr., Copenh. 46, 632.
Hales, C. N., Randle, P. J. (1963) Biochem. J. 88, 137.
Hutchinson, J. S. M., Worden, J. M., Prunty, F. T. G. (1965) J. Endocr.
32, 237.
Imura, H., Sparks, L. L., Grodsky, G. M., Forsham, P. H. (1965) J. clin.
Endocr. 25, 1361.
Johnsen, S. G. (1958) Acta endocr., Copenh. 28, 69.
Klinefelter, H. F., Albright, F., Grinswold, G. C. (1943) J. clin. Endocr.
3, 529.
Levin, L., Tyndale, H. H. (1937) Endocrinology, 21, 619.
Loraine, J. A. (1950) J. Endocr. 6, 319.
(1957) Acta endocr., Copenh. suppl. no. 31, p. 75.
—

(1958) The Clinical Application of Hormone Assay. Edinburgh.

—

— Bell, E. T., Harkness, R. A., Mears, E., Jackson, M. C. N. (1965) Fig. 1-Two typical pseudostrictures (case 1).
Acta endocr., Copenh. 50, 15.
Brown, J. B. (1956) J. Endocr. 13, 1.
—

redematous looking mucosa which did not bleed easily. A

—
(1959) ibid. 18, 77.
—

— Mackay, M. A. (1961) ibid. 22, 277. barium enema (fig. 1) showed identical appearances to ten
R.
Mellinger, C., Mansour, J. A., Smith, R. W. (1963) Acta endocr., Copenh.
42, 214. years before but this time the radiologist suggested she might
Parlow, A. F. (1958) Fedn Proc. Fedn Am. Socs exp. Biol. 17, 402. have the so-called " cathartic colon". Questioning then
Rosemberg, E., Solod, E. A., Albert, A. (1964) J. clin. Endocr. 24, 714. revealed that she had taken 2-3 tablets of a proprietary vegetable
Schmidt-Elmendorff, H., Loraine, J. A. (1962) J. Endocr. 23, 413.
Wide, L. (1962) Acta endocr., Copenh. suppl. 70. laxative every night for the past 35 years. She stopped taking
Wilde, C. E., Bagshawe, K. D. (1965) Ciba Fdn. Study Grps, 22, 46. the vegetable laxatives for a time but soon began again because
Orr, A. H., Bagshawe, K. D. (1965) Nature, Lond. 205, 191.
—

(1966) J. Endocr. (in the press).

