journal

Transcription

journal

VOL. 17 - (1) - APRIL 2007
ISSN 1018-2357
The European Journal of
Companion
Animal Practice
Clinical efficacy of Pimobendan versus Benazepril for
the treatment of acquired atrioventricular valvular
disease in dogs
Rabbit dentistry
29
55
How to look at Radiographs
79
Dealing with MRSA in Companion Animal Practice
85
THE OFFICIAL JOURNAL OF FECAVA
Federation of European Companion Animal Veterinary Associations
www.fecava.org
Volume 17 (1) April 2007
The Official Journal of the Federation of
European Companion Animal Veterinary
Associations (FECAVA).
EDITOR
Dr. Keith Davies
43, Hill Top Road - Newmillerdam
GB-WF2 6PZ Wakefield
Tel.: (44) 1924 250486 (UK)
(33) 4 68 39 50 29 (F)
Fax: (44) 1924 259572
Email: [email protected]
PRODUCTION COMMITTEE
Dr Ellen BJERKÅS, FECAVA President
Dr. Keith DAVIES, Editor
Dr. Joaquin ARAGONES
Dr. Peter STERCHI
Dr. Tiina TOOMET
Dr. Johan VAN TILBURG
Dr. Simon KLEINJAN
EDITORIAL BOARD (FOR NEW WORK)
Dermatology
Didier-Noël CARLOTTI (F)
Cardiology
Anna TIDHOLM (S)
Internal medicine
Åke HEDHAMMAR (S)
Orthopaedics
Aldo VEZZONI (I)
Surgery
Simon ORR (GB)
Imaging
Ingrid GIELEN (B)
Eiliv SVALASTOGA (DK)
Reproduction
Stefano ROMAGNOLI (I)
Dentistry
Peter FAHRENKRUG (D)
Ophthalmology
Ellen BJERKÅS (N)
Neurology
Andre JAGGY (CH)
Endocrinology
Mike HERRTAGE (GB)
Oncology
Jane DOBSON (GB)
New Material should be sent to:
Prof. Ellen BJERKÅS,
Norwegian School of Veterinary Science,
PO Box 8146-Dep, N- 0033, Oslo.
ADVERTISEMENT BOOKINGS
Sould be sent to: The Editor (see above)
CIRCULATION
Members of the Associations belonging to the
Federation of European Companion Animal
Veterinary Associations receive the European
Journal of Companion Animal Practice at no
charge (25,000 copies).
PURCHASE OF COPIES
For others interested in purchasing copies the
price is 52 € per Volume (2 issues). Orders should
be sent to:
FECAVA HQ, rue Defacqz 1, B-1000 Brussels
EDITORS NOTE
The language of EJCAP is English (UK). Where
reprint papers have been translated, or where
other versions of English were originally used,
those have been translated to English (UK).
THANKS
The production Committee of EJCAP thanks:
Dr. Bob Gibbons
Dr. Edmund Shillabeer
Dr. Craig Harrison
who have spent time correcting the translations.
Roto Smeets GrafiServices,
p.o. box 7052, 3502 KB Utrecht,
The Netherlands. Tel +31 (30) 282 28 22
DISCLAIMER
“The Federation of European Companion
Animal Veterinary Associations and the
Production Committee of the European Journal
of Companion Animal Practice accept no
responsibility for any omissions and/or errors in
information printed in this journal.We specifically
draw readers attention to the need to follow
instructions of manufacturers products. In any
specific situation readers are strongly advised not
merely to rely on the material contained in the
journal. Any views and opinions expressed are
those of the writer and not the Federation or the
Production Committee.”
The European Journal of
Companion Animal Practice (EJCAP)
Contents
The Federation of European Companion Animal
Veterinary Associations (FECAVA)
Editorial
News
2
5
9
CARDIOLOGY AND RESPIRATORY SYSTEM
A retrospective study of clinical findings, treatment and outcome in
143 dogs with pericardial effusion
M. Stafford Johnson, M. Martin,S. Binns , M. J. Day
15
CT-guided fine-needle aspiration and tissue-core biopsy of lung
lesions in the dog and cat
M. Vignoli, G. Gnudiet, P. Laganga, M. Gazzola, F. Rossi, R. Terragni,
M. Di Giancamillo, B. Secchiero, S. Citi, A. M. Cantoni, A. Corradi.
23
Clinical efficacy of Pimobendan versus Benazepril for the treatment
of acquired atrioventricular valvular disease in dogs
C. W. Lombard, O. Jöns, C. M. Bussadori
29
UROGENTIAL SYSTEM
Intra-abdominal testicular torsion in a cryptorchid dog
G. Gradner, D. Dederichs , K.M. Hittmair
41
True hermaphroditism in six female littermates after administration
of synthetic androgens to a pregnant bitch
H. de Rooster, G. Vercauteren, K. Gortz, J. Saunders, I. Polis T. Rijsselaere
45
Urinary tract infection – A European perspective
B. Gerber
51
EXOTICS AND CHILDRENS PETS
Rabbit dentistry
A. Meredith
55
BREEDING AND GENETICS
The FECAVA symposium 2006 - healthy dog breeding
63
The value of breeding programmes
A. Indrebo
64
Segregation analysis to determine the mode of inheritance
O. Distl
71
Breeding for improved health in Swedish dogs
S. Malm
75
DIAGNOSTIC IMAGING
How to look at radiographs
C. R. Lamb
79
GENERAL
Dealing with MRSA in Companion Animal Practice
D. Lloyd, A.K. Boag, A. Loeffler
85
Pet Euthanasia - helping clients through it
G. Gadd
95
Book Reviews
99
Calendar of main European national meetings and other continuing
education opportunities
101
Secretariat or address to contact for information
104
1
The Federation of European Companion Animal Veterinary Associations (FECAVA)
FECAVA Headquarter’s address:
C/O Federation of Veterinarians of Europe
rue Defacqz, 1 B-1000 Brussels
Tel: +32 2 538 29 63 – Fax: +32 2 537 28 28
FECAVA Website: www.fecava.org
Participating Associations:
SASAP Serbia Association of Small Animal Practitioners
Director: Dr. Denis NOVAK
SSAVA Swedish Small Animal Veterinary Association
Director: Dr Alexandra VILÉN
SVK/ASMPA Schweizerische Vereinigung für Kleintiermedizin/Association
Suisse pour la Médecine des Petits Animaux
Director: Dr. Peter STERCHI
SZVMZ Slovensko Zdruzenje Veterinariev Za Male Zivali
Director: Dr. Bojan ZORKO
TSAVA Turkish Small Animal Veterinary Association
Director: Dr. Mustafa AKTAS
USAVA Ukrainian Small Animal Veterinary Association
Director: Dr. Vladimir CHARKIN
VICAS Veterinary Ireland Companion Animal Society
Director: Dr. Peter A. MURPHY
VÖK
Vereinigung Österreichischer Kleintiermediziner
Director: Dr. Silvia LEUGNER
AFVAC Association Française des Vétérinaires pour Animaux de
Compagnie
Director: Dr. Jean-François ROUSSELOT
AIVPA Associazione Italiana Veterinari Piccoli Animali
Director: Dr. Giuseppe TRANCHESE
APMVEAC Associação Portuguesa de Médicos Veterinários Especialistas
em Animais de Companhia
Director: Dr. José H. DUARTE CORREIA
AVEPA Asociación Veterinaria Española de Especialistas en Pequeños
Animales
Director: Dr. Juan Francisco RODRIGUEZ
BASAV Bulgarian Association of Small Animal Veterinarians
Director: Dr. Boyko GEORGIEV
BHSAVA Bosnia and Herzegovina Small Animal Veterinary Association
Director: Dr. Josip KRASNI
BSAVA British Small Animal Veterinary Association
Director: Dr. Ian MASON
CSAVA Czech Small Animal Veterinary Association
Director: Dr. Jiri BERANEK
CSAVS Croatian Small Animal Veterinary Section
Director: Dr. Davorin LUKMAN
DSAVA Danish Small Animal Veterinary Association
Director: Dr. Joergen MIKKELSEN
ESAVA Estonian Small Animal Veterinary Association
Director: Dr. Tiina TOOMET
FAVP
Finnish Association of Veterinary Practitioners
Director: Dr. Kaj SITTNIKOW
GSAVA German Small Animal Veterinary Association
Director: Dr.Dr. Peter FAHRENKRUG
HSAVA Hungarian Small Animal Veterinary Association
Director: Dr. Ferenc Bíró
HVMS Hellenic Veterinary Medical Society
Director: Dr. Katerina LOUKAKI
LAK
Letzebuerger Associatioun vun de Klengdeiere - Pracktiker
Director: Dr. Liz JUNIO
LSAPS Latvian Small Animal Practitioners Section of The Latvian
Association of Veterinarians
Director: Dr. Lita KONOPORE
LSAVA Lithuanian Small Animal Veterinary Association
Director: Dr. Saulius LAURUSEVICIUS
MSAVA Macedonion (Fyrom) Small Animal Veterinary Association
Director: Dr. Marin VELICKOVSKI
MVA
Malta Veterinary Association
Director: Dr. L. Vella
NACAM Netherlands Association for Companion Animal Medicine
Director: Dr. Monique MEGENS
NSAVA Norwegian Small Animal Veterinary Association
Director: Dr. Kjetil DAHL
PSAVA Polish Small Animal Veterinary Association
Director: Dr. Jerzy GAWOR
RSAVA Russian Small Animal Veterinary Association
Director: Dr. S. SEREDA
SAVAB Small Animal Veterinary Association of Belgium
Director: Dr. J. van TILBURG
SKSAVA Slovak Small Animal Veterinary Association
Director: Dr. Igor KRAMPL
Associate Associations:
ECVD
European College of Veterinary Dermatology
Contact: Dr. Dominique HERIPRET
ECVS
European College of Veterinary Surgeons
Contact: Monika GUTSCHER
ESAVS European School for Advanced Veterinary Studies (A part of the
European Association for Veterinary Specialisation (EAVS))
Contact: Dr. Hans KOCH
ESVC
European Society of Veterinary Cardiology
Contact: Dr. Chris AMBERGER
ESFM
European Society of Feline Medicine
Contact: Claire BESSANT
ESVCE European Society of Veterinary Clinical Ethology
Contact: Dr. Sarah HEATH
ESVD
European Society of Veterinary Dermatology
Contact: Dr. Chiara NOLI
ESVIM The European Society of Veterinary Internal Medicine
Contact: Dr. Rory BELL
ESVN
European Society of Veterinary Neurology
Contact: Dr. Jacques PENDERIS
ESVOT European Society of Veterinary Orthopaedics & Traumatology
Contact: Dr. Aldo VEZZONI
EVDS
European Veterinary Dental Society
President: Dr. Olivier GAUTHIER
EVSSAR European Veterinary Society for Small Animal Reproduction
Contact: Dr. Alain FONTBONNE
FECAVA Officers:
2
Dr. Ellen BJERKÅS
Dr. Andrew BYRNE
Dr. Simon ORR
Dr Johan van TILBURG
Norway
Eire
Uk
Belgium
President
Vice-President
Secretary
Treasurer
Advisor to the board:
Dr. Simon KLEINJAN
The Netherlands
Senior Vice-President
Editorial
The Federation of Veterinarians of Europe (FVE), founded in 1975, now represents 41 veterinary organisations from
36 European countries. It also looks after the interests of four key groups within the Veterinary Profession . These are ;
Practitioners (UEVP), Hygienists (UEVH), Veterinary State Officers (EASVO) and Veterinarians in Education, Research
and Industry (EVERI). Through its members FVE represents approximately 200,000 veterinarians.
