ACUTE INFECTIONS OF THE URINARY TRACT AND THE URETHRAL SYNDROME IN GENERAL PRACTICE.
- Medicine 04/1964; 43:91-130. · 4.23 Impact Factor
- The Australian journal of experimental biology and medical science 09/1958; 36(4):383-94.
- The Journal of Urology 10/1956; 76(3):270-5. · 3.70 Impact Factor
6 March 1965
Erythrodermic Skin Diseases-Fox et al.
has shown that this can stimulate non-shivering thermogenesis
calorigenic action of noradrenaline (Joy, 1962 ; Davis, 1963),
so that the slightly raised V.M.A. excretions found in this
study may be important. Shivering tends to disappear in the
cold-adapted subject, and this may explain why all except one
of our patients with a relative hypothermia failed to shiver.
These observations emphasize certain aspects of the manage-
ments of these patients.
Because of the reduced capacity to
thermoregulate, with its attendant dangers of hypothermia or
hyperthermia, body temperature must be accurately observed,
using a low-temperature thermometer when indicated.
usually require more clothes and a warmer room than the aver-
age person, and the risk of hypothermia is obviously greatest
during winter months and when they are treated at home, but
even in hospital care is needed during treatment periods. If the
patient develops a high body temperature steps should be taken
to reduce it in order to avoid an excessive increase in the cardiac
load. The aim should be to steer a course between the two
extremes and keep body temperature close to normal.
patient is seen to be shivering, complains of the cold, or has a
subnormal temperature, the room temperature or his clothing
should be promptly increased. The temperature at which he
becomes comfortable and shivering ceases should be recorded
and used as a guide to adjust his environment. Prompt treatment
of the skin condition, usually with corticosteroids, is the best
way of avoiding heart failure. The unexplained high mortality
of patients with erythrodermic skin diseases may in large part
be due to the haemodynamic and thermoregulatory problems
we have discussed.
also showed an increased
erythrodermic skin conditions have shown marked increases in
skin blood-flow equivalent to up to two-thirds of that seen in
normal subjects when fully vasodilated by heat ; there was a
considerable further increase in skin blood-flow when the body
temperature was raised.
All had a raised venous pressure with
hypervolaemia, and in two patients the cardiac output was
Body-temperature regulation was grossly disturbed.
out of five patients had either a fever or an elevation of the
set point for temperature regulation with body temperatures
below the fever level.
The capacity to thermoregulate is greatly
diminished in these patients, and hypothermia, which is an
inability of the skin blood-vessels to constrict fully.
The basal metabolic rate was raised considerably in 9 out
of 11 patients.
Radioactive iodine studies showed no evidence
of hyperthyroidism, but there was a slight increase in vanillyl
mandelic acid excretion.The hypermetabolism
mainly due to the abnormal skin metabolism, but the develop-
ment of non-shivering thermogenesis may also play a part.
is related to the high skin blood-flow and
Two of us (S. S. and J. M.) were supported by a grant from the
Medical Research Council.
Davis, T. R. A. (1963). Fed. Proc., 22, 777.
Fox, R. H., and Edholm, 0. G. (1963).
Goldsmith, R., Kidd, D. J., and Lewis, H. E. (1963).
(Lond.), 166, 548.
Fraser, R., Hobson, Q. J. G., Arnott, D. G., and Emery, E. W. (1953).
Quart. 7. Med., 22, 99.
Georges, R. J., and Whitby, L. G. (1964).
Hellon, R. F., and Clarke, R. S. J. (1959).
Joy, J. T. (1962). Physiologist, 5, 164.
Krook, G. (1960).
Acta derm.-venereol. (Stockh.), 40, 142.
Magnusson, B. (1960).
Ibid., 40, 161.
Pisano, J. J., Crout, J. R., and Abraham, D. (1962).
Robertson, J. D., and Reid, D. D. (1952). Lancet, 1, 940.
Robinson, S. (1949).
In Physiology of Heat Regulation and Science of
Clothing, edited by L. H. Newburgh, p. 206.
Sharpey-Schafer, E. P. (1955).
