16. Ji JD, Cheon H, Jun JB, Choi SJ, Kim YR,
osteoarthritis in guinea pigs. Arthritis &
anterior cruciate ligament. J Orthop Res.
DH, Kim SY, Sohn J. Effects of peroxisome
28. Setton LA, Elliott DM, Mow VC. Altered
O’Connor B, Heck D, Albrecht M Anterior
mechanics of cartilage with osteoarthritis:
human osteoarthritis and an experimental
model of joint degeneration. Osteoarthritis
osteoarthritis, not merely of cartilage injury
and repair. J Rheumatol. 1991;18:436-446.
29. Woo S, Young E, Suh J, Engevretsen, L.
17. Fahmi H, Di Battista JA, Pelletier JP, Mineau
as inducers of osteoarthritis. In: Kuettner
F, Ranger P, Martel-Pelletier J. Peroxisome
activators inhibit interleukin1-beta induced
nitric oxide and matrix metalloproteinase
30. Walsh DA. Pathophysiological mechanisms
18. Francois M, Richette P, Tsagris L, et al.
31. Bonnet CS, Walsh DA. Osteoarthritis,
Peroxisome proliferator-activated receptor
osteophyte formation during experimental
osteoarthritis. Osteoarthritis Cartilage.
metalloproteinase-1 via a novel composite
32. Chimich D, et al. Water content alters
25. Hellio le Graverand MP, Eggerer J, Vignon
19. Jiang C, Ting AT, Seed B: PPAR-gamma
ligament. J Biomech. 1992; 25(8):831-837.
osteoarthiritis. J Orthop Res. 2002;20:535-
Tanzer M, Zukor DJ, Antoniou J, Feige U,
Poole AR. Role of interleukin-1 and tumor
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articular cartilage after transection of the
Clinical application and review of typical and atypical antipsychotics in the treatment of delusional parasitiosis Nathan Y. Hoy,1 Patricia T. Ting, MSc, MD,2 Stewart Adams, MD3 1Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada 2Deparment of Dermatology and Cutaneous Sciences, Department of Medicine, University of Alberta, Edmonton, Canada 3Department of Dermatology, University of Calgary, Calgary, Canada
Correspondence and reprint requests to: Nathan Hoy, #110 Beddington Co-op Mall, 8220 Centre St. N.E., Calgary, Alberta, Canada T3K 1J7, Ph: (780) 289-3383, Fax: (403) 275-1143, Email: [email protected]ABSTRACT
advent of atypical antipsychotics have made
of both typical and atypical antipsychotics
Background: Delusional parasitosis (DP)
the latter the treatment of choice. Given the
paucity of randomized control trials and
psychosis characterized by a false belief
relatively recent introduction of atypicals,
pharmacologics. As well, we aim to provide
little is known about their efficacy in the
Traditionally, treatment revolved around
treatment in a dermatological setting.
typical antipsychotics, especially pimozide.
Objective: The purpose of this study is to Methods: Medline and EMBASE were
Pimozide’s adverse effect profile and the
review the evidence for the efficacy and use
searched for available literature for both
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
types of antipsychotics used in the treatment presence of parasites under the skin leading
to secondary excoriations, lichenification,
adverse side effects such as orthostatic
completed to allow for discussion of clinical
A number of case reports, case series, and
Results: Risperidone and olanzapine are
currently the most commonly used atypical
that the parasites exist; this stereotypical
presentation is referred to as “the matchbox
as efficacious as pimozide (full or partial
sign.”8 Furthermore, patients may attempt
The first double-blind crossover study was
remission rates of 68% and 90% respectively
to rid these “parasites” with anti-scabetic
permethrin cream or even perform harmful
fewer side effects. Other atypicals such as
skin cleansing rituals with disinfectants
patients had a decrease in Brief Psychiatric
quetiapine, aripiprazole and paliperidone
as well as risperidone long acting injections
rates > 75% in a limited number of patients,
Treatment of DP requires the differentiation
between the primary and secondary forms.
