RESEARCH LETTERS
Our findings provide strong circumstantial evidence that
small enhancing foci on MRI represent cancer foci and that
MRI is highly sensitive for the detection of invasive or in-situ
cancer foci. However, small cancer foci may never become
clinically apparent in a woman’s lifetime,1,2 and therefore
resecting them may not be necessary. We fear that the high
sensitivity of MRI for breast cancer detection would result in
many women suffering unnecessary mastectomies. Our
results suggest that MRI could be used to investigate
prospectively the clinical significance of unresected cancer
foci in order to convincingly determine their natural history
in the context of breast conserving surgery. Such a study
would be deemed ethical because breast MRI is still
considered experimental for preoperative planning of
surgery.
1
2
3
4
5
Vaidya JS, Vyas J, Chinoy RF, Merchant NH, Sharma OP, Mittra I.
Multicentricity of breast cancer: whole organ analysis and clinical
implications. Br J Cancer 1996; 74: 820–24.
Baum M, Vaidya JS, Mittra I. Multicentricity and recurrence of breast
cancer. Lancet 1997; 349: 208.
Weidner N, Semple JP, Welch WR, Folkman J. Tumour angiogenesis
and metastasis-correlation in invasive breast carcinoma. N Engl J Med
1991; 324: 1–8.
Buadu LD, Murakami J, Murrayama S, et al. Breast lesions:
correlation of contrast medium enhancement patterns with
histopathologic findings and tumour angiogenesis. Radiology 1996;
200: 639–49.
Heywang-Kobrunner SH, Veiweg P, Heinig A, Kuchler C. Contrastenhanced MRI of the breast: accuracy, value, controversies, solutions.
Eur J Radiol 1997; 24: 94–108.
All the cases of galactorrhoea were in women under age
50. In two, the patient was also on anti-psychotic
medication: the first of these had been prescribed a wide
variety of psychotropic medication previously, but she clearly
recalled the onset of galactorrhoea after starting
moclobemide, and its prompt cessation after withdrawal of
the drug. The second had been on chlorpromazine, 200 mg
four times a day, for 3 years, but galactorrhoea started 1
month after moclobemide was added.
The rate ratios show that galactorrhoea is significantly
associated with the use of moclobemide (assuming that the
rate on the SSRI drugs is baseline), although the relative risk
is not so great as with risperidone. There have been four
reports of galactorrhoea on moclobemide to the Committee
on Safety of Medicines (L Davies, personal communication).
This adverse event is biologically plausible, and prescribing
doctors should be aware of the possibility of its occurrence.
It does not appear in the Summary of Product
Characteristics for moclobemide.
1
2
3
4
Summary of Product Characteristics for Manerix (Moclobemide),
Roche, June 1997.
Freeman H. Moclobemide. Lancet 1993; 342: 1528–31.
Freemantle SN, Pearce GL, Wilton LV, et al. The incidence of the
most commonly reported events with 40 newly marketed drugs—a
study by prescription-event monitoring. Pharmacoepidemiol Drug Safety
1997; 6 (suppl 1): 1–62.
Mackay FJ, Dunn NR, Wilton LV, et al. A comparison of
fluvoxamine, fluoxetine, sertraline andparoxetine examined by
observational studies. Pharmacoepidemiol Drug Safety 1997; 6: 235–47.
Departments of Surgery (M Douek), Histopathology, and Radiology,
University College London Medical School, London W1P 7LD, UK
Drug Safety Research Unit, Bursledon Hall, Southampton SO31 1AA, UK
(N R Dunn)
Galactorrhoea with moclobemide
Clinical experience of UK medical
students
N R Dunn, S N Freemantle, G L Pearce, R D Mann
Moclobemide is a reversible inhibitor of monoamine oxidase
type A (RIMA), indicated for the treatment of major
depression. It decreases cerebral metabolism of
noradrenaline, dopamine, and serotonin, leading to
increased concentrations at neuronal synapses.1
Moclobemide also has the potential to raise serum prolactin,
presumably via serotonergic mechanisms,2 although this has
not hitherto been noted to have any clinical effects. Known
adverse drug reactions include sleep disturbance, dizziness,
nausea, headache, and confusional states.1
We did a study of moclobemide by prescription-event
monitoring (PEM), a technique of post-marketing
surveillance for newly-marketed drugs.3 We report the
incidence of galactorrhoea while on moclobemide, compared
with other psychotropic medications, also studied by PEM.