Shuster, S. (1963). Lancet, 1, 1338.
and Wilkinson, P. (1963).
Taylor, S. H., and Shillingford, J. P. (1959). Brit. Heart 7., 21, 497.
Wade, 0. L., and Bishop, J. M. (1962). In Cardiac Output and Regional
Blood Flow, p. 34.
Brit. med. Bull., 19, 110.
7. clin. Path., 17, 64.
Clin. Sci., 18, 1.
Clin. chim. Acta,
Brit. med. X., 1, 693.
Brit. 7. Derm., 75, 344.
Acute Infections of the Urinary Tract and the Urethral Syndrome
in General Practice
D. J. A. GALLAGHER,* M.B., M.MED.SC.; J. Z. MONTGOMERIEt M.B., M.R.A.C.P.;
J. D. K. NORTH,t M.B., D.PHIL., M.R.C.P., F.R.A.C.P.
Brit. med. J., 1965, 1, 622-626
What is the significance of single or repeated attacks, of infection
of the urinary tract ?
Our knowledge of these infections comes
mainly from studies of patients in hospitals (Wharton et al.,
1937; Jackson et al., 1957 ; Winberg and Barr, 1960) and from
post-mortem studies (Weiss and Parker, 1939 ; MacDonald
et al., 1957).
In contrast, most infections of the urinary tract
are diagnosed and treated at home by the general practitioner.
It is therefore important to examine the natural history of these
infections. We report a prospective study planned to investi-
gate the type of infection occurring in general practice, the
response to treatment with sulphafurazole (Gantrisin), and the
incidence of recurrent infections.
Urologists often see patients who complain of frequency and
dysuria without evidence of infection in the urine. The aetio-
attributed to an anxiety neurosis (Gray and Pingelton, 1956;
In this study we found that the urethral
syndrome was common in general practice; many patients
presenting with symptoms of infection had sterile urine.
assess the urethral syndrome these patients have been compared
with the remaining patients with definite infection in the urine
seen in the survey.
is obscure and has been
In New Zealand patients with acute infections in the urinary
tract are often treated with a sulphonamide by general practi-
tioners who do not have facilities for bacteriological examina-
tion of the urine.
This study was designed to determine the
deficiencies of treating patients in this way.
*Auckland Faculty, College of General Practitioners.
t Medical Unit, Auckland Hospital, Auckland, New Zealand.
Eight doctors' who had typical urban general practices took
part in the survey, which extended over eight months and was
designed to include all patients diagnosed on symptoms
having acute infections of the urinary tract.
have such infections were not included unless they developed
further symptoms during the trial.
symptoms and physical signs. A qualified nurse from Auckland
Hospital then visited the patient's home.
nurse prepared the vulva with chlorhexidine solution, and then
catheters in sterile containers were used to reduce to a minimum
the risk of introducing infection.
collected direct into a wide-mouthed sterile jar which was imme-
diately placed in a vacuum-flask packed with ice to reduce
The initial specimen of urine from each
female patient was collected by catheter because many of these
patients required prompt treatment.
mid-stream specimens by a strange
difficult in the patient's home, and without the opportunity of
repeating some of the specimens the results would have been
difficult to interpret.
Mid-stream specimens were obtained
from the male patients after cleansing the glans penis with
Catheter and mid-stream
specimens of urine were regarded
more than 10,000 bacteria per ml. of urine (Effers0e and Jensen,
All patients were treated with sulphafurazole, 1 g. four times
daily for 10 days, unless there was a contraindication to using
This treatment reduced further the chance of
bacteria introduced by the catheter causing an infection in the
Two weeks after the initial infection a mid-stream specimen
of urine was collected at the hospital.
specimens of urine were collected at six weeks and at three
months, when the patients were seen at the hospital by one
doctor. The following investigations were then carried out:
haemoglobin, erythrocyte sedimentation
clearance (Edwards and Whyte, 1958), 24-hour urinary protein,
and intravenous pyelogram.
cystograms were carried out.
Patients known to
For women, the
a catheter specimen of urine.