FVE’s largest section is formed by the practitioners: UEVP. Its membership includes 25 national organisations of veterinary
practitioners plus two federations: the Federation of European Equine Veterinary Associations (FEEVA) and the Federation
of European Companion Animal Veterinary Associations (FECAVA). The latter is made up of 35 participating and 12
associate associations, and also produces of the excellent journal you are reading now.
FVE attaches great importance in bringing the different disciplines of the veterinary profession together. Being a small
profession, at least in numbers, we must join forces; dividing ourselves into separate groups would mean an unaffordable
loss of authority and efficiency. As veterinarians, active in different disciplines, we nevertheless all work towards the same
goals that is the health and welfare of animals and people. We contribute to the same system, and we often
face comparable problems.
Increasingly people are starting to realise that veterinarians are much more than just friendly ”Dr Herriots”, treating
sick animals. As a profession we have a much broader role to play. This is especially the case in respect to matters such as
the growing public concern about health in general, emerging diseases and zoonosis, increased international movements
of animals, responsible use of veterinary medicines, and many more issues. Veterinarians, not least companion animal
practitioners, have a key role to play in this respect. To fulfil our responsibilities it is essential that veterinarians in all
disciplines work together and form a solid network.
The challenge for an organisation like FVE, covering a broad range of activities is, of course, to keep the right balance
between all interests and to identify priorities according to the needs of the membership. In the field of companion animal
practice, FVE is, inter alia, working on items such as: veterinary medicinal products, their availability, their prescription,
distribution and administration. FVE was and still is greatly involved in the development of the current EU Medicines
Directive and its implementation. The cascade for companion animals, the implementation of which has now become
mandatory for all EU Member States, has significantly broadened the range of products that can be used legally. Another
area of activity is Veterinary training. FVE maintains a close cooperation with the European Association of Establishments
for Veterinary Education (EAEVE) and the European Board for Veterinary Specialisation (EBVS). Our goal is to ensure a
high standard of veterinary training for undergraduates, a well-defined standard of specialization and the development of a
European based system of lifelong learning. The definition of the ”Veterinary Act”, that is the total of activities that require
the intervention of a veterinarian is also a matter on which we are working. UEVP has taken the initiative to develop a draft
definition, and this is now under consultation with the other sections. Last but not least, the identification and registration
of companion animals is of concern to us. Here FVE promotes a cessation of the tattooing of animals as soon as possible and
a change to the use of universally readable transponders and databases which can communicate with each other!
These are just a few examples to illustrate the range of activities of FVE .These are of course implemented with the help of the
FVE board, working groups, secretariat together with its members, including UEVP and FECAVA. It goes without saying
that the help of countless numbers of individual companion animal practitioners has been crucial in ensuring success. I
would like to take the opportunity to thank everyone for valuable contributions given and to encourage a continuation of
this effort in the interest of the health and welfare of animals and people and also of our noble profession!
Jan Vaarten, DVM FVE Executive Director
5
The Federation of
European Companion
Animal Veterinary Associations
Welcome to the FECAVA family!
FECAVA stands for the Federation of European Companion Animal Veterinary Associations. Your
association is one of 34 Full Member Associations representing 34 European countries.
In addition to the Full Member Associations, 12 European Specialist Groups are Associate Members. A list
of Full Members and Associate Members is given on the FECAVA homepage www.fecava.org.
Through its Member Associations, FECAVA represents nearly 25 000 veterinarians in Europe. FECAVA
was founded in 1990 in Bienne (Biel) in Switzerland.
Each Member Association elects a Director to represent its interests in FECAVA. The Council of FECAVA
Directors meets twice a year.
FECAVA organises an annual European congress, as well as supporting numerous Continuing Education
courses and symposia. It holds close ties with the Union of European Veterinary Practitioners (UEVP)
and the Federation of Veterinarians of Europe (FVE). It also collaborates in areas of common interest with
other major national, European and international organisations.
FECAVA has a regularly updated website and publishes the European Journal of Companion Animal
practice (EJCAP). www.fecava.org
Benefits of membership
Through your membership of your National Association you also enjoy the following FECAVA benefits:
– You receive the FECAVA journal, the European Journal of Companion Animal Practice (EJCAP), twice
a year
– You can take advantage of discounts on publications from selected Member Associations
– You get reduction on congress fees for larger congresses throughout Europe including the FECAVA
congresses
– FECAVA works to defend the interest of all companion animal veterinarians at a European level
Once again, welcome to the FECAVA family!
Yours sincerely,
Professor Ellen Bjerkås
President
FECAVA NEWS
EJCAP - Vol. 17 - Issue 1 April 2007
FECAVA NEWS
INTRODUCING:
The first
WORLD
RABIES DAY
September 8, 2007
Did you know?
– Rabies has the highest case fatality rate
of all known infectious diseases,
approximately 55,000 people dying in
Africa and Asia annually.
– Most rabies deaths occur in children
living in countries where canine rabies
is still present – about 100 children die
of rabies every day.
– Canine rabies can be eliminated by
vaccination and stray dog control and
all human rabies deaths can be
prevented through adequate
vaccination and educational
awareness.
– Rabies is a disease for which all the
tools for control are available; what is
lacking is the motivation, commitment,
and resources for effective control in
parts of the world where the disease
continues to exert a heavy burden
Recognizing these priorities and
challenges, the Alliance for Rabies
Control (ARC) was formed as a UK
Registered charity in 2006. Its
establishment marks the start of a new
kind of initiative in the field of rabies. It is
an independent, non-profit making
organization bringing together public
and private expertise to establish a
partnership involving field personnel,
academics and a wide range of
organizations with an interest and
concern for rabies in Africa and Asia . It
hopes to reduce the impact of this terrible
disease on human and animal health.
BLUE DOG successfully
launched during Prague
Congress
FECAVA members will be pleased to hear
that the Blue Dog Project was successfully
launched during the 2006 FECAVA/
WSAVA/CSAVS congress in Prague. This
unique and exciting dog bite prevention
programme aimed at young children was
the subject of a day long symposium at
the conference. During this, Dr Kerstin
Meints, a child psychologist from
Lincoln, UK, presented the results of her
study on the efficacy of the programme
as a learning tool in children of the target
age group (3 – 6 years). This study,
funded jointly by FECAVA and the Dutch
Small Animal Veterinary Association
(NACAM), was an essential element of
the project and fortunately the results
were very positive. It was therefore with
confidence that the Blue Dog Team could
face the TV and media at the Press
Conference organized by the Czech Small
Animal Veterinary Association. This
stimulated a lot of interest and positive
feedback.
The English version is now available in
the UK through The Company of
Animals. (www.companyofanimals.co.
uk). The Blue Dog Trust is also in
negotiation with a number of FECAVA
member Associations for right to
translate and produce their own language
versions. Hopefully these should become
available during 2007. Individual
FECAVA members are encouraged to
Ray Butcher at the Blue dog launch
contact their own national association for
more details, or visit the Blue Dog
website:
www.thebluedog.org
DASVENT update Voluntary accreditation
scheme for Veterinary
Nursing
The members of the DASVENT project
met in Helsinki on the 18th & 19th of
October.
This project aims to establish a voluntary
accreditation scheme for Veterinary
Simon Berenek and his dad play the interactive video in Prague
To increase awareness, the ARC is
coordinating the WORLD RABIES DAY to
be held on September 8th 2007. This will
include the first annual ‘Run for Rabies’
in which it is hoped that veterinarians
and students worldwide will actively
participate. To find out more and sign up,
visit the website:
www.worldrabiesday.org
To find out more about the ARC, visit
their website on: www.rabiescontrol.org
So make a note in your diary and join us
on September 8th, 2007.
9
FECAVA NEWS
Nursing Education in Europe. It hoped
that this initiative will help towards
harmonizing veterinary nursing
education, improve the transparency of
qualifications and facilitate movement of
nurses as well acting as a stimulus to
develop and maintain education
standards.
The project so far has agreed a
memorandum of understanding between
the partners that defines the scope and
objectives of the project. A project specific
accreditation committee of veterinary
nursing education (ACOVENE) (www.
acovene.org ) has been established for the
duration of the DASVENT project. This
committee consists of six members drawn
from nursing course providers,
accreditation bodies and the veterinary
profession. The DASVENT project
members and ACOVENE have completed
drafts of the Accreditation policies and
procedures and also a list of
competencies.
The next stage of this project is to carry
out trial visitations to colleges
participating in the project in order to test
and evaluate the practicality and
effectiveness of the accreditation
procedures. The trial visitations will take
place between February and June of 2007.
These visitation panels will consist of
four people including a veterinary
surgeon and veterinary nurses from the
host countries’ national veterinary and
veterinary nursing associations as well as
two members of the ACOVENE
committee. The project is scheduled to
conclude in September 2007. FECAVA is a
participant in this project and holds a
position on the ACOVENE committee.
FECAVA have been asked to nominate a
veterinary surgeon in each of the
countries in the pilot scheme as listed
below to participate in the visitations.
Veterinary Nursing colleges participating
in the pilot scheme include:
FECAVA strengthens its
cooperation with UEVP
and FVE
Through membership of UEVP, FECAVA
is a member association of FVE.
At a meeting in Brussels last November
the importance of FECAVA being the
voice of all companion animal
veterinarians in Europe was again
demonstrated. The impact of the
companion animal field in the veterinary
profession is well recognised, and recent
data collated by FECAVA and presented
at the meeting demonstrated the overall
economic importance of the pet world.