— — —
CATHARTIC COLON
M. D. RAWSON
M.B. Leeds, M.R.C.P., F.F.R.
SENIOR REGISTRAR, UNIVERSITY DEPARTMENT OF NEUROLOGY,
MANCHESTER ROYAL INFIRMARY
THE widespread use of cathartic drugs is an index, not
so much of a real need for them, but of the belief that to
miss a bowel movement is likely to have serious conse-
quences. It has been suggested (Lancet 1962a) that
" perhaps the concept of ’inner cleanliness ’ is dying as
calmer iatric influences prevail " and (Lancet 1962b)
that vegetable cathartics containing such irritants as
podophyllin, jalap, and colocynth should have no place
in modern medical treatment. The British Medical
Journal (1961) drew attention to the dangers of purgatives.
In spite of all this, proprietary cathartics are still widely
advertised to the public; and many people believe in the
necessity of a daily bowel motion of a certain consistency
and colour, in order to maintain health.
she felt bloated and uncomfortable.
Case 2
A 57-year-old woman who was first seen in 1957 complaining
of abdominal distension, pain in the lower abdomen, and
constipation for 15 years. The symptoms were relieved for a
few hours after her bowel moved. Physical examination was
normal apart from gaseous abdominal distension. Rectal
examination was negative. A barium enema showed a dilated
colon but no organic lesion was seen.
In 1960 she was admitted to hospital with severe thirst.
Diabetes insipidus was diagnosed but urine output was normal
and it was soon evident that she was having copious watery
motions. Sigmoidoscopy and abdominal examination by a
surgeon were negative. It was felt that she might have
" "
pancreatic insufficiency and she was put on pancreatin. The
diarrhoea diminished. Again the question of purgatives was not
raised.
Later in 1960 she was readmitted to hospital with inter-
mittent distension of the abdomen and copious, liquid diarrhoea.
A laparotomy was performed and the surgeon found con-
siderable distension of all the colon. The wall was much
thickened but the colon was freely mobile and there was no
obstruction. It was concluded that the distension of the colon
might be due to " an imbalance of her parasympathetic and
sympathetic nerve mechanisms."
1122
Fig. 2-Barium enema showing loss of haustrations and typical
pseudo stricture in transverse colon (case 2).
She then developed hxmaturia, oliguria, and oedema of the
face and legs. Urine contained red blood-cells. " Acute
nephritis " was diagnosed and the hxmaturia and cedema
cleared in 3 weeks. She remained extremely weak for several
months.
Prof. J. C. Goligher saw her in 1962 and performed a
sigmoidoscopy which showed a pale oedematous mucosa. A
barium enema (fig. 2) showed distension, loss of normal
haustrations, and areas of tight ring-like constrictions which
were not permanent. The terminal ileum was also tube-like
and rigid. Then on direct questioning she admitted that she
had taken 2-3 vegetable laxative tablets almost every day for
15 years and was accustomed to passing five or six watery
motions a day. It was not possible to wean her off the vegetable
laxative.
Comment.-This patient had severe illnesses and a laparotomy
because it was not realised that she had been taking vegetable
cathartics daily for 15 years.
Case 3
A woman, aged 74. In 1926 she had had an anal stricture
after an operation for a rectal prolapse, and took vegetable
laxatives to keep her motions fluid. At times she had a curious
thirst which could not be properly satisfied by water. She
remained in reasonable health until 1957, when she became
very weak and completely lost the use of her limbs. This
t’ig. :i—Uanum cnc’ma shoeing abnormal colon, vsith loss ofr
haustrations, abnormal terminal ileum, and pseudostricture,
(case 3).
"
diagnosed as a stroke ", but she recovered spontaneously in
5 weeks. In 1958 she again became very weak and was admitted
to hospital. On examination muscular power was reduced
generally and her abdomen was moderately distended; rectal
examination showed a tight anal stricture. Blood-pressure was
85/55 mm. Hg. Investigations showed that she had hypo-
kalaemia (serum-potassium 2 mEq. per litre). Her urine
showed red blood-cells, granular casts and a moderate amount
of albumen. Barium enema showed an atonic colon and
abnormal ileocsecal region (fig. 3). This was not recognised as
a " cathartic colon " and was thought to be either Crohn’s
disease or tuberculosis of the ileocaecal region.
Over the next few years she had variable muscular weakness
but in 1961 she was again admitted to hospital with attacks of
stiffness of the fingers and generalised muscular weakness. The
history suggested tetany (serum-calcium was 7 mg. per 100 ml.)
and she also had low serum-potassium (2-4 mEq. per 100 ml.).
It was still not realised that the profuse watery diarrhoea was
due to taking cathartics.
Later in 1961 she was admitted to a metabolic ward where it
was found that she had a copious watery diarrhoea, steatorrhoea
(93 g. of fat in 6-day stool), hypokalxmia (serum-potassium 2-4
mEq. per 100 ml.), hypocalcxmia (plasma-calcium 7-9 mg.
per 100 ml.). Rectal biopsy showed cedema of the mucosa with
a slight increase in leucocytes, mainly plasma cells towards one
extremity of the lamina propria. The muscularis mucosa
showed slight lymphoid infiltration. There was no sign of
ulceration or new growth. A barium enema showed a typical
" cathartic colon " (fig. 3).
Comment.-This patient began taking vegetable cathartics
following anoperation for rectal prolapse and a tight anal
stricture developed. The history of chronic purgation was
overlooked until late in the illness. Her episodes of severe
muscular weakness were presumably due to hypokalsmia.
Most of the dietary potassium was lost in the voluminous stool.
The hypocalcsemia was considered to be secondary to the
steatorrhoea. The terminal ileum was shown to be abnormal
on barium studies and this may have caused the steatorrhcea.
She could not stop taking cathartics.
Case 4
A 57-year-old woman. In 1956 she began to complain of
tiredness and exhaustion. At the same time she had clearly
defined tetanic cramps in the hands and feet, progressive loss
of weight (two stones), and thirst which was not completely
satisfied by water. In August, 1956, she was investigated in
"
hospitaland was diagnosed as potassium-losing nephritis
A renal calculus was demonstrated on X-ray.
was In March, 1957, she had profound muscle weakness and
cramps and was virtually unable to move for 3 weeks. Spon-
taneous improvement occurred after 3 weeks. In 1958 she was
again admitted to hospital and on routine questioning about
her bowels she said that she took an occasional vegetable
laxative but she had taken none for 6 months. On examination
she looked ill. Her blood-pressure was 90/60 mm. Hg., she
was hiccoughing and her skin was dry. The abdomen was
slightly distended. Sigmoidoscopy showed a pale mucosa with
no ulceration. A barium enema showed an initially dilated
and atonic bowel. Later the typical ring-contractions
appeared. The terminal ileum was also dilated and was
clearly abnormal.
Metabolic studies were very detailed but the main findings
were: severe sodium deficiency (serum-sodium 125 mEq. per
litre), severe potassium deficiency (serum-potassium 2-2 mEq.
per litre), alkalosis (blood pH 7-55), and nitrogen retention
(blood-urea 120 mg. per 100 ml.).
Comment.-This patient claimed to be constipated and denied
taking laxatives. On admission to hospital she was found to
have profuse watery diarrhoea, which contained nearly all her
dietary electrolyte intake. She was disturbed psychologically
.
and her physician suspected that she was taking laxatives
surreptitiously. Her handbag was X-rayed and a bottle