The urine specimen was
Adequate collection of
nurse would have been
one hour of collection
if there were
If indicated, cystoscopy or reflux
During eight months 135 patients were seen with symptoms
of an acute infection in the urinary tract. A specimen of urine
TABLE I.-Quantitative Bacterial Counts of Urine
No. of Patients
Bacterial Count (per ml.)
More than 100,000
Less than 10,000
Bacterial count not done*
*Urines examined outside normal laboratory hours.
was obtained from 130 patients, and the results from these
patients are reported below. Only 77 (59%) of the 130 patients
were found to have infected urine.
pared with the other 53 patients without infected urines.
These 77 patients are com-
Dr. D. G. Campbell, Dr. D. J. A. Gallagher, Dr. J. W. G. Gibb, Dr.
M. M. Harding, Dr. J. B. Lovell-Smith, Dr. M. Pearl, Dr. C. N.
Sorrell, and Dr. A. E. Walton-from the Auckland Faculty of the
College of General Practitioners.
Quantitative bacterial counts of all patients are given in Table
whom the urine was collected after normal laboratory hours.
Only 8 of the 77 infected patients had bacterial counts
between 10,000 and 100,000/ml.
without infection the bacterial count was zero.
Quantitative counts were not done in 13 patients from
In 41 of the 53 patients
Patients With Infected Urine
Age and Sex.-Of the 77 patients with infection 71 were
females and 6 males-a male-to-female ratio of 1: 12.
patients (five girls and two boys) were under 12 years of age.
Marriage and Pregnancy.-The marital status of the 35
women aged 16 to 40 with infected urine is shown in Table II.
Fourteen of these were either unmarried or nulliparous.
the remaining 21, who were either pregnant or multiparous,
8 gave a history of infection before their first pregnancy.
majority (22 out of 35) of these patients therefore had infec-
tion in the urine before their first pregnancy.
TABLE II.-Relation of Infection to Marriage and Pregnancy in Women
Aged 16 to 40
Abnormalities of Urinary Tract.-Obstruction or urinary
retention was an infrequent cause of infection and could have
been a contributory factor in only nine patients.
was infected after prostatectomy.
dilatation of the upper urinary tract was seen in one patient;
smaller cystoceles were found in four other patients. In three
patients the intravenous pyelogram showed unilateral pelvi-
ureteric narrowing with some obstruction. Two other patients
had small renal calculi without obstruction.
Reflux cystograms were carried out in four children who
had persistent or recurrent infections.
vesico-ureteric reflux; another had small diverticuli of the
bladder close to the lower ends of the ureters without vesico-
Bacteria Causing Initial Infections.-Bacteria isolated from
the urine of these patients are shown in Table III.
coli, which caused the infection in 60% of our patients, was
the predominant organism here as in most groups of patients
with urinary infections.
The isolation of coagulase-negative
staphylococci in the urine of 12 patients was unexpected.
normal subjects coagulase-negative staphylococci can be isolated
from the urethra in small numbers and may occur as a con-
taminant in urine (Guze and Beeson, 1956). The other findings
in the urine of these 12 patients suggest that these organisms
were causing definite infections.
100,000 organisms per ml. were found in 11 urines, significant
pyuria (more than
A gross cystocele with
One child showed
Bacterial counts greater than
cells per high-power
TABLE III.-Bacteria Causing Infection
No, of Patients
Paricolon organisms ...3
*11 patients had mixed infections.
6 March 1965
Infection of Urinary Tract-Gallagher et al.
Infection of Urinary Tract-Gallagher et al.
occurred in 10 urines, and proteinuria was found in seven
Response to Treatment.-A good response to sulphafurazole
occurred in 57 (79%) of 72 patients; the drug was contra-
indicated in the remaining patients.
urine did not clear with sulphafurazole, the infecting organism
was E. coli in nine ; Proteus in six; and Str. faecalis in one.
In vitro testing with disks indicated that 9 of the 16 organisms
were apparently sensitive to sulphafurazole.
Persisting or Recurrent Infections.-The rate of recurrence
after treatment was high.