One must expect an increase in matters
concerning the companion animal
veterinary profession in the years to
come. FECAVA, UEVP and FVE
acknowledge the mutual benefit of
increased cooperation between the three
bodies. The members of FECAVA are
professionals in their field, and the input
of FECAVA in matters concerning
companion animals is regularly sought.
Such matters include the education of
acknowledged veterinarians in
companion animal practice (not to be
confused with specialists), companion
animal welfare matters, the ‘veterinary
act’ to ensure the quality of veterinary
work, microchipping and education of
veterinarians and nurses.
To continue the good cooperation
between the three bodies, it has been
decided that their Boards meet on a
regular basis. Board members of UEVP
and FVE will be invited to the FECAVA
Council meetings, and, as before,
FECAVA will be represented at the UEVP
and FVE general assembly meetings.
Extra annual issue of
EJCAP
Starting in 2007 ECJAP will be published
three times annually. Previously there
were two issues in each volume. The new
third issue will be an online issue only
Kolding TS (Denmark)
SLU (Sweden)
Groenhorst College (Netherlands)
Warwickshire College (UK)
Norwegian School of Vet. Sc. (Norway)
Katholieke Hogeschool Kempen
(Belgium)
Bonapatrte Institute Paris (France)
ABIVET (Italy)
UCD (Ireland)
10
Astrid Bjerkås recently appointed sub
editor of EJCAP.
and devoted to one scientific topic each
year. This year’s issue will be devoted to
ophthalmology and the aim is to
produce an issue valuable both to
ophthalmologists and general
practitioners. Maurice Roze and Ellen
Bjerkås are the scientific editors. The
national FECAVA representatives (the
Directors) have been most helpful in
identifying topics of interest to the
different reader groups.
The FECAVA Officers and the EJCAP
editor felt it would be untenable to have a
printed third issue for only a section of
the membership, and thought the best
way forward was to produce a third issue
each year online, to be available to all
members on the FECAVA website.
Due to his present workload, EJCAP
editor Keith Davies is not able to
undertake the job of producing the third
issue himself. Astrid Bjerkås who
recently was appointed sub editor of
EJCAP will be responsible for the third
issue. Astrid was formerly the editor of
the Norwegian Veterinary Journal and
head of communications for the
Norwegian Veterinary Association.
The fact that the third issue will be online
only requires some new thinking when it
comes to finding advertisers and getting
the readers to download and read the
journal. The editor and production
subcommittee are currently investigating
ideas on how to attract sponsorship and
advertising for an online issue. Among
the possibilities are advertisements at the
end of each article, or on the website next
to the introduction of each article. It may
be possible to find one or more sponsors
for the third issue.
EJCAP
EJCAP
- Vol.
- Vol.
16 -17Issue
- Issue
2 October
1 April 2007
2006
FECAVA Policy statements
FECAVA Policy statement 5:
Animal Breeding
(adopted by FECAVA Council on 16th April 2005))
1. FECAVA recognises that companion animals may be bred under
different conditions
2. The conditions must fulfil the criteria for health and welfare of the
animals as regulated by the European Convention
3. The animal must be provided with accommodation, care and
attention, which take into account the ethological needs of the
animal in accordance with its species and breed, including adequate
opportunities for exercise.
4. Special care should be taken as to the health and mental development
of the offspring
5. Establishments which practice breeding of multiple animals should
be registered, licensed and inspected to ensure adequate standards
of welfare for each animal therein.
The following FECAVA Policy statements have been adopted:
– Mutilations in Companion Animals
– Neutering Dogs and Cats
– Permanent Identification in Companion Animals
– The Training of Veterinary Nurses
– Animal Breeding
– Cloning of Companion Animals
– The Availability of Medicines
– Organ harvesting from living companion animals
– Veterinary Education Standards
FECAVA Policy Statement 1:
Mutilations in Companion Animals
(adopted by FECAVA Council on 5th June 2004))
1. FECAVA endorses the relevant articles of the European Convention
of Pet Animals whose articles specifically prohibit the performance
of surgical procedures (including specifically the docking of dog’s
tails, the cropping of ears, de-vocalisation, de-clawing cats and defanging) for cosmetic purposes only
2. Exceptions can be made only when a veterinarian considers the
procedure in the interest of that specific animal, and is for therapeutic
purposes only
Cloning of Companion Animals
(adopted by FECAVA Council on 6th May 2006)
1. FECAVA strongly feels that it is unethical to clone companion animals
purely to provide pets with similar characteristics
2. FECAVA recognises that there may be medical and scientific
advantages obtained from cloning companion animals
3. Any such cloning procedure should be subject to the normal ethical
controls as regulated by the European Convention on the use of
animals in scientific procedures
Neutering Dogs and Cats
An effective neutering programme is considered as an essential element
of any stray animal control scheme; however the other important
elements of education, Registration and Identification should also be
considered
The Availability of Medicines
(adopted by FECAVA Council on 6th May 2006)
1. FECAVA recognizes the paramount importance of the role of
veterinarians in the relief of suffering and the promotion of welfare
of companion animals
2. To ensure this goal, FECAVA recommends that the authorisation
of medicines to relieve suffering in companion animals should be
facilitated to provide easy access throughout Europe to the medicines
vital to animal welfare
3. FECAVA reconfirms that Companion Animal medication does
not represent any risk to the human population through food
contamination.
4. FECAVA is aware of the great responsibility vested in its members to
protect and ensure the welfare of companion animals. In accepting
that responsibility, FECAVA strongly recommends the introduction of
legislation to allow for full availability of the medicines necessary to
ensure good veterinary practice for these animals
5. FECAVA recognizes the desire of the EU Parliament and Council to
achieve this goal when it stated clearly in the EU Directive 2004/28/
EC on Veterinary Medicines in section 21 of the Introduction that
‘the administrative procedures for supplying medicinal products
for pets, on the other hand, should be simplified. FECAVA urges
the governments of member states to reflect this aspiration in their
relevant regulations
Permanent Identification in Companion Animals
1. FECAVA supports the concept of Registration of dogs associated
with some form of permanent identification.
2. At the present time, FECAVA feels the identification of animals using
microchips offers the most advantages for a pan-European system
and so is the method of choice.
3. FECAVA endorses the use of the ISO Standard chip, with dual readers
that can also recognise the original FECAVA Standard microchips.
4. FECAVA would recommend the formation of a single national
database with control maintained by a non-commercial competent
authority.
5. FECAVA recognises the need for coordination of national databases
at a Pan-European level. At the current time FECAVA recognises
EuroPetNet (EPN) as the most effective means of coordinating
European national databases.
6. FECAVA recommends that the implantation of a microchip is a
veterinary procedure that should be carried out by a qualified
veterinary surgeon
7. FECAVA recommend that all dogs in Europe are identified by
microchip and registered
The Training of Veterinary Nurses
1. FECAVA recognises that national associations have different views
on the relative merits of training and employing veterinary nurses
2. FECAVA feels strongly that Veterinary nurse training should be
introduced into countries only with the full cooperation and active
participation of the national small animal veterinary association
3. FECAVA will offer support and assist in providing resource material
for those associations that request it
[1] Recipient animals will need chronic oral immunosuppression in order
to prevent organ rejection. This is a welfare cost, especially in cats.
Furthermore, inability to administer such medication may lead to failure
of the transplanted organ and unnecessary suffering.
In the case of feline renal transplantation, there is no statistically
significant difference in survival time between cats that have undergone
renal transplantation compared with those that have been treated using
medical and dietary management. There have been no published longterm studies of long-term adverse effects on uninephrectomised ‘source’
cats.
[2] For example following a road traffic accident
11
FECAVA NEWS
FECAVA Policy Statement 8
Organ harvesting from living companion animals
(adopted by FECAVA Council on 14th October 2006)
1. FECAVA strongly feels that it is unethical to perform an operation
on, or to kill, a healthy animal in order to harvest organs for the
purposes of transplantation.
2. Currently there is no compelling evidence of the animal welfare
benefits to animals receiving transplanted kidneys and other solid
organs [1]
3. Future medical, surgical and technological advances might, in theory,
enable successful transplants to be performed to the benefit of the
recipient.
4. However, in veterinary medicine source animals cannot give informed
consent for organ harvesting. This is unlike the situation in man.
Therefore it is the view of FECAVA that the only ethical option is to
harvest tissues for transplantation from animals that have died [2]
2.
3.
4.
5.
6.
FECAVA Policy Statement 9
Veterinary Education Standards
(adopted by FECAVA Council on 14th October 2006)
1. The Bologna declaration was formed with the objectives of
EJCAP - Vol. 16 - Issue 1 - April 2006
harmonizing higher education in Europe. Within the scope of this
declaration are definitions and guidelines that help define the various
levels of higher education qualifications e.g. bachelors’ degrees,
masters, doctorates etc.
Each member state has regulatory bodies that define the educational
requirements to become a registered veterinarian.
The quality of veterinary graduate education is monitored and
promoted by a voluntary accreditation process run by FVE and
EAEVE.
FECAVA is committed to supporting the above structures and
following closely the evolution of veterinary education in order to
ensure the high standard of training for veterinary undergraduates.
FECAVA believes that high quality veterinary undergraduate training
and lifelong learning programs are essential to the continued
provision of high quality companion animal healthcare and the
support of animal welfare.
It is part of FECAVA’s remit to play an active role in promotion of high
standards of veterinary education.
FECAVA Strategic planning
national associations for exchange of experience with training
programmes
– Follow-up on the DASVENT project
– Follow-up on the UEVP/EBVS CE programme
The Federation of European Companion Veterinary Associations
(FECAVA) is an “association of associations”. Its membership is made
up of European veterinary organisations, which are concerned with
companion animals. Currently there are 34 member associations and
12 affiliate member associations, representing approximately 25,000
individual veterinarians from around Europe.
4) Continue the animal welfare aspect
Means:
– FECAVA Policy Statements
– FECAVA symposia
– Involvement in welfare projects
– Promote contact between veterinarians and users (FVE, Kennel clubs,
FCI, other associations for companion animals)
Aims
The objects of FECAVA are:
– to unite, represent and promote the interests of the Companion
Animal Veterinary Profession of Europe.
– to define and promote the highest standards of practice and welfare
for companion animals.