This analysis was data-driven, in response to a signal
generated by PEM output. The table shows adjusted rate
ratios for moclobemide versus four selective serotonin
reuptake inhibitor (SSRI) anti-depressants, fluvoxamine,
paroxetine, fluoxetine, and sertraline, none of which are
known to cause galactorrhoea,4 and risperidone. Risperidone
is an anti-psychotic, for which galactorrhoea is a listed sideeffect:
Drug
Cohort
sizetotal
Cohort
sizefemale
7 684
4 SSRI drugs 50 150
Moclobemide 10 835
Risperidone
Number
of
verified
reports
on treatment
Crude rate
per 1000
patientmonths
on treatment
Rate
Adjusted rate
standard- ratio (95% CI)†
ised for
age/sex*
3 500
25
1·05
0·96
34 565
6 824
4
6
0·03
0·20
0·03
0·20
*All study drugs as reference population. †SSRIs as base.
802
32·0
(13·7–69·5)
1
6·7 (2·7–15·0)
I C McManus, P Richards, B C Winder
In 1993 we reported the clinical experience of UK medical
students,1 and found that students entering in 1986, who
qualified in 1991/92, had less experience than those
entering in 1981 and who qualified in 1986/87. We now
describe data on 1991 entrants who qualified in 1996/97.
Final-year medical students in UK medical schools who
had previously taken part in prospective surveys of medicalstudent selection2 were sent a questionnaire about 4 months
before their final examinations which asked about their
clinical experience of the 14 acute medical conditions, 18
surgical operations, and 15 practical procedures common to
all three questionnaires.* Summary scores were calculated
as described previously,1 along with the simple total of the
three scores (figure). Sample sizes for the 1981, 1986, and
1991 cohorts were 337, 381, and 1481, corresponding to
65%, 51%, and 59% of possible respondents. Evidence
presented elsewhere suggests that respondents are an
unbiased subset of all students.3
Analysis of variance showed significant downwards linear
*The surgical operations were: amputation; appendicectomy; arterial
surgery; caesarean section; cardio-pulmonary bypass; cataract extraction;
(open) cholecystectomy, gastrectomy or V&P; (open) herniorrhaphy;
internal fixation of fracture; large bowel resection; laryngectomy;
mastectomy; mastoidectomy; removal of cerebral tumour; skin grafting;
thyroidectomy; transurethral prostatectomy. The acute medical conditions
were: acute glaucoma; acute left ventricular failure; acute psychosis; acute
upper GI bleeding; diabetic keto-acidosis; hypoglycaemia; hypothermia;
lobar pneumonia; meningitis; myocardial infarction; pneumothorax; status
asthmaticus; status epilepticus; sub-arachnoid haemorrhage. The practical
procedures were: arterial puncture; bladder catheterisation (male); bone
marrow aspiration; colonoscopy; electrocardiography; endotracheal
intubation, external cardiac massage; gastroscopy; insertion of CVP line;
lumbar puncture; setting up an IV drip; sigmoidoscopy; suturing in
casualty; urine testing; ventricular defibrillation.
THE LANCET • Vol 351 • March 14, 1998
RESEARCH LETTERS
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Clinical experience scores for students entering medical
school in 1981, 1986, and 1991
Top, median, 25th and 75th percentiles of total experience scores with
the 10th and the 90th percentiles. Width proportional to the sample
sizes, notches 95% CI for the median. Bottom, mean scores (±2
standard errors) for surgical operations, practical procedures, and acute
medical conditions.
trends across cohorts for all four scores (p<0·001). Analysis
of the individual experiences showed significant (p<0·05)
downwards trends for 13 of 14 acute medical conditions, 12
of 18 surgical operations, and 14 of 15 practical procedures.
Experience of only one medical condition (acute glaucoma)
and one practical procedure (colonoscopy) had increased
(p<0·05) across the time interval. We recognise that clinical
practice has inevitably changed to some extent over a
decade, as we discussed previously,1 but that is unlikely to
be able to explain the trend across almost all the measures
we looked at, be they operations, medical conditions, or
practical procedures.
