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Naimark Report commissioned by the
hospital and its documentary base. We
also had access to key Apotex and hos-
pital documents not available to the
Naimark Review. We therefore believe
we had a comprehensive set, from both
sides, of relevant information regarding
all players in the dispute. The central
conclusions of our report were inde-
pendently corroborated by the Dec. 19,
2001, report issued by the College of
Physicians and Surgeons of Ontario,5
who had the participation of some of
those very individuals who declined to
participate in our inquiry.
We would encourage your readers
to read our report, along with the sup-
plement discussing events since Octo-
ber 2001; both can be accessed at
www.dal.ca/committeeofinquiry. Con-
trary to the suggestion in your editorial,
the rights of “the study subject who
volunteers in research” are judged to
be a centrally important issue in our
report; indeed, they drive the wide-
ranging recommendations that we hope
will be taken up by all of those respon-
sible for the well-being of research par-
ticipants in Canada.
Patricia Baird
Professor, Department of Medical
Genetics
University Distinguished Professor
University of British Columbia
Vancouver, BC
Jon Thompson
Professor and Chair
Department of Mathematics and
Statistics
University of New Brunswick
Fredericton, NB
Jocelyn Downie
Associate Professor
Faculties of Law and Medicine
Dalhousie University
Halifax, NS
References
1. Gibson E, Baylis F, Lewis S. Dances with the
pharmaceutical industry [editorial]. CMAJ
2002;166(4):448-50.
2. Naylor CD. The deferiprone controversy: time
to move on [editorial]. CMAJ 2002;166(4):452-3.
3. Shuchman M. The Olivieri dispute: No end in
sight? CMAJ 2002;166(4):487.
4. Questions of interest [editorial]. CMAJ 2002;
166(4):413.
5. College of Physicians and Surgeons of Ontario.
Complaints Committee Decision and Reasons, Dec.
19, 2001:17. Available: www.caut.ca/english
/bulletin/2002_jan/default.asp (accessed 2002
June 7).
Alzheimer’s disease
and herpes
Herpes simplex virus type 1 (HSV1)
is present in latent form in the
brains of a high proportion of
elderly people1and is a risk factor for
Alzheimer’s disease in carriers of the
type-4 allele of the apolipoprotein E
gene (apoE-e4). ApoE-e4 is also a risk
factor for cold sores.2,3 We have sug-
gested that when HSV1 is reactivated
in the nervous system the resulting
damage is greater in apoE-e4 carriers
than in people who carry the other
apoE alleles. We recently detected anti-
bodies to HSV1 in cerebrospinal fluid,
substantiating our detection of HSV1
by polymerase chain reaction and
showing that it does indeed reactivate
(unpublished data). A clinical trial test-
ing a synthetic amyloid peptide as im-
munotherapy for Alzheimer’s disease
was recently halted because 4 patients
developed inflammation of the brain; in
“some” of these 4 patients, a virus was
detected in the cerebrospinal fluid.4
The results of René Verreault and
colleagues5 raise the intriguing possibil-
ity that viruses other than HSV1 may
directly influence Alzheimer’s disease.
Nonetheless, their findings could
equally well be explained by an indirect
effect: HSV1 reactivation can be trig-
gered by inflammation, and vaccines
would presumably prevent inflamma-
tion by preventing infection with the
target virus, thus indirectly preventing
HSV1 reactivation. Their study also
supports the possibility that vaccination
against HSV1 itself might prevent
Alzheimer’s disease; such vaccination is
feasible now that the age at which pri-
mary infection occurs is rising. In fact,
we have shown that vaccination of
HSV1-infected mice with mixed HSV1
glycoproteins prevents establishment of
latency in the brain.6
Finally, it would be interesting to
know if the trend detected by Verreault
and colleagues is dependent on the
apoE-genotype. Such dependence has
also been found for patients with herpes
simplex encephalitis7and for subjects
infected with HIV but who have not
yet developed AIDS.8
Ruth F. Itzhaki
Curtis B. Dobson
Molecular Neurobiology Laboratory
Department of Optometry and
Neuroscience
University of Manchester Institute of
Science and Technology
Manchester, UK
References
1. Jamieson GA, Maitland NJ, Wilcock GK,
Craske J, Itzhaki RF. Latent herpes simplex virus
type 1 in normal and Alzheimer’s disease brains.