The FECAVA strategic plan will be divided into short-term (2 years) and
long-term (5 years) planning:
5) Human-animal bond
Means:
– Promote and give support to suitable projects (e.g. the Blue Dog
Project and similar)
– Develop and disseminate information material on the significance of
pet ownership (external help)
Long-term:
Short term:
1) Establish FECAVA as a policy-creating body setting
standards for veterinary matters related to companion animals
Means:
– FECAVA should work with all relevant bodies both within and outside
the veterinary profession e.g. FVE, UEVP, FEEVA, etc
– FECAVA should be proactive in identifying issues of importance for
the companion animal veterinary profession
– Foster a closer relationship with FVE
– Establish a relationship with the research administration of the EUCommission
– Gather information on the economic and social significance of
companion animal ownership to be developed and disseminated
(External help)
– Promote widespread microchip identification
Establish a accepted and approved strategic plan to allow FECAVA to
achieve the above long-term aims
Development of a Strategic plan
1) Channels of communication
A. Increase contact with each Director, in order to ensure
that our activities fulfil the needs of and are approved by the
associations
Means:
– Direct e-mail contact for rapid dissemination and gathering of
information through the membership
– Board and Director representation at national meetings
B. Increase the sense of “ownership” perceived by the national
associations.
Means:
– Achieved by more personal contact – ask for the view of each single
Director
2) Continue to develop the profile of EJCAP
Means:
– Develop issue 3
– Plan for new EJCAP Editor Manager
C. Establish the strengths and weaknesses of FECAVA.
What are the key strengths of the Federation?
How can the weaknesses be defined – how can they be met?
Means:
– Help from a professional consultant on communication and
management training
3) Support, co-ordinate and formulate continuing education
projects for veterinarians and technicians
Means:
– Encourage nurse training and stimulate communication between
12
EJCAP
EJCAP
- Vol.
- Vol.
16 -17Issue
- Issue
2 October
1 April 2007
2006
2) CE activities
A. EJCAP
Continue to finalise design following change to new printer, including
cover design, article layout etc
Improve distribution by encouraging direct mailing to members
Encourage associations to receive journals for all their members
Investigate the possibility of indexing of the journal
Encourage good-quality directly submitted material.
Plan for 3rd trial issue
C. CE-courses
Means:
– Financial help for associations to arrange CE courses
– Co-operation between countries
– Help in finding lecturers
D. Recognition of CE
Means:
– Promote the need for continuing education of a suitable level
– Dissemination of CE material using modern communications tools
B. Congresses
Encourage national associations to arrange the annual FECAVA
congress
3) Promotion of FECAVA to the Profession
Means:
– Actively promote FECAVA at national and international congresses
and if possible, address the delegates
– Include FECAVA logo and name whenever possible
– Establish a closer relationship with students’ associations
Means:
– Help to national associations in promoting congresses
– Encourage directors to make it known to their members.
– Help in finding lecturers.
– Review the FECAVA Congress Protocol
4) Development of FECAVA Secretariat
Means:
– Develop a plan for professional secretariat and management
support
– Review the location of such services
WSAVA Activities
From Dr Walt Ingwersen WSAVA Editor
WSAVA/FECAVA /CSAVA
2006 Congress Highlights
Spectacular weather and the historic city
of Prague welcomed 2,996 delegates
representing 72 countries during the 31st
WSAVA/12th FECAVA/14th CSAVA
Congress held from October 11-14, 2006.
The top five countries in terms of
attendance were Czech Republic, United
Kingdom, USA, Canada, and Austria. The
continuing education (CE) programme
comprised 268 lectures (including 6
State-Of-The-Art Lectures) representing
29 different disciplines/specialties and
given by 93 speakers from virtually every
continent of our planet. This was
complemented by 132 poster
presentations and several Pre-Congress
meetings that included the Veterinary
Emergency and Critical Care Society
(VECCS), the European Society of
Veterinary Cardiology (ESVC), the
International Veterinary Ear, Nose, and
Throat Association (IVENTA), the
International Elbow Working Group
(IEWG), EuroPetNet (EPN), and the
International Veterinary Editors Meeting.
The Congress was supported by Prime
Partner Hill’s, Partners Bayer Animal
Health, Intervet, and Purina, as well as
Sponsors Iams, Merial, The North
American Veterinary Conference,
Schering Plough Animal Health, and
Storz together with a total of 98
exhibitors within the Exhibition Hall.
Evenings were spent meeting old friends
and making new ones at a variety of
lively social events, including the
Opening Ceremonies, the Czech
Medieval Party at the historic Drevcice
Citadel, and the Gala Evening, held at
Prague’s famous Municipal House. And
all of this took place with the back drop
of historic Prague, the Golden City or
100-Spired City; overall, the Prague
Congress was a tremendous event that
will leave attendees with many fond and
lasting memories.
2006 WSAVA Award
Winners
WSAVA WALTHAM International
Award for Scientific Achievement
Dr. Dale E. Björling, Professor and Chair
of the Department of Surgical Sciences at
the University of Wisconsin, School of
Veterinary Medicine.
WSAVA WALTHAM International
Award for Service to the Profession
13
Dr. Colin F. Burrows, Professor of
Medicine and Chair of the Department of
Small Animal Clinical Sciences at the
University of Florida, College of
Veterinary Medicine.
WSAVA Iams Saki Patsaama Award
Dr. Darryl L. Millis, Professor of
Orthopedic Surgery at the University of
Tennessee, College of Veterinary
Medicine.
WSAVA Hills Excellence in Veterinary
Healthcare Award
Dr. Eric Teske, Department of Clinical
Science, Companion Animals, Utrecht
University.
WSAVA Assembly Meeting
WSAVA President Dr. Larry Dee
welcomed the Assembly members after a
17-month hiatus since the last assembly
meeting in Mexico City on May 10, 2005.
He provided assembly members with
updates from a very active WSAVA
leadership, including the Executive Board
and various committees. Highlights
included:
– A reconstituted Hereditary Defects
Committee under the Chairperson of
Dr. Urs Giger from the University of
Pennsylvania
– Plans for renewal & re-ratification of
the WSAVA Convention for the
FECAVA NEWS
meeting in Dublin, the renal
standardization project which was
currently undergoing negotiations with
sponsors and expected to start soon,
and various other projects under
consideration
The assembly members voted in favour of
accepting one new full member
associations – the Guangdong Small
Animal Veterinary Association
(GDSAVA) from China. Additionally,
Geneva, Switzerland was chosen as the
site for the 2010 WSAVA Congress.
Future Congresses
Newly elected WSAVA Executive Board members are (pictured left to right) Drs. Terry
Lake (Vice President; Canada), David Wadsworth (President Elect; UK), Brian Romberg
(President; South Africa), Anne Sorensen (Honorary Secretary; Denmark), Larry Dee
(Immediate Past President; USA), Luis Tello (Executive Board Member; Chile), and Jolle
Kirpensteijn (Honorary Treasurer; Netherlands).
Prevention of Cruelty to Animals
– Consideration is being given to convert
the WSAVA Handbook to a web-based
rather than hard-copy resource
– Updates on the various standardi-
zation projects were given including
the successful WSAVA Hepatic
Standards textbook published by
Elsevier, the likely completion of the GI
Standards project by the next Assembly
Sydney Convention Centre, Sydney,
Australia – August 19-23, 2007
As Di Sheehan, Chair of the Sydney
Congress organizing Committee so aptly
puts it “Just how long can you keep
saying ‘one day I’ll go to Sydney,
Australia’?” Well, 2007 is the year!
Located in the scenic Sydney enclave of
Darling Harbour, the Organizing
Committee have already laid the
foundation for another memorable
Congress with world-class CE speakers
and a number of social events that
highlight the wonders of the “land down
under”. So mark your calendars and visit
the Congress 2007 website at www.
wsava2007.com for more information.
UEVP NEWS
From Marco Eleutri, Vice-President, UEVP
Alternative medicine: the
new offshore paradise of
the Veterinary Profession?
For many years the Veterinary Profession
in Europe has been involved in
stimulating and harmonizing the
promotion of quality professional
services between member states.
The Code of Good Veterinary Practice,
the Continuing Education Postgraduate
Programme and the National Veterinary
Surgeons Acts are some examples of this.
In recent years, complementary (or
alternative ) medicine has become more
and more popular both in human and
veterinary medicine. This definition
covers a wide variety of forms of
treatment, some of them are based on
scientific evidence as is the case in
conventional medicine, whilst others
operate in a much greyer borderline area.
alternative medicine is incomplete or
unclear in almost all member states
This leads to confusion and penalises
those working in the correct way.
For these reasons UEVP thinks it
essential to open discussion between
member states on the rules that should
apply to this form of medicine.
Marco Eleuteri
In many cases those working in these
fields have neither graduated or have a
recognized diploma. Clients often have
no guarantee of the quality of work.
A number of training courses about
which little or nothing is known have
developed throughout Europe. The
legislation governing the practice of
14
Alternative Medicine must be governed
by statue and must only be performed
only by a veterinarian.
Treatments, also, if undertaken by a nonveterinarian (with a recognised diploma),
should be done under the control and
responsibility of a Veterinarian.
Not to recognise the problems relating to
this expanding market will be
detrimental to the veterinary profession
as a chance to control these alternative
methods will be lost.
REPRINT PAPER (UK)
A retrospective study of clinical
findings, treatment and outcome in
143 dogs with pericardial effusion
M. Stafford Johnson (1), M. Martin (1),S. Binns(2) , M. J. Day(2)
SUMMARY
A retrospective study of 143 dogs with pericardial effusion is presented, including a statistical analysis of survival
time. Cases were classified into those in which a mass was seen on echocardiography (echo-positive) and those in
which no mass could be identified (echo-negative). Forty-four dogs were echo-positive and 99 were echo-negative.
The median survival time (MST) was 1068 days for echo-negative dogs and 26 days for echo-positive dogs. Dogs with
a history of collapse were more likely to present with a mass on echocardiography. Those presenting with collapse
had an MST of 30 days compared with 605 days for those without collapse. Echo-negative dogs tended to present
with ascites and generally had a larger volume of pericardial effusion. The median survival for dogs presenting
with ascites was 605 days compared with 45 days for those without ascites. Among echo-negative dogs, 64 per cent
had a relapse of their effusion. Subtotal pericardiectomy was performed in 31 echo-negative dogs. The procedure
had a perioperative mortality of 13 per cent but provided a favourable long-term prognosis. Dogs undergoing
pericardiectomy had a median survival of 1218 days compared with 532 days for those not undergoing surgery.
and clinical signs. Pericardiectomy is recommended in cases of
recurrent IP and prolonged survival after pericardiectomy has
been documented in affected dogs (Aronsohn and Carpenter
1999). Following pericardiectomy, survival times in dogs with
neoplastic pericardial disease are generally reported to be
much shorter than those with non-neoplastic disease (Cobb
and Brownlie 1992, Kerstetter and others 1997). However, in
dogs with heart-base tumours, prolonged survival has been
documented following pericardiectomy (Vicari and others 2001,
Ehrhart and others 2002).