containing laxative tablets was identified. Her diarrhoea
stopped abruptly when the physician made it clear that he
knew she was taking laxatives whilst in hospital. Her progress
was then good and all the biochemical findings reverted to
normal.
All four women took the same proprietary vegetable
laxative (Burroughs Wellcome) (dose, 1-3 tablets) which
contained:
Discussion
These cases are presented in some detail to illustrate
the difficulties encountered in diagnosis. Several wrong
diagnoses were made before it was realised that the
symptoms were being caused by cathartics.
Case l.-Consultant surgeon and radiologist decided the
appearance of the colon must be due to " burnt-out
colitis ".
Case 2.-Consultant physician, surgeon, and radiologist
failed to diagnose correctly. The following diagnoses
were suggested: ? acute nephritis; diabetes insipidus
(severe thirst); neurasthenia (weakness); pancreatic
insufficiency; " an imbalance between the sympathetic
and the parasympathetic nerve systems akin to pseudo-
cyesis " (abdominal distension); or ulcerative colitis (she
had a laparotomy and colectomy was even considered).
Case 3.-Several physicians saw her and did not realise
she was " addicted to cathartics. Several wrong diag-
noses were made: "stroke"; neurasthenia; Addison’s
disease; Crohn’s disease or ileocxcal tuberculosis.
Case 4.-Diagnosed as potassium-losing pyelonephritis,
Conn’s syndrome, or Addison’s disease.
The diagnostic difficulties are partly due to the failure
of the patients to volunteer the information that they are
taking laxatives. Sometimes they deny taking them when
all the evidence suggests that they are. This clandestine
use of laxatives has been noted by Grauwels (1962) and
Schwartz and Relman (1953) found that one patient, a
young woman, only disclosed that she was taking laxatives
after 3 weeks of a careful balance-study. The two patients
described by French et al. (1956) were even more devious:
both had diarrhoea and during routine testing of the stools
it was found by chance that phenolphthalein was present
in the stools. When taxed, both denied taking laxatives,
but phenolphthalein subsequently disappeared from the
stools. de Graeff (1961) pointed out that these patients
are usually women, with strong psychoneurotic trends
and food fads.
All four patients had abnormal barium-enema appear-
ances. Heilbrun (1943) first described the X-ray changes
in the colon associated with prolonged cathartic abuse.
Later Jewel and Kline (1954) and Heilbrun and Bernstein
(1955), reported a further nine patients. Plum et al. (1960)
analysed the X-rays of patients with " cathartic colon "
seen at the Mayo Clinic. The features were: changes first
seen on the right side of the colon later involving entire
solon and sometimes the terminal ileum; absence of
normal haustral markings; a smooth wall with no irregu-
larity ; no stiffening or thickening of the bowel (on the
contrary the colon was distensible); smooth tapering
1123
contractions appeared which could be interpreted as
strictures but when observed they slowly disappeared and
reappeared in another part of the colon. These pseudo-
strictures seem absolutely typical of this condition and
have great diagnostic value. All my patients had these
X-ray appearances and some of the X-rays are shown. It
is interesting to speculate on how the interesting radiologi-
cal appearances of the cathartic colon are produced. Good-
man and Gilman (1965) state that the cathartic resins act
as irritants to the small intestine causing hypermobility
and profuse watery stools; but the colon must also be
stimulated because of the X-ray appearances seen after
years of cathartic abuse. Presumably the daily un-
physiological stimulation of the bowel by irritant cathartic
resins over many years leads to atony of the bowel. The
unusual pseudostrictures must represent a considerable
neuromuscular disturbance of the colon because they are
quite unlike any normal physiological waves.
The radiological appearances may be confused with
ulcerative colitis. Points of difference are the ragged
mucosal surface, true strictures, and shortening of the
colon seen in ulcerative colitis. If the colon is dilated in
ulcerative colitis the patient is usually seriously ill
(Korelitz and Janowitz 1960), whereas the dilated
cathartic colon is compatible with good health provided
that serum-electrolyte levels are normal. Sigmoidoscopy
also helps to differentiate the two conditions. The red,
bleeding, ulcerated mucosa of colitis is quite different to
the pale, oedematous mucosa seen in the cathartic colon.
Rectal biopsy was done in case 3 and this only showed
oedema of the mucosa with slight plasma cell infiltration
of the lamina propria, whereas in ulcerative colitis histology
of the mucosa often shows ulceration, fibrosis and heavy
infiltration with polymorphs.
Two of my patients (3 and 4) had severe hypokalxmia,
and three patients also complained of a curious thirst
which was not fully satisfied by water. Mahler and
Stanbury (1956) noted that thirst is a characteristic
symptom of severe potassium deficiency and could be a
valuable pointer to the diagnosis. Hypokalasmia as a
result of cathartic abuse was first emphasised by Schwartz
et al. (1953) in America, and Martensson (1953) in Scandi-
navia. In the U.K., Houghton and Pears (1958) first drew
attention to the serious affects that cathartic overdosage
can have. The hypokalaemia can be accounted for by the
loss of potassium in the copious watery motions and by
the inadequate diet, which many of these patients have.
Three of my patients had evidence of renal damage a
complication noted by de Graeff and Schurrs (1960) and
Linquette et al. (1964). Metabolic alkalosis, initial
alkaluria, and low urinary citrate excretion in potassium
depletion may cause stone formation and haematuria
(Stanbury 1958). Cases 2, 3, and 4 had hxmaturia and
case 4 also had a renal calculus. The functional and
structural renal defects which may accompany severe
potassium depletion may cause permanent renal damage.
Two patients had tetany and one certainly had steatorrhcea
(case 3), and the other (case 4) had severe metabolic
alkalosis. Steatorrhoea is a complication of cathartic abuse
presumably because of the small-bowel abnormality some-
times seen on barium studies. Both French et al. (1956)
and Coghill et al. (1959) found moderate steatorrhoea in
their patients. Case 3 had hypocalcxmia possibly asso-
ciated with her steatorrhoea. Her serum-calcium was
restored to normal by supplementing calcium in the diet.
In this connection it is interesting to note that Meulen-
1124

