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seen
on
further
ultrasonography
and
in
biopsy
speci-
mens.
Several
treatments
were
required
for
each
tumour,
and
injecting
alcohol
was
often
associated
with
considerable
pain,
whereas
our
patients
did
not
report
pain.
These
reports
did
not
mention
changes
seen
on
ultrasound
scans
during
or
immediately
after
injection,
which
we
found
useful
in
laser
treatment.
The
most
important
advantage
of
the
laser
is
its
precision.
It
is
unlikely
that
it
will
ever
be
possible
to
predict
the
extent
of
necrosis
around
a
site
at
which
absolute
alcohol
has
been
injected
with
an
accuracy
comparable
to
that
already
possible
with
the
laser
technique.
In
conclusion,
interstitial
laser
hyperthermia
is
feasible
and
seems
to
be
safe.
A
multiple
fibre
system
makes
it
feasible
to
treat
tumours
of
clinically
relevant
size
in
the
centre
of
solid
organs.
The
real
challenge
for
the
future
will
be
to
develop
diagnostic
techniques
that
disclose
exactly
how
far
individual
tumours
extend
in
a
wider
range
of
organs
(unlike
the
well
defined
tumours
treated
in
this
pilot
study)
and
to
establish
the
conditions
of
laser
treatment
that
give
complete
tumour
ablation
with
safe
healing.
This
combination
of
technologies
may
be
valuable
for
treating
otherwise
untreatable
tumours
in
a
range
of
solid
organs
and
for
the
primary
treatment
of
small
neoplasms
such
as
tumours
of
the
prostate
and
adrenal
glands.
We
thank
Mr
R
C
G
Russell,
Mr
P
Hawley,
Mr
W
Slack,
and
the
late
Professor
C
G
Clark
for
referring
these
patients
and
for
permission
to
report
these
results.
We
also
thank
Dr
T
N
Mills,
Mr
P
Hill,
and
Miss
L
A
Potter
of
the
department
of
medical
physics
for
their
help.
Mr
Steger
was
supported
by
Living
Technology
Ltd,
Glasgow,
and
Dr
Bown
by
the
special
medical
development
on
lasers
from
the
Department
of
Health
and
by
the
Imperial
Cancer
Research
Fund.
1
Storm
KF,
Kaiser
L-R,
Goodnight
JE,
ei
al.
*Fhermotherapy
for
melanoma
metastascs
in
liser.
Cancer
1982;49:
1243-s.
2
Lindholm
C-E,
K'ellan
E,
Nilson
P,
Hertzman
S.
Microwave
indtuccd
hy-perthermia
and
radiotherapy
in
human
superficial
tumotirs
clinical
results
with
a
comparative
study
of
combined
treatment
versus
radiothcrapy
alone.
lnr,7
s'p
1erpthermia
1987;3:393-41
1.
3
Milligan
AJ.
Whole
body
hypcrthertmia
iinductioni
tcchniqtucs.
Cancer
Res
1984;44
(10
Suppl):4869-72.
4
Shiplc
WU,
Nardi
GL,
Cohen
AM,
Cliftoin
Ling
C.
Iodine-'"'
implant
and
cxtcrnal
bceam
irradiation
in
patienits
with
localized
pancreatic
carciinoma.
Cancer
19X0;45:709-14.
5
Dritclilo
A,
(irant
EG,
Harter
KW;,
Holt
RWY,
Rustigi
SN,
Rodgers
JE.
Intcrstitial
radiation
therapy
for
hcpatic
metastases:
sonographic
guidance
for
applicator
placement.
Am,7
Radtol
1986;164:275-8.
6
Bown
SG.
Phototherapy
of
tumors
World.7
Surg
1983;7:700-9.
7
Matthewson
K,
Coleridge-Smith
1,
O'Sullisan
JP,
Northfield
PIC,
Bown
SG.
Biological
effects
of
intrahepatic
Nd-YAG
lascr
photocoagulation
in
rats.