Treatment of secondary DP relies on treating
the underlying cause or cessation of the
Conclusion: Limited clinical studies
offending drug.10 Treatment of primary DP
significant improvement in 10 DP patients
has mostly revolved around typical and the
risperidone and olanzapine as first line
newer atypical antipsychotics, which have
3 weeks followed by a relapse following 2
trials are needed. We also review methods
weeks of placebo treatment and subsequent
to typical antipsychotics. We conducted a
improvement when pimozide was restarted.
literature search using combinations of the
treatment with atypical antipsychotics.
search terms: delusion*, parasitosis, typical,
own rating scale using symptoms of DP.13
Keywords: Delusional parasitosis, atypical
atypical, antipsychotics and treatment, in
published prior to May 1, 2010. For studies
involving typical antipsychotics, only those
with n≥20 (including placebo group) were
INTRODUCTION
reviewed, since these represent the most
The rates of partial and full remission are
influential studies on which the basis of
typical antipsychotic treatment is formed.
Zomer et al. (1998) found a partial to full
Due to the relatively recent introduction
remission rate of 61% (11 out of 18 patients)
belief that one is infected with parasites.1
of atypical antipsychotics in the treatment
in patients treated with pimozide compared
Thieberge first described this disorder in
of DP, the n values for these studies were
to 20% (3 out of 15) in the non-treatment
1894, and the name delusional parasitosis
significantly smaller; thus sample size was
group.16 A survey conducted by Lyell (1983)
not used as a definitive exclusion criterion.
prevalence of DP is not well established,
with pimozide demonstrated full or partial
but is considered rare. Overall, the female-
atypical. The criteria we considered included
to-male ratio of affected individuals is
the size of the study, with preference being
67%).17 Partial and full remission of DP in
given to larger sample sizes; whether or
patients treated with pimozide have been
diagnosis being slightly higher for females
reported as high as 87% (n = 46)18 to 100%
than males (mean age, 50 years to 40 years).3
within the same study, to control for variable
The classification of DP is as either primary
The long-term efficacy of treatment with
or secondary. Primary DP is characterized
pimozide was demonstrated in a follow-up
by a somatic delusion lasting for at least
population with respect to disease severity,
study by Lindskov and Baadsgaard (1985).19
Fourteen patients were followed up between
criterion A for schizophrenia and there can
be no underlying cause of the delusion.4
Typical antipsychotics
substance, organic causes, or other medical
used in the treatment of DP is pimozide.11
A systematic review conducted by Lepping
events, and neurodegenerative disease. A
Gilles de la Tourette syndrome in the United
et al. (2007) found a total of 92 patients
States, but it has also been shown to have
causes of DP is discussed by Huber et al.
label disorders, such as DP.10-19 Pimozide’s
primary mechanism of action is via central
Given that DP is a somatic delusion, patients
often initially present to dermatologists
improvement or were lost to follow-up.10 Of
advantage of pimozide over other typical
instead of psychiatrists with symptoms of
the 53 patients treated with pimozide, 50
antipsychotics is its weak noradrenergic
pruritis, crawling sensations attributed to the
had either full or partial remission (94%),
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
Table 1: Efficacy of typical antipsychotics in treatment of DOP
Two lost to follow-up for senility (n=1) and extensive relapse (n=1)
Table 2: Efficacy of atypical antipsychotics in treatment of DOP
7 (29) lost to follow up; 4 were switched to other drugs for varying reasons including requiring a different antipsychotic for co-morbid psychiatric disease, and intolerance of risperidone; 1 took it once and refused to continue medication
while 3 patients were non-compliant with
other hypotheses question this.21, 22 Atypical
treatment course – reasons for switching
treatment.10 Of note, the sample sizes for the antipsychotics used in the treatment of
other typical antipsychotic treatments were
DP that will be discussed are risperidone,
olanzapine, quetiapine, aripiprazole, and
intolerance of risperidone (Table 2).24-28
atypical antipsychotics
The most recent and largest retrospective
Atypical antipsychotics differ from typical
risperidone as the main treatment modality
case study followed 20 patients utilizing
antipsychotics in their various mechanisms
for DP. Gallucci and Beard23 first established
atypical antipsychotics for DP.26 Fifteen
of action and are generally associated with
risperidone as a potential treatment of DP.
patients were treated with risperidone as
less extrapyramidal symptoms. Meltzer et
Overall, of the 41 cases of DP treated with
the main atypical antipsychotic and 10 of
al. (1989)20 proposed that a preference for
risperidone that we reviewed, 28 had a full
them had full or partial remission, while 5
or partial remission, one had no change in
were lost to follow-up. Five patients were
symptoms and 12 were lost to follow up or
treated with olanzapine as the main atypical
this class of drugs, although a number of
were switched to another drug during the
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
antipsychotic. Of these patients, 4 had full or
and Lepping (2008) found a full or partial
partial remission, and 1 was lost to follow up.