gracht (1939) reported " osteomalacia " of the spinal
column from excessive laxative taking. Permanent mic-
roscopic changes and secondary pyelonephritis may occur
in the kidney, possibly as a result of potassium depletion
(de Graeff 1961). It is not clear whether the neuromuscu-
lar disorder of the colon and small bowel can return to
normal when laxatives are stopped. Case 2 was found to
have an extremely thickened wall to her colon at lapar-
otomy, but this may have been due to oedema. The rectal
biopsy on case 3 only showed oedema with very slight
cellular infiltration. Heilbrun (1943) described a patient
with an obvious " cathartic colon " who stopped taking
the laxative for 18 months and the X-ray appearance
of the colon improved; but she then resumed the
habit.
The prognosis for giving up the cathartic habit once it
is firmly entrenched is not good. Three of my patients
were unable to stop taking laxatives because they felt
" its reversal should result in reduced whole-blood viscosity
constipated ", " bloated ", " distended ", or had other
abdominal discomfort. One patient promised to give up
the habit but was not followed up. Both Houghton and
Pears (1958) and Conte et al. (1960) had patients who took
laxatives surreptitiously after the drugs had been with-
drawn by the physician.
Patients with illness caused by the abuse of cathartics
may present in many different clinics. To avoid mis-
diagnosis, it should be remembered that the most import-
ant thing in arriving at a diagnosis is to take a detailed
history and determine the serum-potassium (British
Medical Journal 1961).
EFFECTS OF DEXTRAN 40
ON ERYTHROCYTE AGGREGATION
J. ENGESET A. L. STALKER
M.B. Aberd. M.D. Aberd.
RESEARCH ASSISTANT IN SURGERY READER IN PATHOLOGY
N. A. MATHESON
Ch.M. Aberd., F.R.C.S., F.R.C.S.E.
SENIOR LECTURER IN SURGERY
UNIVERSITY OF ABERDEEN
DEXTRAN 40 (low-molecular-weight dextran,’Rheo-
macrodex ’), a dextran fraction with an average molecular
weight of 40,000, is claimed to improve blood-flow in the
microvasculature (Gelin and Ingelman 1961). Any such
effect is largely dependent on the hypothesis that dextran
40 prevents or reverses intravascular erythrocyte aggre-
gation, and since the thixotropic properties of blood are
increased by erythrocyte aggregation (Dintenfass 1962),
and improved tissue perfusion. Further, although the
clinical and pathological significance of erythrocyte aggre-
gation in man is not certain, there is evidence of its harmful
nature in animals (Stalker 1961). Therefore, counter-
action of erythrocyte aggregation may be therapeutically
important; but in the absence of a method of measuring
the aggregation objectively the evidence for its prevention
or reversal by dextran 40 is largely indirect.
Thorsen and Hint (1950) showed in a series of in-vitro
experiments that dextrans of low molecular weight