J Med Virol 1991;33:224-7.
2. Itzhaki RF, Lin WR, Shang D, Wilcock GK,
Faragher B, Jamieson GA. Herpes simplex virus
type 1 in brain and risk of Alzheimer’s disease.
Lancet 1997;349:241-4.
3. Lin WR, Graham J, MacGowan SM, Wilcock
GK, Itzhaki RF. Alzheimer’s disease, herpes
virus in brain, apolipoprotein E4 and herpes
labialis. Alzheimers Rep 1998;1:173-8.
4. Elan and AHP provide an update on the phase
2A clinical trial of AN-1792. Dublin: Elan
Corporation; 2002. Available: www.elan.com
/NewsRoom/NewsYear2002/01182002.asp?Co
mponentID=2330&Sour%20cePageID=2333#1
(accessed 2002 Mar 8).
5. Verreault R, Laurin D, Lindsay J, De Serres G.
Past exposure to vaccines and subsequent risk of
Alzheimer’s disease. CMAJ 2001;165(11):1495-8.
6. Lin WR, Jennings R, Smith TL, Wozniak MA,
Itzhaki RF. Vaccination prevents latent HSV1
infection of mouse brain. Neurobiol Aging 2001;
22:699-703.
7. Lin WR, Wozniak MA, Esiri MM, Klenerman
P, Itzhaki RF. Herpes simplex encephalitis: in-
volvement of apolipoprotein E genotype. J Neu-
rol Neurosurg Psychiatry 2001;70:117-9.
8. Corder EH, Robertson K, Lannfelt L, Bog-
danovic N, Eggertsen G, Wilkins J, et al. HIV-
infected subjects with the E4 allele for APOE
have excess dementia and peripheral neuropathy.
Nat Med 1998;4:1182-4.
Spinal manipulation
versus mobilization
The commentary by Edzard Ernst1
alerts health professionals to the
possible complications of cervical ma-
nipulation. However, we feel that the
commentary would have been even
more clinically relevant if it had em-
phasized to physicians the distinction
between spinal manipulation tech-
niques and mobilization techniques.
Manipulation is defined as a small-
amplitude, high-velocity thrust tech-
Letters
CMAJ • JULY 9, 2002; 167 (1) 13
nique — a rapid movement over which
the patient has no control. Mobiliza-
tions are low-velocity techniques that
can be performed in various parts of
the available range based on the de-
sired effect. Mobilization techniques
have been shown to produce concur-
rent effects on pain, sympathetic ner-
vous system activity, and motor activ-
ity.2-4 Mobilizations can be prevented
by the patient5and are generally con-
sidered far safer than manipulations.
The majority of physiotherapists in
Canada use mobilization techniques on
the spine, as opposed to manipulation,
while many have trained in both and
are able to select the most appropriate
technique for the patient’s problem. It
would be a shame if physicians es-
chewed this technique by misrepre-
senting Ernst’s excellent commentary.
Meena Sran
Osteoporosis Program
Children’s and Women’s Health Centre
of British Columbia
University of British Columbia
Vancouver, BC
Karim Khan
Department of Family Practice
University of British Columbia
Vancouver, BC
References
1. Ernst E. Spinal manipulation: Its safety is uncer-
tain [editorial]. CMAJ 2002;166(1):40-1.
2. Sterling M, Jull G, Wright A. Cervical mobilisa-
tion: concurrent effects on pain, sympathetic
nervous system activity and motor activity. Man
Ther 2001;6(2):72-81.
3. Vicenzino B, Collins D, Benson H, Wright A.
An investigation of the interrelationship between
manipulative therapy-induced hypoalgesia and
sympathoexcitation. J Man Physiol Ther 1998;
21(7):448-53.