schizophrenia, and Gilles de la Tourette
cases.34 The side effect profile of quetiapine
is generally limited to drowsiness, dizziness
treated with risperidone and one treated with quetiapine.27 Three of the 4
risperidone-treated patients experienced
prolongation, including Torsades de Pointes,
risk of extrapyramidal symptoms or adverse
total resolution of delusions; one of these
cardiac effects.36 Quetiapine’s excellent
three patients was also on lithium, another
blocking effects of the drug.7, 14, 35 These side
side effect profile combined with its high
was on sertraline and alprazolam as well,
effects, especially its cardiac effects and
remission rate makes it a potential treatment
The results of aripiprazole treatment in DP
patient had a decrease in delusions and was
have only been published for 4 patients to
on no other medications. The patient treated
date with all 4 demonstrating full or partial
with quetiapine showed partial remission
antipsychotics, because of their relatively
and was also on venlafaxine, clonazepam,
randomized control trials or placebo cross
antipsychotics. The largest review to date
over studies performed with aripiprazole
promising. Adverse effects of aripiprazole
risperidone long-acting injections (RLAI).29
Lepping,34 which concluded that atypical
include nausea and akathisia, but it is non-
The patient refused to take oral risperidone,
but accepted RLAI 25 mg IM every 2 weeks.
This dosage was titrated up to 37.5 mg IM
The atypical antipsychotics with the largest
disturbances.37 This excellent side effect
sample sizes in our review were risperidone
profile may make it beneficial to DP patients
improved, although complete remission was
antipsychotic used in the treatment of DP.
There are also newer atypical antipsychotics
The particular effectiveness of this drug has
antipsychotic used in the treatment of DP.
been linked to its high affinity for 5-HT
Paliperidone is the main active metabolite
receptors, a receptor which has been linked
of risperidone and it blocks 5-HT and D -
receptors. It has a long half-life of 24 hours,
aripiprazole.30-32 Rocha and Hara (2007)
which decreases the number of daily doses.
documented the first case of aripiprazole
side effect profile is superior to that of
As well, it decreases the risk of any potential
typical antipsychotics, there are instances
adverse drug reactions, which is especially
been produced by its use and it has been
associated with a mild increase in metabolic
simultaneously.33 The clinical efficacy of
had complete remission.31 Paliperidone, an
syndrome.32 An added benefit of risperidone
paliperidone as a treatment for DP needs
atypical antipsychotic approved by the FDA
is that it is the only atypical antipsychotic
to be confirmed by further case studies or
in 2006, has only been used in one DP case,
available as a long-acting depot. Long acting randomized control trials.
where an 88 year old man treated with the
injections are particularly useful in patients
CLINICAL IMPLICATIONS
who are demonstrating harmful behaviours and refusing to comply with oral treatment.
Diagnosis of DP is definitely within the
DISCUSSION
scope of a dermatology practice. However,
to help the patient accept their problem
makes initiating therapy in a dermatologist
treatment option for DP. The rates of full
office challenging. Patients often feel as
or partial remission were similar to the
if their symptoms are not being seriously
numbers reported in a systematic review by
Lepping et al. (2007).10 There have been a
treatment.34 Its side effect profile is also
to explain that the disease is psychotic in
number of smaller case reports and studies
superior to that of pimozide and it rarely
nature. Referral to a psychiatrist is often
utilizing other typical antipsychotics such as
causes extrapyramidal syndrome. However,
met with anger and frustration, resulting
haloperidol, trifluoperazine, flupenthixol and this medication is closely associated with
in the patient either seeking the opinion
metabolic syndrome and sedation.32 Its use
of another dermatologist or resorting to
excellent rates of full or partial remission.10
is still limited by a smaller body of evidence,
self-treatment, which may be potentially
Despite the past successes of pimozide, it is
but the fact that three patients treated with
no longer considered first-line treatment of
patient’s thoughts on you consulting an
DP, due to the advent of the safer atypical
due to intolerance suggests it may be a more
conditions more frequently. This will open the door to discussing the management
Furthermore, the long-term use of pimozide
Quetiapine had an excellent remission rate,
plan with a psychiatrist, while empowering
but with a small sample size (n=2), more
the patient to be actively involved in the
studies must be done in order to assess its
such as tardive dyskinesia, parkinsonism
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
4. DSM-IV-TR. Diagnostic and statistical
20. Meltzer HY. What’s atypical about atypical
antipsychotic drugs? Curr Opin Pharmacol.
rather than risk losing rapport with the
patient. Koo and Lee (2001) suggest making
American Psychiatric Association, 2000.