Table IV gives details of 69 patients
with infections in whom follow-up was complete.
patients had persisting infections after treatment and nine others
had recurrent infections within three months-a total of 25
of the 69 patients with initial infection of the urine.
patients had mixed
Of the 16 patients whose
TABLE IV.-Persistent or Recurrent Infections in the Urinary Tract
Asymptomatic Bacteriuria.-Eleven patients had persisting or
recurrent infections without symptoms.
urine cleared spontaneously without further treatment.
otber patient developed symptoms, so that the prolonged asymp-
tomatic bacteriuria occurred in five patients.
Renal Function.-Renal damage, judged by impaired tests of
renal function or changes in the intravenous pyelogram, was
seen in very few patients.
The blood urea was normal in all
patients, and a creatinine clearance of less than 80 ml. a minute
was observed in only three patients.
pyelonephritis (Hodson, 1959) were present in the intravenous
pyelogram in five patients.
Lesser changes in the calices (Brod,
1956; Relman, 1960) and renal narrowing of the renal cortex
in the absence of caliceal distortion may or may not signify
renal damage from
narrowing without caliceal changes and four patients had cali-
ceal changes without extrinsic abdominal pressure.
suspicious or diagnostic of pyelonephritis.
In five of these the
Definite changes of
Patients Without Infected Urine
The results of these patients have been compared with those
with infected urine.
The interesting finding was the many
* INFECTED GROUP
* NON-INFECTED OR
similarities rather than the differences between the two groups
Initial Urine.-Minor abnormalities were found in the urine
in only 9 of the 53 patients without infection.
proteinuria occurred in eight patients and more than 5 white
cells per high-power field were found in the urine of seven.
Age and Sex.-The age incidence in the uninfected patients
was similar to that of those with infection, although there were
slightly more female patients aged 40 to 50 without infection
There were only three men whose urine was
without infection; two of these had frequency and nocturia due
to prostatic hypertrophy.
Marriage and Pregnancy.-There were 63 female patients in
the survey aged 16 to 40 years, of whom 43 % without infection
and 40% with infection were either unmarried or nulliparous
(Table II). The only difference between the two groups was a
higher incidence of pregnancy in patients without infection
compared with 20%).
Past History of Symptoms Related to the Urinary Tract.-
These symptoms were more common in patients without infec-
tion (79%, compared with 62%
urines) (Table V). For these previous episodes treatment had
been given to rather more than half the patients from both the
infected and the uninfected groups.
in the pattern of previous episodes in the two groups of
patients or in the time from the onset of the first attack.
A trace of
of patients with infected
There were no differences
TABLE V.-Previous History of Infections of the Urinary Tract
Symptoms previously treated
Previous urological investigation
Symptoms causing admission to
Symptoms.-These were recorded by the general practitioner
before the results of the urine were known, and showed only
minor differences between the infected and uninfected patients
(Table VI); fever, a history of haematuria, and dysuria were
significantly more common in patients with infection.
ment of symptoms is subjective and difficult. The degree of
certainty with which the diagnosis was made before bacterio-
logical examination of the urine is given in Table VII. Among
the uninfected patients there were fewer cases in which the
diagnosis appeared certain (19%) than among the infected
TABLE VI.-Presenting Symptoms
Loin pain .
Lower abdominal pain
TABLE VII.-Clinical Assessment of Diagnosis of Infection of the
Highly probable ..
6 March 1965
26- 31- 36- 41- 46-
51- 61- 71- 80-
Age-distribution of women with and without infected urine expressed
as a percentage of the total women in each group.
the urinary tract was the probable diagnosis in the great majority
of patients with sterile urine.
Recurrent Infections.-Of46 patients without initial infec-
This is slightly less than the incidence of persistent
in the other group.
was asymptomatic and
treatment in six, persisting in the remaining three.
Renal Function.-The blood
patients with initial infection.
showed definite changes of pyelonephritis on the intravenous
Minor caliceal changes without narrowing of the
renal cortex were seen in two other uninfected patients. Duplex
ureters occurred in three patientsfrom each group, and a horse-
shoe kidney in one patient without infection.