4. McGuiness J, Vicenzino B, Wright A. Influence
of a cervical mobilisation technique on respira-
tory and cardiovascular function. Man Ther
1997;2(4):216-20.
5. Maitland GD, Banks K, English K, Hengeveld
E, editors. Maitland’s vertebral manipulation. 6th
ed. Boston: Butterworth–Heinemann; 2001.
[The author responds:]
The comments by Meena Sran and
Karim Khan offer an important
clarification. The risks of mobilization
seems indeed to be much smaller than
those of spinal manipulation, though
truly convincing data are not presently
available. I was interested to learn that
many Canadian physiotherapists have
training in both methods and “select
the most appropriate technique for the
patient’s problem.” This begs the ques-
tion of how the most appropriate tech-
nique is determined. A recent analysis1
of 64 previously unpublished cases of
complications after upper spinal manip-
ulations demonstrated that no factors
are identifiable from the clinical history
or physical examination of the patients
that would help isolate patients at risk.
Essentially, this means everyone is at
risk. Spinal manipulation is undoubt-
edly the mainstay of chiropractors, and
it is not surprising that the vast majority
of complications happen in the hands of
chiropractors.2In my personal experi-
ence, physiotherapists in Europe use
spinal manipulation less frequently and
with more discrimination than chiro-
practors in Canada.
Edzard Ernst
Department of Complementary Medicine
School of Sport and Health Sciences
University of Exeter
Exeter, UK
References
1. Haldeman S, Kohlbeck FJ, McGregor M. Un-
predictability of cerebrovascular ischemia associ-
ated with cervical spine manipulation therapy.
Spine 2002;27:49-55.
2. Di Fabio RP. Manipulation of the cervical spine
risks and benefits. Phys Ther 1999;79:50-65.
Clinical practice guidelines:
breast cancer pain
It is disturbing to read the 2001 up-
date of the clinical practice guideline
on the management of chronic pain in
patients with breast cancer as summa-
rized in CMAJ by Chris Emery and
colleagues.1In the full text of these
guidelines the authors state that bone
pain from vertebral metastases is very
common; however, there is absolutely
no mention of surgical stabilization
techniques despite the fact that they are
an effective evidence-based option for
treating mechanical axial skeletal pain
due to bone metastases.
Among their descriptions of treat-
ment options the authors are careful to
include descriptions of complementary
techniques with little or no evidence for
their effectiveness, including neurosur-
gical ablative procedures such as rhizo-
tomy and cordotomy, and psychother-
apy. They fail to mention the excellent
outcomes seen with surgical stabiliza-
tion of pathological vertebral fractures
and impending fractures. They even
state that “except for spinal cord com-
pression, neurosurgical interventions
are rarely required in the management
of cancer pain.” There is now a large
body of literature that supports the sur-
gical decompression and stabilization of
spinal metastases as effective palliation
of mechanical pain (not only for
metastatic epidural spinal cord com-
pression) with acceptable levels of mor-
bidity.2–5 In fact, surgery followed by
radiation appears to be more effective
than radiation alone in improving local
pain control and survival and reducing
postoperative morbidity.2–6
No longer is it acceptable practice
to deny surgical stabilization to appro-
priate patients with vertebral metas-
tases. At the Combined Neurosurgical
and Orthopaedic Spine Program at
Vancouver General Hospital we have
reported favourable outcomes in these
surgically treated patients; we con-
tinue to follow their outcomes
prospectively and are perfoming an
economic evaluation of surgical treat-
ment in these patients. It is a pity that
the guidelines published by Emery
and colleagues continue to perpetuate
the lack of appropriate referral and
access to effective spinal surgical care
for this often inadequately palliated
patient population.
Marcel Dvorak
Charles G. Fisher
Combined Neurosurgical and
Orthopaedic Spine Program
Vancouver General Hospital
Vancouver, BC
References
1. Emery C, Gallagher R, Hugi M, Levine M, for
the Steering Committee on Clinical Practice
Guidelines for the Care and Treatment of Breast
Cancer. Clinical practice guidelines for the care
Correspondance
14 JAMC • 9 JUILL. 2002; 167 (1)