The relative size of the downwards trend is large, being
about 1·2 standard deviations across a decade. The box and
whisker plots in the figure show that the score of the 25th
percentile for the 1981 cohort is similar to the median for
the 1986 cohort and to the 75th percentile for the 1991
cohort. Calculation of the absolute change (using a
transformation of the scores plotted in the figure) suggests
that the experience of the 1991 cohort was about 23% less
than that of the 1981 cohort.
Clinical experience has always been the mainstay of UK
medical training and any deterioration must be of concern.
The reasons for the decline described here are not entirely
clear, but may be related to changes either in NHS
organisation or in medical-school curricula. Radical changes
in the medical curriculum currently in process4 could
further alter the clinical experience of students, as also
might recent proposals to increase the number of medical
students.5
We thank the Economic and Social Research Council, the Leverhulme
Trust, and the Department of Health for grants in support of this work.
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THE LANCET • Vol 351 • March 14, 1998
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Centre for Health Informatics and Multiprofessional Education,
University College London Medical School, Whittington Hospital,
Highgate Hill, London N19 5NF, UK (I C McManus) and Northwick Park
and St Mark’s Trust, Harrow
Eclampsia complicated by bilateral
retinal detachments and abnormal
eye movements
Devender Roberts, Elizabeth Haslett, Marie Hickey-Dwyer,
James McCormack
We report a case of eclampsia complicated by bilateral
retinal detachments and abnormal eye movements
following treatment with magnesium sulphate (MgSO 4).
A 24-year-old woman (gravida 4, para 1) with a history
of placental insufficiency and fetal growth retardation was
admitted to the labour suite at 35 weeks’ gestation, with
nausea, vomiting, epigastric pain, and severe frontal
headache. Blood pressure readings were 190/123 mm Hg
with mean arterial pressures ranging from 140–144 mm
Hg. Proteinuria was present at 6 g per 24 h and
examination revealed bilateral brisk reflexes without
clonus. The blood pressure was stabilised with two 5 mg
boluses of intravenous hydrallazine and she was transferred
to theatre for delivery by caesarean section. She had an
eclamptic fit, 2 h after surgery, at mean arterial pressure
levels of 130–133 mm Hg on 10 mg/L maintenance
hydrallazine infusion. Eclampsia was managed with a
loading dose of 2·5 g MgSO 4 followed by a second dose of
5 g MgSO4 in 10 mL normal saline given over 15 min.
Maintenance magnesium sulphate at 2·5 g/h was infused
over the next 48 h and magnesium concentrations
remained therapeutic at 3–4 mmol/L. The clotting profile
showed a prolonged activated partial thromboplastin time
at 40·2 s with increased D-dimer and a platelet count of
363109/L. This was corrected with four units of fresh
frozen plasma and eight units of platelets. Postictally the
patient immediately described blurring of vision and
diplopia. Ophthalmological examination revealed a left
divergent squint with diplopia in all directions of gaze.
Fundoscopy revealed a total left retinal detachment and a
partial right retinal detachment which originated from the
peri-papillary region. Upbeat nystagmus was demonstrated
in upgaze and endpoint nystagmus on both dextroversion
and laevoversion. She had no demonstrable convergence.
Her visual acuity improved spontaneously over the next
48 h. 4 h after stopping MgSO 4 good convergence returned
and the diplopia resolved. Maintenance hydrallazine had
been stopped 12 h after the fit. Nystagmus resolved 2 days
after stopping MgSO4. On the 4th postoperative day,
fundoscopy revealed an isolated serous detachment in the
right eye and a small residual detachment in the left, which
subsequently resolved. There was complete resolution of
visual symptoms and return of normal visual acuity.
Our patient presented with two rare complications of
eclampsia. Retinal detachments have been reported
previously but this is, to our knowledge, the first report of
abnormal eye movements with the use of MgSO 4 following
an eclamptic fit. Retinal detachment as an ocular
complication of eclampsia was first described by von
Graefe in 1855.1 Fry reported that 10% of eclamptics have
associated retinal detachments, which are often bilateral. 2
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