Summary
"
Four patients, eventually found to be addicted " to
the taking of vegetable cathartics, are reported. Diagnosis
of " cathartic colon " was difficult and was complicated
by the fact that such patients tend to conceal or deny
their addiction. The X-ray appearances are fairly charac-
teristic, however, and can be differentiated from those of
ulcerative colitis. The most reliable diagnostic aids are to
take a complete history and to determine the serum-
potassium.
I thank Prof. J. C. Goligher and Prof. S. W. Stanbury for their
advice and help in the preparation of this paper.
Requests for reprints should be addressed to M. D. R., Manchester
Royal Infirmary, Oxford Road, Manchester 13.
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British Medical Journal (1961) ii, 1694.
Coghill, N. F., McAllen, P. M., Edwards, F. (1959) Br. med. J. i, 14.
Conte, M., Malvezin, J., Fouet, P., Goiffon, B. (1960) Archs Mal. Appar.
dig. 49, 956.
de Graeff, J. (1961) Ned. Tijdschr. Geneesk. 105, 2000.
Schurrs, M. A. M. (1960) Acta. med. scand. 166, 407.
—

French, J. M., Gaddie, R., Smith, N. (1956) Lancet, i, 551.

Goodman, L. S., Gilman, A. (1965) The Pharmacological Basis of Thera-
peutics; p. 1017.
Grauwels, J. (1962) Acta. gastroent. belg. 25, 858.
Heilbrun, N. (1943) Radiology, 41, 486.
—

Bernstein, C. (1955) ibid. 65, 549.

Houghton, B. J., Pears, M. A. (1958) Br. med. J. i, 1328.
Jewel, F. C., Kline, J. R. (1954) Radiology, 62, 368.
Korelitz, B. I., Janowitz, H. D. (1960) Ann. intern. Med. 53, 153. Fig. 1-Illustration of degrees of aggregation observed. Fresh
Lancet (1962a) i, 1010. preparations (reduced by ’/2 from 700).
—

(1962b) ii, 1098.
Linquette, M., Biserte, G., Gasnaut, J. P. (1964) Lille. méd. 9, 46.
Mahler, R. F., Stanbury, S. W. (1956) Q. Jl Med. 25, 21.
Mårtensson, J. (1953) Nord. Med. 49, 56.
Meulengracht, E. (1939) Acta. med. scand., 101, 187.
Plum, G. E., Weber, H. M., Sauer, W. G. (1960) Am. J. Roentg. 83,
919.
Schwartz, W. B., Relman, A. S. J. (1953) J. clin. Invest. 32, 258.
Stanbury, S. W. (1958) Adv. intern. Med. 9, 231.
(a) Grade .—Erythrocytes in short, loose rouleaux. Appearances
less than this were graded 0.
(b) Grade 2.-Erythrocytes in longer and more closely packed
rouleaux with occasional branching.
(c) Grade 3.-Rouleaux large and adherent to one another at all
angles to form irregular loose masses.
(d) Grade 4.-Masses more compact and rounded. Cell borders
less distinct and origin from rouleaux less readily seen.