Nevertheless, on the history, an infection of
13 (28%) developed bacteriuria within three months (see
In 9 of the 13
urea was raised in one
five of these patients had
a minute, compared with three
One patient without infection
We are aware of only two other studies of infection of the
urinarytract ingeneral practice (Fryet al., 1962 ; Loudon and
Greenhalgh, 1962). Thismaybe due to difficulties in obtaining
adequate specimensof urine for culture from all patients in
difficulties inobtaining adequate co-operation from some of the
patients who originally went to their own doctor for personal
Of the 135 patients who consulted their doctors
we obtained asatisfactory specimenof urine for examination
in the laboratory in 130 (96%) and a complete follow-up in
Thestudywas designed to follow present methods of prac-
tice in New Zealand and to observe with bacteriological studies
the effectiveness or deficiencies of the regime used. We did not
expect to find the largenumber of patients presenting to their
doctors withsymptoms strongly suggestive of an acute infec-
tion in theurinarytract who did not have evidence of infec-
tion when the urine was cultured.
study using only mid-stream collections of urine when there
was no opportunityof repeating the examination before treat-
ment in most patients, we would have missed some of the
sterile urines and had many more doubtful infections of the
Apart from special surveys, mid-stream collec-
tion of urine is, we strongly believe, the correct method to use
inpractice when treating patients with urinary infections.
It is widely held that urinary infections in women
eitherduring pregnancy with dilatation of the upper urinary
tract orimmediately after pregnancy because of trauma to the
genital tract during labour.
married women without children
Loudon and Greenhalgh (1962).
incidence of these infections in married women before their
The increased incidence
Theorganisms responsible for infections of the urinary tract
in general conform to the pattern observed by Loudon and
The one difference was the number of
infections apparently due to coagulase-negative staphylococci
(12out of 88 infected urines).
regarded as occurring in mixed culture, often with urological
abnormalities, or after surgery to the genito-urinary tract.
was surprising to find a large number of uncomplicated infec-
tions causedbythis organism in these patients.
the nomenclature of this group is not uniform, and organisms
Gram-positivecoccibyothers may include coagulase-negative
In the course of this survey we found many
Had we attempted this
Infections of the urinary tract in
We also observed
is probably the result of sexual activity with
These organisms are commonly
as micrococci (Loudon and Greenhalgh,
Kunin et al. (1964) observed staphylococci.in
up to 16% of girls with recurrent infections of the urine.
Kleeman etal., 1960).
mens of urine were used in our study to avoid contamination.
The urine was cooled in a container packed with ice to reduce
organisms in such large numbers associated with pyuria and
proteinuria in our study suggests infection rather than con-
tamination of the urine.
patientsseen in hospital with obstruction in the lower urinary
tract or after instruments have been passed per urethram. Mixed
infections, however,were not exceptionalin our study, occurring
Loudon and Greenhalgh (1962)
similarly found mixed infections in 14 out of 143 patients in
Sulphafurazole was effective,
daysafter stopping treatment, in four out of every five patients
In vitro sensitivity predicted the failure in only seven
of the remaining 16 patients.
Of 115 patients seen in this study with
bacteriuriaduringthe next three months. The period of follow-
asymptomatic bacteriuria after this time.
asymptomatic bacteriuria is not known.
cleared of bacteria. Kass (1960) suggested that asymptomatic
bacteriuriaplaysakey partin the pathogenesis of pyelonephritis
and that thesepatients frequently develop overt symptoms.
The term "urethral syndrome," and synonyms, including
cystalgia, urethrotrigonitis, and non-specific urethritis, indicate
our poor understanding of the condition.
logicalfactors includeallergy (Kindall and Nickels, 1949), non-
specific infection (Folsom, 1931; Eberhart, 1958), congestion
of the urethra (Ormond, 1935), senile atrophy of periurethral
glands (Youngblood et al., 1957), obstruction (Davis,
andanxietyneurosis (Grayand Pingelton, 1956; Zufall, 1963).
Winsbury-White (1960) concluded that chronically
Bennett-Jones (1962) thought this was unlikely in the absence
oforganisms in the urine.