This retrospective study details the signalment, presenting
clinical signs, results of diagnostic investigations and a statistical
analysis of survival in 143 dogs with pericardial effusion.
This paper originally appeared in:
Journal of Small Animal Practice* (2004)
45, 546–552
Introduction
Pericardial effusion is well recognised in the dog, with the
most common causes being neoplasia or idiopathic pericarditis
(IP). Signalment, presenting signs and clinical findings have
been published previously (Gibbs and others 1982, Berg and
Wingfield 1984).
Echocardiography is the most useful non-invasive diagnostic
procedure for differentiating the aetiology of effusion but
pericardiectomy, with direct examination of the heart and
histological examination of the pericardium, may be required to
reach a definitive diagnosis (Fruchter and others 1992, Dunning
and others 1998).
Pericardiocentesis is required for the relief of cardiac tamponade
Materials and Methods
The case records of all dogs diagnosed with pericardial effusion
between January 1994 and January 2002 at the Veterinary
Cardiorespiratory Centre, Kenilworth, and the records of cases
(1) Veterinary Cardiorespiratory Centre, 43 Waverley Road, Kenilworth, Warwickshire, GB-CV8 1JL. E-mail: [email protected]
(2) School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol , GB- BS40 5DU
* Presented by BSAVA (United Kingdom)
15
A retrospective study of clinical findings, treatment and outcome in 143 dogs with pericardial effusion - M. Stafford Johnson
from other referral centres in the UK that submitted pericardial
tissue or fluid for analyses during a previous study (Day and
Martin 2002), were retrospectively reviewed. The records
were examined for signalment, history, physical examination,
diagnostic tests performed, number of pericardiocenteses
performed and whether pericardiectomy was undertaken.
Follow-up information on the outcomes was obtained primarily
by telephone contact with the owners and the referring
veterinary surgeons. Follow-up examinations were performed
where feasible.
Only dogs with pericardial effusion due to cardiac neoplasia,
infectious pericarditis or suspected idiopathic pericarditis were
included. Cases with pericardial effusion secondary to other
recognised causes (for example, dilated cardiomyopathy,
mitral valve disease, hypoproteinaemia or congenital
pericardioperitoneal hernia) were excluded.
All dogs underwent a routine physical examination.
Electrocardiography was performed in right lateral recumbency
and thoracic radiographs were obtained in dorsoventral
and right lateral views, as described by Suter and Lord
(1984). Echocardiography was performed before and after
pericardiocentesis from standard right and left parasternal
positions on the dependent side, according to the protocol
described by Boon (1998). Blood samples for haematology,
biochemistry and electrolytes were obtained prior to sedation
or pericardiocentesis. Pericardium obtained via pericardiectomy
was submitted for histopathological examination in 10 per cent
neutral-buffered formalin.
Pericardiocentesis was performed under sedation with
acepromazine (ACP injection 2 mg/ml; Novartis) at a dose
of 0·01 to 0·03 mg/kg combined with morphine (10 mg/ml
morphine sulphate; Martindale) at a dose of 0·3 to 0·5 mg/kg,
administered intramuscularly. Local anaesthesia was achieved
by injection of lignocaine HCl (2 per cent) into the entry site.
Pericardiocentesis was usually performed with the patient in
left lateral recumbency. A pericardiocentesis catheter set (Cook
Australia) was used in the cases examined at the Veterinary
Cardiorespiratory Centre.
Surgery involved subtotal pericardiectomy performed via a lateral
thoracotomy (Orton and Gaynor 1995) and was undertaken
in cases of recurrent IP or constrictive pericardial disease. In
general, dogs with a mass detected on echocardiography did
not undergo pericardiectomy. However, questionable cases
underwent exploratory thoracotomy and in some cases a mass
was confirmed at surgery.
For the purpose of statistical analysis, cases were classified into
those in which a mass was seen on echocardiography (echopositive), and those in which no mass could be identified
(echo-negative). Constrictive pericardial disease was identified
in cases in which a small quantity of effusion, evident on
echocardiography, was seen to be causing significant cardiac
tamponade (Thomas and others 1984).
Table 1. List of cases by breed and numbers of
each breed affected
Golden retriever
German shepherd dog
St Bernard
Crossbreed
Labrador
Newfoundland
Springer spaniel
Boxer
Staffordshire bull terrier
Rottweiler
Jack russell terrier
Border collie
Cocker spaniel
Dobermann
Flat-coated retriever
English bull terrier
Bulldog
Rhodesian ridgeback
Weimaraner
Saluki
Great Dane
Lurcher
Cavalier King Charles spaniel
Italian spinone
Airedale
Bull mastiff
Bearded collie
Chesapeake bay retriever
Japanese akita
47
19
11
10
9
8
3
3
3
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
that were lost to follow-up or that were alive at the end of the
study period were right censored for statistical analysis. Cases
that were euthanased due to pericardial disease were classified
as having died of pericardial disease. Although the limitations of
this method of classification are acknowledged (Hosgood and
Scholl 2001), the proportion of euthanased animals in the study
sample was so high that censoring these observations frequently
resulted in failure to calculate median survival times (Binns and
others 2003).
Statistical analysis was carried out using Stata version 7·0 (Stata
Corporation). Comparison of variables between echo-negative
and echo-positive cases was carried out using Kruskal-Wallis
methods and chi-squared tests for continuous and categorical
variables, as appropriate. The median survival time (MST), the
time at which 50 per cent of dogs in the category were still
alive, and 95 per cent confidence intervals (CI) for the MST were
calculated.
Twenty-nine variables related to signalment, clinical signs and
examination findings were evaluated for their usefulness as
prognostic indicators for dogs with pericardial effusion, using
univariable Kaplan-Meier analysis and calculation of univariable
hazard ratios (giving the relative risk of survival) (Lee and Go
1997). Forward stepwise Cox proportional hazards regression,
including a test of the proportional hazards assumption for the
Statistical analysis
It was assumed that all mortality was related to pericardial
disease for the purpose of this study. Analysis carried out using
right censoring for dogs dying or euthanased due to other
causes gave very similar results (Binns and others 2003). Dogs
16
Table 2. The four most commonly affected pure breeds by diagnosis and age at presentation
Breed
Echo-negative
Total
Echo-positive
Mean age in years at
presentation (range)
Number of
cases
Mean age in years at
presentation (range)
Number of
cases
Golden retriever
17
8·5 (5-13)
40
9·4 (7-13)
7
German shepherd dog
19
7·3 (1·5-11)
10
9 (8-11)
9
St Bernard
11
2·3 (0·6-6)
11
–
0
Labrador
9
8·1 (4-12)
7
10·5 (9-12)
2
final model, was used to evaluate the relationship of probability
of survival to several variables simultaneously (Lee and Go 1997).
A statistically significant association was taken to be one with a
P value of less than 0·05.
Table 3. Presenting signs and clinical findings in 143
cases of pericardial effusion
Sign
Results
Diagnosis, signalment and age at presentation
The total number of dogs with pericardial effusion included in
this retrospective study was 143; 115 were from the Veterinary
Cardiorespiratory Centre and 28 from other referral centres.
Forty-four dogs were diagnosed as echo-positive, while 99 were
echo-negative. One of the echo-negative dogs was diagnosed
with septic pericarditis. Eleven dogs were found to have
constrictive pericardial disease. Of these, 10 were echo-negative
and one was echo-positive.
Of the entire population of 143 cases, 47 were Golden retrievers
(33 per cent), 19 German shepherd dogs (13 per cent), 11 St
Bernards (8 per cent), 10 crossbreeds (7 per cent), 9 Labradors
(6 per cent) and 8 Newfoundlands (5·5 per cent) (Table 1).
The mean age at presentation for Labradors was 8·1 years (range
four to 12 years); 8·5 years (range five to 13 years) for golden
retrievers; 7·3 years (range 1·5 to 11 years) for German shepherd
dogs; 5·7 years (range four to nine years) for Newfoundlands;
and 2·3 years (range eight months to six years) for St Bernards
(Table 2). Echo-positive dogs generally presented at an older
age than those that were echo-negative. For example, German
shepherd dogs that were echo-positive had a mean age of nine
years (range eight to 11 years) while echo-negative dogs of this
breed had a mean age of 4·2 years (range 1·5 to seven years).
Among the Golden retrievers, corresponding figures were 9·4
years (range seven to 13 years) and 8·5 years (range five to 13
years).
From a total of 47 Golden retrievers, 40 (81 per cent) were echonegative. The remaining nine (19 per cent) were echo-positive.
Among German shepherd dogs (n=19), 10 (53 per cent) were
echo-negative and nine (47 per cent) were echo-positive. All of
the 11 St Bernards were echo-negative. Among the Labradors,
(n=9), seven (78 per cent) were echo-negative and two (22 per
cent) were echo-positive.
One echo-negative dog was diagnosed with septic pericarditis
at postmortem examination. Of the remaining 98 echo-negative
dogs, 78 were male (80 per cent) and 20 (20 per cent) were
female. Of the 40 echo-negative Golden retrievers, 36 (90 per
cent) were male and four (10 per cent) were female. Of the
echo-positive dogs, 24 were male and 20 female.
Number of cases (%)
Muffled heart sounds
106 (74)
Weakness, lethargy
105 (73)
Ascites
97 (68)
Exercise intolerance
82 (57)
Weak pulse
51 (36)
Pallor
44 (31)
Dyspnoea
40 (28)
Collapse
33 (23)
Coughing
33 (23)
Vomiting, diarrhoea
23 (16)
Polydipsia
17 (12)
Clinical signs
The clinical signs evident at presentation are summarised in
Table 3. The most common were muffled heart sounds (74 per
cent), weakness or lethargy (73 per cent), ascites (68 per cent)
and exercise intolerance (57 per cent). Collapse was defined as
the adoption of lateral or sternal recumbency following exercise
or exertion.
Fifty-one percent of dogs that were echo-positive presented
with collapse. In contrast, 17 per cent of echo-negative dogs
presented with collapse (P<0·001). Ascites was noted in 19 of
44 echo-positive dogs (43 per cent) and 78 of 99 (79 per cent)
dogs that were echo-negative (P<0·001). Coughing was noted
in 33 of 143 cases (23 per cent) with a similar prevalence among
echo-positive and echo-negative dogs.