Gastrosnicrologv
987;93:550-7
8
Stcger
AC,
Bown
SG,
Clarke
C(G
Intcrstitial
lascr
hypcrthermia-stttdics
in
the
nortmal
liver.
fBrj
Surg
1988;75:59X
9
Mlatthewson
K,
Coleridge-Smith
1P,
Northlfield
I,,
Bowil
SG.
Cotoparisonl
of
contintUoUs
uave
attd
puIlsed
excitationi
for
interstitial
Nd-YA(
iidttdccd
hvprthermia.
lasers
inn
Medical
Sciunce
1986;1
197-201.
10
Hashimoto
1).
Ultrasonography
guidcd
lasers
and
sphcric
lasers.
In:
Ricmann
JF,
Ell
C,
cds.
Lasers
in
gastrocnicrologs'
Gec)rg
Thiemc
V'crlag
Inc,
Stuittgart:
Thicmc
P'uLblishicrs,
1989:134-8.
11
Godlewski
(i,
Sambtc
P,
Eledjam
JJ,
Pignodel
C,
Ould-Said
A,
Bourgeois
JM.
A
new
device
ftr
inducing
deep
localised
vaptrisation
in
liver
with
the
Nd-
YAG
laser.
lasers
inM
edical
Science
19XX;3:
111-7.
12
Shiina
S,
Yasuda
H,
Aluto
H,
et
al.
P'ercutaneous
ethanol
iijectioin
in
the
treatment
of
liser
neoplasms.
Amj7
Radiol
1987;149:949-52.
13
Livraghi
T,
Fcsti
Ml,
Monti
F,
Salmi
A,
Vcttori
C.
US-guidcd
pcrCutatlcous
alcohol
iIjectioIn
of
small
hepatic
aind
abdomiial
tuimiors.
Radiology
1986;161
:3(9-12.
(A.4septsd31
.IlaY
1919
Departments
of
Rheumatology
and
Clinical
Pharmacology,
St
Bartholomew's
Hospital,
London
ECIA
7BE
Peter
Fisher,
FFHOM,
visitintg
rheumatologist
Alison
Greenwood,
SRN,
clinical
metrologist
E
C
Huskisson,
FRCP,
head
of
rheumatolopv
department
Paul
Turner,
FRCIP,
projfessor
of
clinical
pharmtacology
Laboratoires
Boiron,
69110
Ste
Foy
les
Lyon,
France
Philippe
Belon,
MD,
research
director
Correspondence
to:
Dr
Fisher.
BrAfedj
1989;299:365-6
Effect
of
homoeopathic
treatment
on
fibrositis
(primary
fibromyalgia)
Peter
Fisher,
Alison
Greenwood,
E
C
Huskisson,
Paul
Turner,
Philippe
Belon
In
scientific
research
negative
results
are
often
more
difficult
to
interpret
than
positive
ones,
as
was
shown
by
a
clinical
trial
in
which
the
homoeopathic
medicine
Rhus
toxicodendron
6x
was
compared
with
a
placebo
and
fenoprofen
in
the
treatment
of
osteoarthritis.
The
homoeopathic
medicine
was
found
to
be
ineffective
whereas
fenoprofen
gave
an
improvement.'
There
were
two
interpretations:
either
the
effects
of
homoeo-
pathy
are
only
a
placebo
effect-that
is,
a
true
negative
-or
the
result
was
a
false
negative
one
because
of
flaws
in
the
design.
Another
trial
had
previously
suggested
that
homoeopathy
was
effective
in
rheuma-
toid
arthritis.
We
designed
a
trial
to
clarify
these
results
by
overcoming
the
methodological
criticisms
while
retain-
ing
a
rigorous
design.
The
main
problem
in
designing
clinical
trials
of
homoeopathy
is
that
prescriptions
are
based
on
criteria
such
as
the
pattern
of
symptoms
as
well
as
the
diagnosis.