In comparing patients with and without infections in the
urine we observed several factors which led us to believe that
manycases of "urethral syndrome" are probably due to infec-
tion confined to the urethra and surrounding glands.
patients in both groups had received treatment for symptoms
of infection of the urinary tract in the past.
womenpredominatedand the age-distribution was similar, with
apeakincidence in the 21-25 age-group.
although more definite in patients with urine infection, were
similar in bothgroups.
period of observation in 13 out of 46 patients without initial
infection.Freedman(1960) reported cases with proved chronic
urethral syndromedid not include intractable cases with gross
granulomatous changes, polypi, and urethral strictures,
oftenreportedfrom urological clinics.
We do not have direct evidence to show that infection
Catheter specimens of urine precluded collecting the
specimen of urine which passed through the urethra.
swabs would have been of some, but limited, value.
of collection of these swabs
Disposablecatheters and catheter speci-
after collection, and quantitative
were made within one hour.
The growth of these
are commonly thought to occur only in
out of 77 patients.
as judged by the urine three
or recurring after
is short and other patients may well develop persistent
The importance of
Of 11 patients with
in five the urine spontaneously
In both groups
Bacteriuria developed during the short
Our group of patientswith the
Unless collected by
doctor with the patient on
would in many cases be only part of the normal flora from the
a suitable table, the bacteria found
vulva around the urethral orifice.
6 March 1965
Infection ofUrinaryTract-Gallagher et al.
6 March 1965
Infection of Urinary Tract-Gallagher et al.
An unselected group of 130 patients with symptoms of an
acute infection of the urinary tract have been studied from
Only 77 (59%) of these 130 patients had
Treatment with sulphafurazole was possible in
72, and was effective in 57 (79% of those treated). A high
incidence of infection observed in young women was apparently
related to sexual activity rather than child-bearing.
Of the patients with symptoms suggesting acute infections of
the urine 41 % had urine free of infection on culture.
patients were regarded as having the " urethral syndrome."
Adequate follow-up was possible in 115 (85 %) patients;
infection persisted or recurred in the three months after treat-
ment in 25 out of 69 patients with initial infection.
developed in the same period in 13 out of 46 patients without
Similarities between the patients with and
without definite infection in the initial urine suggest that the
" urethral syndrome "
urethra and adjoining glands.
spectrum of infections of the lower urinary tract.
This syndrome is part of the
We are grateful to Sister E. C. Budge, of the District Nursing
Service of the Auckland Hospital Board, for seeing patients in this
study, and to Mr. J. Holland, who, with technicians of the Central
Laboratory of the Auckland Hospital, examined the urines.
would thank Miss T. Hewitt for secretarial work involved in the
trial.Roche Products Ltd. generously gave a grant-in-aid and
supplied sulphafurazole (Gantrisin).
supported by a grant from the New Zealand Medical Research
Dr. J. Z. Montgomerie was
Bennett-Jones, M. J. (1962).
Brod, J. (1956).
Davis, D. M. (1956).
Eberhart, C. (1958).
Edwards, K. D. G., and Whyte, H. M. (1958).
Sci., 36, 383.
Effers0e, P., and Jensen, E. (1963).
Folsom, A. I. (1931).
Freedman, L. R. (1960).
E. L. Quinn and E. H. Kass, p. 345.
Fry, J., Dillane, J. B., Joiner, C. L., and Williams, J. D. (1962).
Gray, L. A., and Pingelton, W. B. (1956). 7. Amer. med. Ass., 162, 1361.
Guze, L. B., and Beeson, P. B. (1956).
Hodson, C. J. (1959).
Proc. roy. Soc. Med., 52, 669.
Jackson, G. G., Poirier, K. P., and Grieble, H. G. (1957).
Med., 47, 1165.
Kass, E. H. (1960).
In The Biology of Pyelonephritis, edited by E. L.
Quinn and E. H. Kass, p. 399.
Kindall, L., and Nickels, T. T. (1949).
Kleeman, C. R., Hewitt, W. L., and Guze, L. B. (1960).
(Baltimore), 39, 3.
Kunin, C. M., Deutscher, R., and Paquin, A. (1964).