Electrocardiographic findings
Electrocardiography was performed in 64 cases. Electrical
alternans was documented in 24 of these cases (37 per cent). An
R wave amplitude of less than 0·5 mV in lead II was documented
in 11 cases (17 per cent), although 32 cases (50 per cent) had
an R wave amplitude of less than 1 mV. Ventricular premature
beats were documented in 11 cases (17 per cent) and three of
these had runs of ventricular tachycardia (VT). Atrial fibrillation
was present in four cases (6 per cent) and supraventricular
premature complexes in two cases (3 per cent).
All four cases of atrial fibrillation were documented in echonegative cases and all three dogs with VT were found to have a
mass on echocardiography.
17
FIG 1. Kaplan-Meier curve for echo-negative dogs, which did or
did not have pericardiectomy
FIG 2. Kaplan-Meier estimates of survival time, by presence or
absence of a mass on echocardiography (data set 3)
Radiographic findings
A total of 90 dogs underwent thoracic radiography.
Cardiomegaly with a globular cardiac silhouette was evident in
78 cases (87 per cent) and pleural effusion was present in 31
cases (34 per cent). In one case there was evidence of a large
cardiac mass, and pulmonary masses were seen in two cases.
These were suspected metastases from a cardiac mass visualised
on echocardiography.
eight dogs three times, four dogs four times and two dogs
underwent surgery on six occasions.
The volume of fluid removed was recorded for 80 cases in which
complete drainage was considered to have been achieved. The
volume of effusion removed from echo-negative dogs (excluding
those with restrictive pericardial fibrosis) had a median of 730
ml (interquartile range 400 to 900 ml) with eight dogs having
volumes in excess of 1000 ml. In comparison, the median volume
removed from echo-positive dogs was 498 ml (interquartile
range 250 to 600 ml), with only one dog having an effusion in
excess of 1000 ml.
Echocardiographic findings
Unequivocal evidence of a mass on echocardiography was noted
in 42 of 143 cases (29 per cent). In addition, two cases that
were suspected to have a cardiac mass on echocardiography
underwent an exploratory thoracotomy which confirmed the
presence of neoplasia. Ninety-nine cases (69 per cent) were
echo-negative.
One case presented with unusual findings of multiple linear
densities in the pericardium and a distorted pericardial space.
This dog was shown to have septic fibrinous pericarditis at
postmortem examination (Stafford Johnson and others 2003).
Surgery
Pericardiectomy was performed in 31 cases and the pericardium
was submitted for histopathological examination in all of
these cases. All were diagnosed with idiopathic pericarditis on
histological examination. An additional two dogs that underwent
exploratory thoracotomy were found to have masses and were
euthanased at the time of surgery.
Perioperative death occurred in four dogs (13 per cent). This
involved sudden death and occurred in four dogs within five
days of surgery (two St Bernards and two great Danes). One dog
was euthanased after seven days because of progressive renal
failure. Persistent pleural effusion developed postoperatively in
two of 31 dogs (6 per cent) and these dogs were euthanased at
three and 12 weeks after surgery.
Haematological and biochemical findings
Blood samples were obtained in 85 cases. Anaemia with an
haematocrit below 37 per cent was found in 34 cases (40 per cent).
This was classified as non-regenerative or poorly regenerative in
all cases. There was no difference in the prevalence of anaemia
between echo-positive and echo-negative cases (P=0·1). Total
protein concentrations below 53 g/litre were found in 19 cases
(22 per cent). Albumin concentrations below 24 g/litre were
found in 14 cases (16 per cent) and globulins below 26 g/litre
were found in 38 cases (45 per cent). Again, no difference in
these parameters was apparent between echo-positive and
echo-negative dogs (P=0·5 and P=0·9 for albumin and globulin,
respectively).
Survival analysis
Most dogs in which neoplasia was diagnosed were euthanased
rather than being allowed to die naturally. Only two of the 40
dogs in which a mass was diagnosed reached the end point
of natural death, while 16 were euthanased. Exclusion of
euthanased animals from the current data set was therefore
not attempted as this would have resulted in deletion of half
the observations. When euthanased dogs were right censored
rather than being considered to have reached the end point, the
analysis lacked power. When euthanased dogs were treated as
reaching the end point a more complete analysis was possible.
The results of the univariable Kaplan-Meier analysis are
presented in Table 4. One hundred and twenty-five dogs had
Pericardiocentesis
Pericardiocentesis was performed in 143 dogs. Of the 44 echopositive dogs, 32 underwent pericardiocentesis once, eight dogs
twice and four dogs three times. Of the 99 echo-negative dogs,
54 dogs underwent pericardiocentesis once, 31 dogs twice,
18
sufficient data available for survival analysis. Eighty-one of these
125 dogs reached the end point of death or euthanasia due to
pericardial disease.
Several clinical signs were associated with a significant difference
in prognosis. Dogs that presented with collapse had an MST
of 30 days (95 per cent CI 20 to 162 days) and those without
collapse had an MST of 605 days (95 per cent CI 242 to 1205
days, P<0·001). In contrast, dogs that presented with ascites
had a longer MST of 605 days (95 per cent CI 296 to 1218 days)
compared with those without: 45 days (95 per cent CI eight to
115 days, P<0·001).
Dogs that were echo-positive for a mass survived for a shorter
period than those without. MST in dogs with a mass was 26
days (95 per cent CI seven to 60 days), whereas for those
without it was 1068 days (95 per cent CI 532 to 1824 days,
P<0·001). Echo-positive dogs were more likely to present with
collapse (odds ratio 8·8, 95 per cent CI 3·4 to 23·2, P<0·001).
Echo-negative dogs were more likely to have ascites (odds ratio
5·13, 95 per cent CI 2·2 to 12·0, P<0·001).
The 31 echo-negative dogs undergoing subtotal pericardiectomy
had an MST of 1218 days (95 per cent CI unobtainable), whereas
the MST for those that did not have surgery (n=68) was 532
days (95 per cent CI 379 to 1205 days, P=0·01) (Fig 1).l
Cox proportional hazards regression analysis showed that
the diagnostic category (echo-positive or echo-negative) was
important in determining survival (Fig 2). In addition, the
presence of ascites and collapse on presentation remained
significant prognostic indicators.
Discussion
Problems in the application of methods of survival analysis
in companion animal epidemiology have been described by
Hosgood and Scholl (2001) and Binns and others (2003).
Observations from euthanased animals may be deleted from the
data set, right censored at the time of euthanasia (right censoring
occurs when survival time is known only to exceed a certain
value [Leung and others 1997]) or included as cases meeting the
end point criterion (‘failures’). The problem is that euthanasia is
not an end point determined by disease pathology alone, but by
a complex interplay of factors relating to the disease, the animal,
financial constraints, the owner and the veterinary surgeon. This
gives rise to a form of informative censoring. All the common
methods of accounting for euthanased animals will result in
biases in the estimation of survival time.
These problems are compounded by other common features
of longitudinal data sets: interval censoring (animals are not
continuously observed, but are only examined at certain
Table 4. Results of univariable Kaplan-Meier survival analysis and log-rank tests on 125 dogs,
using the end point of death or euthanasia (n=81 cases)
Variable
Number
Median survival time
(95% CI) in days
Female
15
45 (2)
Female neutered
20
100 (13-421)
Male
70
532 (180-1205)
Male neutered
20
184 (9)
Collapse
30
30 (20-162)
No
95
605 (242-1205)
Ascites
91
605 (296-1218)
No
34
45 (8-115)
Arrhythmia
15
62 (4)
45
1205 (180-2793)
1
74
115 (60-414)
2
34
532 (162-1218)
3
12
498 (80)
4
4
1205 (–)
6
1
–
No
Hazard ratio
(95% CI)
P value
(log-ranktest)
0·061
2·74 (1·7-4·4)
0·0002
0·26 (0·2-0·4)
<0·0001
1·7 (0·7-3·6)
0·083
Number of drainages:
Pericardiectomy
32
1218 (631)
93
151 (81-379)
No
87
1068 (532-1824)
Yes
29
26 (7-60)
8
28 (1-232)
No
0·088
0·25 (0·1-0·5)
0·0001
Echo mass:
Suspicious
<0·0001
19
intervals); a proportion of animals is generally lost to followup; animals may die or be euthanased due to other diseases; or
the cause of death or euthanasia may be unknown. Using this
data set, survival analysis was performed using three different
classifications of the end point (Binns and others 2003). When
euthanased animals were treated as having reached the end
point, a more complete analysis was possible and, unlike the
data sets analysed by Hosgood and Scholl (2001), the ranking
of the estimates of median survival time for strata tended to be
conserved whichever data set was used.
In this study, all dogs that died or were euthanased were
assumed to have died due to pericardial disease and it is very
likely that few died or were euthanased of unrelated causes.
This is supported by the observation that analysis of the same
data using right censoring for dogs dying or being euthanased
due to other or unknown causes led to very similar results (Binns
and others 2003). Additionally, Schwarz and others (1991)
indicated that animals dying of unknown causes may be included
with those reaching the end point if it is suggested by clinical
considerations that death is likely to have been associated with
the disease in question.
The Golden retriever was commonly represented in this
retrospective study and other breeds frequently diagnosed
were the Labrador, German shepherd dog, St Bernard and
Newfoundland. Although these data were not analysed in
comparison with a normal hospital population, it is of note that
the observed breed distribution was similar to those reported
in several previous reports from different geographical centres
(Gibbs and others 1982, Cobb and Brownlie 1992, Dunning
and others 1998, Aronsohn and Carpenter 1999). The age of
onset varied among breeds with St Bernards presenting at a
younger age (mean age 2·6 years) when compared with the
other commonly represented breeds.
The authors believe that the majority of dogs with no mass
evident on echocardiography (echo-negative) had idiopathic
pericarditis. Echo-negative dogs were more likely to be male,
while echo-positive dogs showed no such predisposition. In
particular, echo-negative male Golden retrievers were overrepresented compared with females. Some previous studies
have found a similar male bias towards idiopathic pericarditis
(Matthiesen and Lamerding 1983, Berg and Wingfield 1984)
while others have not (Stepien and others 2000).
The outcome varied among the breeds. The majority of Golden
retrievers and all of the St Bernards were echo-negative.
Almost 50 per cent of German shepherd dogs with pericardial
effusion had a mass detected on echocardiography. Therefore,
the prognosis would appear to be guarded when pericardial
effusion is diagnosed in dogs of this breed.