5. Huber M, Kirchler E, Karner M,Pycha R.
D(2) receptors and their role in atypical
the patient be more flexible in his or her
antipsychotic action: still necessary and
thinking if the biopsy returns negative; this
transporter. A new insight of etiology? Med
may even be sufficient. Biol Psychiatry.
may make it easier to convince the patient
6. Donabedian H. Delusions of Parasitosis.
22. Westerink BH. Can antipsychotic drugs be
classified by their effects on a particular
is initiated, it is advisable to offer the
medication as an empirical therapy while
23. Gallucci G, Beard G. Risperidone and
the treatment of delusions of parasitosis
sensations.8 Potential side effects of the
8. Koo J, Lee CS. Delusions of parasitosis.
the patient beforehand, to enhance patient
A dermatologist’s guide to diagnosis and
compliance. Considering the patient’s co-
treatment. Am J Clin Dermatol. 2001;2:285-
morbidities when selecting the particular
treatment of delusions of infestation. Int J
antipsychotic to be used can help tailor
the choice; for example, in a patient with
25. Healy R, Taylor R, Dhoat S, Leschynska
due to its potential for metabolic syndrome
side effects. Depot injections (risperidone)
10. Lepping P, Russell I, Freudenmann RW.
dermatology/ liaison psychiatry clinic. Br J
if the patient is willing to be regularly
delusional parasitosis: systematic review. Br
monitored by a psychiatric team. Working
in conjunction with the patient’s family
Parasitosis: a retrospective case series of 20
physician to monitor both the side effects of
patients. Int J Dermatol. 2010; 45:95-100.
the antipsychotic medication and course of
review. Am J Clin Dermatol. 2004;5:339-49.
the DP will reduce the risks of complications
from the therapy, especially if the patient
the treatment of delusional parasitosis.
refuses the involvement of psychiatry.
28. Nicolato R, Correa H, Romano-Silva MA,
CONCLUSION
Teixeira AL, Jr. Delusional parasitosis or
13. Ungvari G, Vladar K. Pimozide treatment
control trial directly comparing atypical
for delusion of infestation. Act Nerv Super
antipsychotics to typical antipsychotics,
clear treatment of choice for DP.10 However,
pimozide in clinical psychiatry: a review. J
Parasitosis. German Journal of Psychiatry.
classes as shown in Tables 1 and 2, it would
appear that atypical antipsychotics have a
infestation treated by pimozide: a double-
delusional parasitosis: Case report. Prog
lower side effect profile while achieving a
blind crossover clinical study. Acta Derm
partial to full remission rate similar to typical
antipsychotics. The reduction in adverse
16. Zomer SF, De Wit RF, Van Bronswijk JE,
31. Bennassar A, Guilabert A, Alsina M, Pintor
L,Mascaro JM, Jr. Treatment of delusional
compliance to treatment and help construct
parasitosis. A psychiatric disorder to be
treated by dermatologists? An analysis of
33 patients. Br J Dermatol. 1998;138:1030-
32. Sandoz A, LoPiccolo M, Kusnir D, Tausk
References:
17. Lyell A. The Michelson Lecture. Delusions
of parasitosis. Br J Dermatol. 1983;108:485-
parasitosis. Mayo Clin Proc. 2004;79:1470.
2. Wilson J, Miller H. Delusions of Parasitosis.
Archives of Dermatology and Syphilology.
Delusional parasitosis: a clinical profile. Int
paliperidone. Clin Exp Dermatol. 2009;34:375-7.
19. Lindskov R, Baadsgaard O. Delusions of
infestation treated with pimozide: a follow-
up study. Acta Derm Venereol. 1985;65:267-
generation antipsychotics in primary and
experience with 23 consecutive cases at an
secondary delusional parasitosis: outcome
academic medical center. Int J Infect Dis.
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
35. Wykoff RF. Delusions of parasitosis: a
review. Rev Infect Dis. 1987;9:433-7.
delusional parasitosis: experience in an
Aripiprazole in the treatment of primary
36. Milia A, Mascia MG, Pilia G, Paribello
delusional parasitosis. Br J Psychiatry.