A
clinical
trial
based
solely
on
diagnosis
is
therefore
inappropriate.
In
a
pilot
study
we
had
shown
that
R
toxicodenidron
6c
was
the
most
commonly
indicated
homoeopathic
medicine
for
fibrositis
in
our
patients,
being
indicated
in
42%.
Patients,
methods,
and
results
We
used
the
diagnostic
criteria
of
Yunus
et
al
for
fibrositis.'
Only
patients
with
this
syndrome,
in
whom
the
homoeopathic
medicine
R
toxicodendron
6c
was
positively
indicated
were
entered
into
the study.
Thirty
patients
meeting
the
admission
criteria
were
recruited
in
the
rheumatology
clinic
of
this
hospital.
The
clinical
characteristics
of
the
patients
were
similar
to
those
of
other
reported
series
regarding
age,
sex
distribution,
duration
of
symptoms,
modalities,
and
number
of
tender
points.
The
trial
was
double
blind,
placebo
controlled,
and
of
crossover
design.
After
entry
there
was
no
further
contact
between
the
homoeopathic
doctor
and
the
patient
until
the
treat-
ment
was
finished.
The
clinical
metrologist
dispensed
the
treatment
and
performed
the
assessments
and
analyses
blind.
Patients
received
active
treatment
and
an
identical
placebo
for
one
month
each
in
random
sequence.
The
dose
was
two
tablets
sucked
three
times
daily.
The
active
preparation
was
R
toxicodendron
6c
(Boiron)
prepared
from
a
tincture
of
the
leaves
of
poison
oak
diluted
1:99
in
ethanol
and
then
vigorously
shaken.
This
process
was
repeated
six
times
to
give
the
6c
potency-a
dilution
of
102
of
the
tincture.
This
was
then
put
up
on
125
mg
lactose
tablets
(2%
volume
per
weight).
Preparation
was
as
specified
in
the
French
national
pharmacopoeia.
The
placebo
was
identical
lactose
tablets
to
which
only
pharmaceutical
ethanol
had
been
added
(2%
volume
per
weight).
Blind
testing
of
the
active
and
placebo
preparations
for
a
battery
of
drugs
yielded
negative
results.
Assessment
comprised
the
number
of
tender
spots,
10
cm
visual
analogue
scales
of
pain
and
sleep,
and
overall
assessment.
Comparison
was
made
between
values
at
the
end
of
active
and
placebo
treatment
periods.
The
patients
did
better
in
all
variables
when
they
took
active
treatment
rather
than
placebo.
The
number
of
tender
spots
was
reduced
by
about
a
quarter
(p<0005).
We
reduced
subjective
data
to
nominal
measurements
(worse
or
better).
If
the
null
hypothesis
were
correct
the
direction
of
change
after
placebo
and
active
treatment
would
be
randomly
distributed.
Analysis
showed
a
significant
difference
in
favour
of
the
homoeopathic
medicine
(table).
Overall
assess-
ment
also
showed
a
preference
for
the
active
treatment,
which
was
not
significant.
BMJ
VOLUME
299
5
AUGUST
1989
365
Assessment
of
patients
with
fibrositis
after
treatment
with
Rhus
toxicodendron
(ac-tive)
and
placebo
Placebo
Active
p
Value
Mean
No
of
tender
points
14-1
10-6
<0.005*
No
of
patients
with
improved
pain
or
sleep
(visual
analogue
scores)
27
53
0-0052t
*Wilcoxon
rank
sum
test.
tPaircd
t
test.
Comment
Fibrositis
(primary
fibromyalgia)
is
a
controversial
condition
but
is
becoming
increasingly
accepted.4
It
is
difficult
to
treat.
We
showed
that
the
homoeopathic
medicine
R
toxicodendron
6c
was
effective
for
a
selected
subgroup
of
patients
with
fibrositis.