Dogs presenting with a history of collapse were more likely
to present as echo- positive than echo-negative in this study.
This may be because haemorrhage associated with neoplasia
caused rapid expansion of the pericardial sac and acute onset
of tamponade (Dunning and others 1998). IP may cause more
gradual accumulation of pericardial effusion which allows the
pericardial sac time to expand (Gibbs and others 1982), and this
may explain the larger volume of effusion in IP versus neoplastic
cases. A previous study reported an incidence of 12 per cent of
collapse in dogs presenting with heart-base masses, although
not all of these showed pericardial effusion (Vicari and others
2001). In the present study, over 50 per cent of cases that were
echo-positive presented with a history of prior collapse.
Collapse was associated with a reduced MST while ascites
predicted a longer MST. Again, this probably reflects the nature
of the underlying effusion, with echo-positive dogs more likely
to show collapse and echo-negative dogs more likely to have
ascites. However, the presenting signs remained as independent
predictors of survival in the Cox regression model, which also
included the results of echocardiography, suggesting that other
effects are present.
Coughing, which is not conventionally considered a feature of
pericardial effusion, was noted in 23 per cent of cases. This
compares with an incidence of 18 per cent described in the
series reported by Stepien and others (2000). Coughing may
occur due to a greatly distended pericardial sac pressing on
the airways (Gibbs and others 1982, Bjorling and Keene 1989).
In several cases, coughing was noted by the owner to be the
first sign of a recurrence of pericardial effusion following prior
pericardiocentesis.
Almost two thirds (64 per cent) of echo-negative cases relapsed,
while all dogs with neoplasia relapsed. It would seem advisable
therefore to inform owners that relapse is likely even in the
absence of a mass on echocardiography. The median period
for relapse of echo-negative dogs was 16 weeks. However, this
varied widely (range one to 250 weeks).
Electrocardiographic examinations confirmed the findings of
earlier studies that electrocardiography has a low sensitivity in
the diagnosis of pericardial effusion. R wave amplitude was in
the low normal range (below 1 mV) in 50 per cent of cases. This
compared with a 57 per cent incidence mentioned in another
report (Bonagura 1981) and 73 per cent in a second paper
(Stepien and others 2000). Electrical alternans was noted in 37
per cent of cases, which compares with an incidence of 64 per
cent reported by Bonagura (1981) and 20 per cent incidence
reported by Cobb and Brownlie (1992). Frequent ventricular
premature beats or VT unassociated with pericardiocentesis or
surgical intervention were seen in dogs with neoplasia, although
the numbers involved were small (n=3).
Thoracic radiology was useful in the diagnosis of pericardial
effusion, with 87 per cent of cases demonstrating cardiomegaly
and 34 per cent of cases having pleural effusion. Radiology was
an insensitive means of distinguishing the cause of effusion,
although the technique was occasionally useful in the detection
of pulmonary masses, which might represent metastases from
a primary cardiac tumour. To assess the presence of a mass on
echocardiography it was essential to perform the examination
from right parasternal, left cranial and caudal parasternal
positions both before and after pericardiocentesis to allow
maximum visualisation of all cardiac regions, particularly the
heart base (Vicari and others 2001). Right auricular masses in
particular were best assessed prior to pericardiocentesis. The
right atrium and particularly the right auricle were assessed
in every case and this involved obtaining non-standard views,
particularly to visualise the auricle. This was considered necessary
in order to diagnose neoplasia, which frequently involves the
right atrium or auricle (Fruchter and others 1992).
Anaemia was diagnosed in 40 per cent of the cases in which
a complete blood count was performed. This was presumably
due to the anaemia of chronic disease as it was non- to poorly
20
regenerative in all cases. Mild anaemia was noted in 28 per cent
of cases of pericardial effusion in a study by Berg and Wingfield
(1984) and in five of 22 cases reported by Kerstetter and others
(1997).
Hypoproteinaemia involving either hypoalbuminaemia or
hypoglobulinaemia were commonly noted in the series reported
here and has been noted in other reports (Matthiesen and
Lammerding 1983, Kerstetter and others 1997). This may be
associated with congestive heart failure or effusions into body
cavities, among other causes, and is not specific for pericardial
effusion (Bush 1991).
The difficulties of detecting neoplasia on echocardiography
have been mentioned previously (Bouvy and Bjorling 1991,
Fruchter and others 1992, Orton and Gaynor 1995). A definitive
diagnosis of idiopathic pericarditis can only be made through
histopathology, although recent studies have found that
mesothelioma and IP may be difficult to distinguish even on
histology. Mesotheliomas are also difficult to diagnose on
routine echocardiography due to the absence of a mass effect
(Stepien and others 2000). Histology was performed on only
31 cases in this series, all of which were classified as IP. Some
dogs categorised as echo-negative showing short survival
times may have had neoplasia which was not apparent on
echocardiography.
Neoplasia was diagnosed by finding a mass on echocardiography.
Echocardiography cannot differentiate between neoplasia,
granulomas or thrombi in most cases, although the latter two
conditions are considered rare (De Madron and others 1987)
and therefore all echo-positive dogs were categorised as having
neoplasia. There was no attempt made to differentiate between
different forms of neoplasia in this study. Histopathology was
not performed in these patients.
In the series reported here, cases showing masses on
echocardiography, whether heart-based or not, were given poor
prognoses and pericardiectomy was not performed. However,
a recent study reported prolonged survival times in dogs with
heart-base tumours (Ehrhart and others 2002), although not
for atrial haemangiosarcomas, post-pericardiectomy (Dunning
and others 1998) or surgical resection of the tumour (Aronsohn
1985). Therefore, currently pericardiectomy may be considered
in cases with a heart-base mass on echocardiography.
Subtotal pericardiectomy provided a favourable long-term
prognosis. Despite a perioperative mortality rate of 13 per cent,
the MST of patients now deceased post-pericardiectomy was
1218 days. This was in contrast to a mean survival of 532 days
for echo-negative dogs not undergoing surgery. However, 21
of the 31 dogs undergoing pericardiectomy were still alive at
the time of analysis. Due to prolonged survival, accurate MSTs
cannot be provided at this time.
with pericardiocentesis alone. In addition, other recent studies
indicate prolonged survival in dogs with heart-base masses
post-pericardiectomy (Vicari and others 2001, Ehrhart and
others 2002).
Acknowledgements
The authors would like to thank the referral centres that
contributed cases for this study: Davies-White Veterinary
Specialists, the University of Cambridge, the University of
Edinburgh, the University of Glasgow and Wey Referrals.
Financial assistance was provided by Petsavers.
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22
ORIGINAL WORK
CT-guided fine-needle aspiration
and tissue-core biopsy of lung
lesions in the dog and cat
M. Vignoli(1), G. Gnudi(2), P. Laganga(1), M. Gazzola(3), F. Rossi(1), R. Terragni(1),
M. Di Giancamillo(4), B. Secchiero D(4), S. Citi(5) , A. M. Cantoni(3) , A. Corradi(3)
SUMMARY
Diagnosis of pulmonary lesions on the basis of history and physical examination is often challenging. Diagnostic
imaging is therefore of paramount importance in this field. Radiology has traditionally been considered the elective
diagnostic procedure for these diseases. Nonetheless it is often not possible to differentiate inflammatory/infectious
lesions from neoplastic disease. A correct cyto-histopathological diagnosis is therefore needed for an accurate
diagnosis and subsequent prognostic and therapeutic plan. In human medicine, CT and CT-guided biopsy are
indicated in the presence of lesions which are not adequately diagnosed with other procedures. In the present study
38 dogs and 11 cats, of different sex, breed and size, underwent either CT-guided lung fine-needle aspiration (FNA),
tissue-core biopsy (TCB) or both. Clinical examination, haematology and chest radiography were performed on all
animals. In this study 46 samples out of 56 were diagnostic (82.14%). Ten cases, either due to uncertainty or because
only blood was aspirated, were considered non diagnostic. Sixteen out of 49 cases showed complications (32.6%).
Pneumothorax was seen in 13 cases and mild haemorrhage in three cases. No major complications were encountered.
Key words: Computer Tomography, CT, tissue-core biopsy, fine-needle aspiration, lung lesions, dog, cat.
Introduction
needle aspiration or tissue core biopsy of intrathoracic masses
adjacent to the thoracic wall have been described in human
medicine [6, 7] as well as in veterinary medicine [3]. Furthermore,
the use of the Doppler examination allows the evaluation of the
lesion vascularisation [3]. In human medicine, CT and CT-guided
biopsies are indicated in the presence of lesions which cannot
be adequately diagnosed with other procedures [8-17].
In veterinary medicine, some studies have been published on the
CT-guided biopsy of the brain with stereotactic devices [18-20],
while the description of free hand technique CT-guided biopsy
in animals is still limited [3-5, 21-28] and few details and results
are available regarding sensitivity of the technique. In one
study, the accuracy of the CT-guided biopsy in bone and soft
tissue associated diseases was described; TCB had an accuracy
of 100% both for inflammatory/infectious and neoplastic
Diagnosis of pulmonary lesions on the basis of history and
physical examination is often challenging. Diagnostic imaging is
therefore of paramount importance in this field. Radiology has
traditionally been considered the elective diagnostic procedure
for these diseases. Nonetheless it is often not possible to
differentiate inflammatory/infectious lesions from neoplastic
disease. A correct cyto-histopathological diagnosis is therefore
needed for an accurate diagnosis and subsequent prognostic
and therapeutic plan [1, 5]. Other imaging modalities such as
Fluoroscopy, Ultrasonography (US), Computerized Tomography
(CT) and Magnetic Resonance (MRI) have to be considered as
to the possibilities they offer to the interventional radiologist
in taking take guided biopsy samples [3, 4, 8]. US-guided fine
(1) Veterinary Clinic dell’Orologio – Sasso Marconi (BO), Italy
(2) Section of Radiology and Diagnostic Imaging, Dpt. of Animal Health - University of Parma, Italy
(3) Pathology Unit, Dept. of Animal Health - University of Parma, Italy
(4) Section of Clinical and Experimental Radiology – University of Milan, Italy
(5) Department of Veterinary Clinic – University of Pisa, Italy
Address correspondence and reprint requests to Dr. Massimo Vignoli
Via Gramsci 1/4 –I- 40037 Sasso Marconi (BO) E-mail: [email protected]
23
CT-guided fine-needle aspiration and tissue-core biopsy of lung lesions in the dog and cat - M. Vignoli
1a
1b
1c
Fig. 1 a, b, c Dobermann, male, 7 year old, in right lateral
recumbency. CT of the thorax after contrast medium
administration with a soft tissue window (WW 300, WL 35). The
slice where to biopsy is chosen (a). Then measurements from the
skin to the lesion at different depth are taken (b). Based on this
information, the guide is inserted within the lesion and the position
is checked with further slices from the same area. Streak artifacts
due to the metal are visible (c). Final diagnosis: Adenocarcinoma.
were studied under general anaesthesia and monitored during
the procedure.