Loudon, I. S. L., and Greenhalgh, G. P. (1962).
MacDonald, R. A., Levitin, H., Mallory, G. K., and Kass, E. H. (1957).
New Engl. 7. Med., 256, 915.
Ormond, J. K. (1935).
Relman, A. S. (1960).
In The Biology of Pyelonephritis, edited by E. L.
Quinn and E. H. Kass, p. 355. Churchill, London.
Weiss, S., and Parker, F., jun. (1939).
Wharton, L. R., Gray, L. A., and Guild, H. G. (1937).
Ass., 109, 1597.
Winberg, J., and Barr, M. (1960).
Winsbury-White, H. P. (1960).
Proc. roy. Soc. Med., 53, 1016.
Youngblood, V. H., Tomlin, E. M., and Davis, J. B. (1957).
(Baltimore), 78, 150.
Zufall, R. (1963).
Lancet, 1, 299.
Ibid., 1, 973.
7. Urol. (Baltimore), 76, 270.
Ibid., 79, 293.
Aust. 7. exp. Biol. med.
Lancet, 1, 1342.
7. Amer. med. Ass., 97, 1345.
In The Biology of Pyelonephritis edited by
New Engl. 7. Med., 255, 474.
7. Urol. (Baltimore), 61, 222.
Ibid., 43, 91.
Lancet, 2, 1246.
7. Urol. (Baltimore), 33, 483.
Medicine (Baltimore), 18, 221.
7. Amer. med.
Acta paediat. (Uppsala), 49, 203.
7. Amer. med. Ass., 184, 894.
Source of Elevated Serum Enzyme Activities in Patients with
Megaloblastic Erythropoiesis Secondary to Folic-acid Deficiency
B. A. ELLIOTT,* M.D., M.C.PATH.; A. F. FLEMING,t M.B., B.CHIR.
Brit. med. J., 1965, 1, 626-628
Elevated serum lactate dehydrogenase and a-hydroxybutyrate
dehydrogenase activities in patients with anaemia of pregnancy
have been reported by Fleming and Elliott (1964).
high activities were not related to the severity of the anaemia
but to the degree of megaloblastic marrow changes, and they
fell rapidly with
volume (P.C.V.) values rose, and before the restoration of
wholly normoblastic erythropoiesis.
events has been observed in the levels of serum lactate dehydro-
dehydrogenase (Elliott and Wilkinson, 1963) in patients on
treatment for pernicious anaemia.
These observations suggest the megaloblastic tissues as the
source of the elevated serum enzyme levels.
pernicious anaemia the megaloblasts have been reported to be
rich in enzymes (Heller et al., 1959), and it has been postulated
that these are released into the blood by the increased destruc-
tion within the marrow of the abnormal red-cell precursors
(Heller et ca., 1960a).
A similar process might explain the
dehydrogenase activities in patients with folic-acid deficiency.
folic-acid therapy before the packed
A similar sequence of
In patients with
Since these patients are commonly admitted to University
College Hospital, Ibadan, it was decided to investigate the
relation between their blood serum and bone-marrow lactate
dehydrogenase and a-hydroxybutyrate dehydrogenase activities.
*Senior Lecturer, Department of Chemical Pathology, University College
Hospital, Ibadan, Nigeria.
t Senior Registrar, Subdepartment of Haematology, University College
Hospital, Ibadan, Nigeria.
Materials and Methods
Patients Studied.-Six patients with Burkitt's tumour were
prior to chemotherapy.
change, and 10 were frankly megaloblastic.
patients were pregnant, and three had been recently delivered.
Serum Folic-acid Activities.-Activities were measured by
bioassay using Lactobacillus casei as the test organism (Herbert,
Serum Vitamin-B.2 Activities.-These were assayed using
L. leichmannii as the test organism (Rosenthal and Sarett,
Marrow Preparations.-Marrow specimens were collected
from the iliac crest using ethylenediamine-tetra-acetic acid as
Heparin and oxalate were not used, as they
partially inhibit enzyme activity (Plummer and Wilkinson,
17 patients with
Fourteen of these