The
improvement
in
tenderness,
which
is
the best
discriminator
of
fibrositis,5
was
particularly
distinct.
The
improvement
experienced
by
our
patients
while
receiving
active
treatment
was
at
least
as
great
as
that
reported
for
any
other
treatment
that
has
been
assessed
double
blind.
We
thank
Jean
Boiron
for
his
advice
and
encouragement.
I
Shipley
M,
Berry
H,
Brostcr
G,
Jeilkinis
M,
Closer
A,
Williams
1.
Conitrolled
trial
ott
homoeopathic
treatment
of
osteoarthritis.
Lancet
1983;i:97-8.
2
Gibsott
RU,
Gibson
SLMNI,
MacNeill
DA,
Watson-Buchanan
W.
Homoeopathic
therapy
in
rhettmatoid
arthritis:
evalitation
by
double-blind
clinical
trial.
Br]
Clin
Phtarmacol
1980;9:453-9.
3
Yttnus
M,
Alasi
AT,
Calabro
JJ,
et
al.
IPrimary
fibromyalgia
(fibrositis):
clinical
study
of
50
paticnts
with
matched
normal
controls.
Semin
Arthritis
Rthe2m
1981;11:151-71.
4
Yunus
MB.
Fibromyalgia
syndrome:
new
research
on
an
old
condition.
Br
Medj
1989;289:474-5.
S
Wolfe
F,
Hawley
DJ,
Cathey
MA,
et
a/.
Fibrositis:
symptom
frequency
and
criteria
for
diagnosis.]7
Rheumatol
1985;12:1159-68.
(Accepted
28
A-pril
1989)
Department
of
Medicine,
General
Hospital
Linz,
A
4020,
Austria
G
Biesenbach,
MD,
registrar
in
nephrology
J
Zazgornik,
MD,
professor
of
medicine
Correspondence
to:
Dr
Biesenbach.
BrMedj
1989;299:366-7
Incidence
of
transient
nephrotic
syndrome
during
pregnancy
in
diabetic
women
with
and
without
pre-existing
microalbuminuria
G
Biesenbach,
J
Zazgornik
Considerably
different
changes
in
renal
protein
excre-
tion
have
been
reported
in
diabetic
women
during
pregnancy.'
2
In
pregnant
diabetics
with
pre-existing
macroproteinuria
(¢0
5
g
protein
in
24
hour
urine
samples)
there
is
often
a
clear
increase
in
the
protein-
uria,
often
resulting
in
development
of
the
transient
nephrotic
syndrome.34
In
diabetic
women
with
albu-
min
excretion
<30
mg/day
(normoalbuminuria)
or
30-250
mg/day
(microalbuminuria)
before
pregnancy,
however,
the
syndrome
is
rarely
observed
during
pregnancy.
We
determined
to
what
extent
micro-
albuminuria
(incipient
diabetic
nephropathy)
affects
the
alterations
of
renal
protein
excretion
and
the
variables
of
kidney
function
during
and
after
preg-
nancy
and
the
incidence
of
the
syndrome
during
pregnancy
in
these
women.
Patients,
methods,
and
results
We
investigated
seven
pregnant
women
with
type
I
diabetes
and
pre-existing
normoalbuminuria
(mean
(SD)
age
22
(5)
years,
mean
(SD)
duration
of
diabetes
10
(4)
years)
and
seven
pregnant
type
I
diabetics
with
pre-existing
microalbuminuria
(mean
(SD)
age
23
(5)
years,
mean
(SD)
duration
of
diabetes
11
(3)
years).
All
women
delivered
between
36
and
40
weeks'
gestation.
Before
one
woman
became
pregnant,
during
weeks
12,
24,
28, 32,
and
36-40
of
pregnancy,
and
in
weeks
4,
12,
and
24
after
delivery
we
measured
serum
creatinine
concentration
(autoanalyser),
creatinine
clearance,
glycated
haemoglobin
concentration
(Biorad),
blood
pressure
(Riva
Rocci),
albumin
concentration
(immunodiffusion),
and
total
protein
concentration
(Biuret
method)
in
24
hour
urine
samples.