Stem cells in cardiac repair: A review of the changing landscape of cardiovascular medicine Nicholas A. Avdimiretz, BSc Medical Student (2013), Faculty of Medicine and Dentistry University of Alberta, Edmonton, Canada
Correspondence to Nicholas Avdimiretz: Email: [email protected]Abstract Preamble Introduction to Cardiac Repair
Cardiac disease is the leading cause of death
developed countries. In fact, cardiovascular
its first applications for reconstituting
disease – including coronary heart disease,
increased by 90% in middle income groups,
hypertension, stroke, and congestive heart
failure – has ranked as the number one
pancreatic islet transplantation.5 More recent
cause of death in the US every year since
treatments include those for liver cirrhosis,
keep up with these statistics? Imagine if
Huntington’s disease, and Parkinson’s
epidemic.1 In 2007, heart disease accounted
disease.6 As for heart disease, the majority
heart post-myocardial infarction, or even
for 26% of all deaths in the US, resulting
in an age-adjusted death rate of 211 per
treatment of heart damage post-myocardial
is the future of cardiovascular medicine.
100,000 people.2 Also shocking is the cost
infarction (MI). How can myocardial repair
Regenerating myocardium is hardly an easy
of medication, health care services, and lost
undertaking; the heart contains about 20
productivity due to heart disease in the US:
incapable of naturally self-repairing itself?
million cardiomyocytes per gram of tissue,
a projected $508 billion in 2010.3 This cost
The heart does not experience regeneration
meaning – in the left ventricle alone – there
is not expected to decrease any time soon.
as the liver does; following MI, scar tissue
are approximately 4 billion cardiomyocytes
In Canada, the incidence of risk factors for
forms over the infarcted area. Therefore,
at risk during a heart attack. Many cells are
cardiac disease has increased substantially
required to replace damaged tissue, making
complete regeneration challenging. In light
of the rich therapeutic potential seen in
both adult and embryonic stem cells, it is no
the population),4 resulting in substantially
muscle following an MI is hardly an easy
surprise that biomedical research on these
more cardiovascular disease. What if there
cells has seen an intense amount of activity
existed a therapeutic technique to treat that
about 20 million cardiomyocytes per gram of
which physicians have for so long deemed
tissue, so there are approximately 4 billion
cardiomyocytes and skeletal myoblasts, to
incurable? What if one could regenerate the
cardiomyocytes at risk in the left ventricle
bone marrow stromal cells and peripheral
wounded heart after a myocardial infarction
blood CD34+ cells, a myriad of cell lines
that any repair therapy restores at least
have been tested to date. The last decade
bioengineer a new heart. This could be the
has seen an explosion of novel approaches
true regeneration would require 500 to 800
using these cells to restore cardiac function
million cells.7 In light of the therapeutic
post-infarction: from developing cell-based
Over the last decade, the utilization of
potential seen in both adult and embryonic
pacemakers and cardiac grafts, to building
stem cells to repair the damaged heart has
stem cells (coined ES cells by Martin in
bioartifical hearts. This review will paint a
seen an explosion of advancements. Novel
1981),8 it is no surprise that biomedical
picture of the rapidly changing landscape
therapeutic techniques will be addressed in
research on these cells has seen an intense
of cardiovascular medicine by elaborating
detail: the methods used and the resulting
amount of activity in the past decade.
applications of these innovations will be
of these approaches will be discussed, as
described. Limitations of these techniques
Stem Cell Sources
well as future developments. In the field of
cell-based cardiac repair, the possibilities
capacity to self-renew, but they are also
pluripotent; this means that stem cells can be induced to differentiate into cells
University of Alberta Health Sciences Journal • April 2012 • Volume 7 • Issue 1
Risks of Planned Vaginal Birth vs. Planned Cesarean Section after Previous Cesarean Section Risks of planned vaginal birth vs. planned cesarean section after previous cesarean Clinical question What are the risks of planned vaginal birth vs. planned cesarean section after previous cesarean section? Healthy women with previous cesarean section Planned vaginal birth after a) spo
Privatização dos serviços de água associada à intervenção da "troika" – consequências e dialéctica Intervenção em representação da Associação Água Pública na Audição Parlamentar realizada pelo Grupo Parlamentar do PCP sobre "as consequências do programa de privatizações no Vou referir só muito em geral a privatização da água que está em curso,