In
the
seven
diabetic
women
with
pre-existing
normoalbuminuria
there
was
a
5
9-fold
increase
in
albumin
and
a
5-7-fold
increase
in
total
protein
excretion
in
urine
during
pregnancy.
In
the
seven
diabetic
women
with
microalbuminuria
we
found
a
5
9-fold
increase
in
albumin
excretion
and
a
10
0-fold
increase
in
total
protein
excretion.
After
delivery
the
protein
excretion
fell
to
the
values
before
pregnancy
in
all
patients.
The
difference
between
the
absolute
increase
of
proteinuria
in
the
two
groups
was
signifi-
cant
(p<0005,
unpaired
t
test).
Blood
pressure
and
metabolic
control
did
not
differ
significantly
during
pregnancy
in
both
groups
(table),
and
the
variables
of
renal
function
did
not
differ
between
normo-
albuminuric
and
microalbuminuric
women.
The
transient
nephrotic
syndrome
with
protein
excretion
>3
g
in
24
hour
samples
of
urine
(3
178
g,
4907
g,
and
4-761
g)
occurred
in
three
of
the
seven
women
with
pre-existing
microalbuminuria
but
in
none
of
the
seven
with
pre-existing
normoalbuminuria.
Comment
The
transient
nephrotic
syndrome
is
rare
in
preg-
nant
diabetics
without
pre-existing
heavy
proteinuria
and
decreased
glomerular
filtration
rate
as
well
as
in
healthy
pregnant
women.'
The
extent
to
which
albumin
excretion
before
pregnancy
influences
the
increase
in
proteinuria
and
the
alterations
of
the
kidney
function
during
pregnancy
has
not,
to
our
knowledge,
been
previously
investigated
in
diabetic
women.
In
our
patients
with
normoalbuminuria
the
increase
in
proteinuria
during
pregnancy
remained
within
the
physiological
range
seen
in
healthy
pregnant
women.4'
In
the
diabetic
women
with
pre-existing
microalbuminuria
the
increase
in
proteinuria
during
pregnancy
was
significantly
higher.
Obviously
the
glomerular
basement
membrane
develops
a
greater
permeability
for
protein
during
pregnancy
in
diabetic
women
with
pre-existing
microalbuminuria
in
com-
Urtnary
protein
excretion
and
renal
function
before,
during,
and
after
pregnancy.
Values
are
means
(SD)
Diabetics
with
normoalbuminuria
Diabetics
with
microalbuminuria
Before
Third
trimester
24
Weeks
Before
Third
trimester
24
Weeks
pregnancy
of
pregnancy
after
deliverv
pregnancy
of
pregnancy
after
deliverv
Albumin
in
urine
(mg/day)
12
(3)
71('34)
13
(4)
80
(45)
478
(247)
114
(74)
Total
protein
in
urine
(g/day)
0-073
(0-056)
0
417
(0
142)
0
096
(0-073)
0
233
(0-186)
2
353
(1
211)
0-239
(0-107)
Serum
creatinine
(,tmol/l)
79(13)
68(10)
85
(7)
71(15)
63(9)
79(13)
Creatinineclearance(mlUs)
1
72
(0
18)
2-07
(0-118)
1
72
(0
17)
1
83
(0-22)
2-12
(0
40)
1
80(0
28)
Blood
pressure
(mm
Hg)
120
(9)/79
(5)
121
(7)l77
(5)
118
(7)/79
(6)
118
(8)/80
(7)
118
(6)/79
(6)
117
(6)/78
(5)
Glycatedhaemoglobin(%)
6-2(1-1)
4-7(0
8)
6-2(0
6)
6-8(0
6)
5-4(0
5)
6-8(0
5)
366
BMJ
VOLUME
299
5
AUGUST
1989