The CT examinations were performed to assess the extent of
the lesion, to diagnose eventual metastases, and to take an
aimed biopsy. The pieces of equipment used were a spiral CT
in Sasso Marconi (BO)1) and Milan2), and third generation CT in
Pisa3). The gantry was never tilted and the slice thickness was
3-5 mm depending the size of the lesion. The CT was repeated
after i.v. contrast medium4) administration at the dose of 400800 mg/kg, depending the size of the animal. The CT study
was reviewed with lung (WW 1500, WL – 550) and soft tissue
(WW 300-350, WL 35-40) windows, and then, with the same
soft tissue window, the biopsy was performed. In some cases,
to decrease the streak artefacts, a bone window (WW 20004000, WL 450) was obtained. For FNA a 90 mm long, 21 gauge
(G) spinal needle5) was used. For the TCB, a 14 G guide with
stylet and stopper and a 16 G spring loaded automated needle,
with 23 mm of excursion6) were used. Both the guide and the
automated needle were calibrated at one cm. The technique has
been modified from previously described techniques [23, 26].
All the animals were positioned in a manner offering easiest
access to the lesion based on its location as seen on thoracic
radiographs.
diseases, while with FNA the accuracy was 75%, with an overall
mean accuracy of 94% [25]. In another study, the overall mean
accuracy was 95.7% (100% TCB and 83.3% FNA) [26]. In two
recent reports on the CT-guided biopsy of the intra-thoracic
lesions, an accuracy of 65% for FNA and 83% for TCB [29], and
82% for FNA, was shown [4]. The latter was a preliminary study
on CT-guided FNA and did not take into account TCB.
The purpose of this study is to assess the percentage accuracy
of diagnostic samples and complications of CT-guided FNA and
TCB in the lung lesions of the dog and cat.
Materials and methods
A retrospective study on 49 animals, 38 dogs and 11 cats of
different breed, sex and size, underwent free hand technique
CT-guided biopsy of the lung. Forty-four FNA and 12 TCB
were performed. Only a single specimen was taken from each
lesion, in order to limit the possible complications. Seven dogs
underwent both FNA and TCB. All the cats underwent FNA.
The choice of technique (FNA or TCB) was mainly based on
the size of the lesion. Before the procedure, all the animals
underwent blood and urine examinations. Thoracic radiography
was always performed before CT examination. All the animals
A surgical preparation was done before the CT study. After
the CT study was completed, an assessment of the location
and extent of the lesion and the selection of the target plane
was carried out. The target plane was chosen in an area with
significant changes in order to obtain viable tissue samples.
Areas suspected to be necrotic (with no contrast enhancement)
and large vessels were avoided. Then the CT table was moved
to the target plane, as indicated by the laser light in the gantry.
In this plane, the site for insertion of the needle was subjectively
chosen and marked with a sterile radiopaque metal marker.
Subsequently, additional slices in the area of the marker were
1) GE Pro-Speed Power Spiral CT, Bologna, Italy
2) Philips PQ2000S Spiral CT, Milano, Italy
3) GE CT MAX third generation CT, Pisa, Italy
4) Omnipaque, Amersham Health, Milano, Italy
5) Ago spinale, Artsana. Cuneo, Italy
6) Angelo Franceschini, S.Lazzaro (BO), Italy
24
(Fig. 3 a, b). Benign lesions such as abscesses, cysts or granulomas
were diagnosed in eight cases (six dogs and two cats) (Fig.4 a,
b, c).
Discussion
The CT of the thorax is a very sensitive, but not very specific
method, even with the use of contrast media [4].
In a study on five cats, Henninger (2003) showed that the density
of the lesion measured with Hounsfield Units is not specific for
a neoplastic disease versus an inflammatory disease and that
contrast medium does not give differential enhancement [27].
Therefore a biopsy is needed to establish a final diagnosis.
In this study, the percutaneous CT-guided biopsy was used to
obtain a diagnostic sample in 46 out of 56 biopsy samples,
with an overall mean accuracy of 82.1%. Tidwell and Johnson
(1994), reported four lung and one cranial mediastinal biopsies.
All the samples, four evaluated for cytology and three for
histopathology, were diagnostic [22]. One study has reported
an accuracy of 65% for FNA and 83% for TCB [29]. In human
medicine, the diagnostic accuracy of the core biopsy under CT
guidance is reported as high, between 88% [16] and 95% [17],
with similar results for FNA, 85% [14]. It has been reported in the
literature that carcinomas exfoliate better than sarcomas [2, 3],
and since most of the malignancies in the lung are carcinomas,
this may explain why there is a high accuracy with CT-guided
FNA.
The localization of the needle tip in the percutaneous CT-guided
biopsy has been considered the key point for the success of
the procedure. It is of paramount importance to differentiate
between the true tip of the needle from the impression of a
false tip, which is visible when the CT scan comprises only the
angled needle [5]. It has been reported that the “low density”
artifact visibile immediately adjacent to the distal part of the tip
of the needle may create a false positive impression; therefore
the correct position of the needle must be determined by
evaluating the shape and the distinct nature of the tip rather
than the “low density” artifact [21].
The choice of biopsy needle and the position of the animal
depends on the localisation, dimension and distance from the
Fig.2. Same dog as in Fig. 1. Lung window: a mild to moderate
pneumothorax was present in the post biopsy image (d).
acquired to measure the distance from the skin to the proximal
and distal borders of the lesion and to the area to biopsy. Those
measurements facilitated the choice of correct depth and angle
of insertion of the needle.
The CT table was moved out of the gantry so that the spinal
needle (for FNA) or the metallic guide (for TCB) could be placed
and advanced to the preset distance and angle following a
skin incision. The position of the spinal needle/guide tip was
evaluated with additional images and the needle placement was
corrected when necessary before the lesion was sampled. For
FNA, once the needle was in a correct position, the stylet was
retracted and suction with a syringe was applied. For TCB, when
the metallic guide was considered to be in a correct position, the
stylet was retracted and the automated needle inserted within
the guide to the lesion and a tissue-core biopsy was obtained
(Fig. 1a, b, c). Further images were taken in the area of the lesion
in order to check for complications. All the animals were clinically
monitored after the procedure for two to 24 hours depending
on clinical signs and the severity of any complications.
Results
The tip of the needle was visualized within the lesion in all the
patients. The diagnosis was reached in 46 out of 56 samples
(Tab. 1). Thirty five of 44 FNA (79.5%) and 11 of 12 TCB (91.7%)
were diagnostic. Nine of 44 FNA were considered not diagnostic
because only blood was aspirated. One TCB was not diagnostic
because only fibrous tissue was recovered. In the same dog, the
FNA was diagnostic for carcinoma. The overall mean accuracy
was 82.1%. Sixteen out of 49 cases showed complications
(32.6%). Mild to moderate pneumothorax was present in
12 cases, and one severe pneumothorax was present after a
TCB, however this did not require any surgical intervention.
Pneumothorax was present after five FNA (11.4 %) and eight
TCB (66.7%) (Fig.2). The deeper the lesion, the more severe
the pneumothorax, with a range of two to seven centimetres.
However, in some deep lesions, no pneumothorax was visible.
In three cases, a mild haemorrhage was present in deep lesions,
with collapse of the dependent lung.
Neoplastic lesions were detected in 31 cases (25 dogs and six
cats). Thirty were carcinomas and one malignant histiocytosis
Fig. 3 a, b. Crossbreed, female, 12 year old. CT of thorax in sternal
recumbency and with a soft tissue window (WW 300, WL 40).
After contrast medium administration a large mass in the left
caudal lung lobe is shown with a non-homogenous enhancement
(a). Biopsy phase. The guide is inserted within the lesion. Streak
artifact are visibile (b). Final diagnosis: Adenocarcinoma.
25
Table 1: CT-procedure and results of 38 dogs and 11 cats with toracic lesions.
Cases
number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
Signalement: breed, age in years (y),
sex (M: male; F: female)
Miniature Poodle, 10 y, F
Miniature Poodle, 11 y, F
Bouvier de Flandres, 7 y, F
Boxer, 11 y, M
Brittany Spaniel, 9 y, F
Griffon Kort., 10 y, M
Mix, 10 y, F
Mix, 10 y, M
Mix, 11 y, F
Mix, 14 y, F
Bernese Mountain, 8 y, M
German Shepherd, 10 y, F
German Shepherd, 11 y, M
Pekingese, 11y, F
Pointer, 13 y, F
Rottweiler, 9 y, M
Siberian Husky, 12 y, F
Schnauzer, 9 y, F
English Setter, 8 y, F
German Shepherd, 7 y, M
Mix, 9 y, M
Mix, 12 y, M
Mix, 7 y, F
Mix, 10 y, M
German Shepherd dog, 11 y, M
Mix, 9 y, F
Mix, 14 y, M
Labrador Retriever, 17 y, M
Mix, 4 y, F
Boxer 9 y, M
Boxer, 8 y, M
Weimaraner, M 18 m
Mix, 12 y, F
Location of the lesion
in the lung lobe
Right middle
Right caudal
Left caudal
Left caudal
Right cranial
Right caudal
Left caudal
Right middle
Right caudal
Left caudal
Right middle
Left caudal
Left caudal
Left caudal
Left caudal
Right caudal
Right cranial
Right middle
Right caudal
Right cranial
Right cranial
Right caudal
Left cranial
Right middle
Right middle
Left cranial
Left caudal
Right caudal
Right accessory
Right middle
Left caudal
Left caudal
Left caudal
Left caudal
35
Dobermann, 12 y, M
Right caudal
36
Airdale terrier, 12 y, M
Right caudal
37
Labrador Retriever, 9 y, F
Left caudal
38
Right middle
39
European Shorthair cat, 13 y, F
Left caudal
40
European Shorthair cat, 8 y, M
Left cranial
41
Left cranial
42
Persian cat, 13 y, M
Right caudal
43
Persian cat, 9 y, F
Right caudal
44
Siamese cat, 15 y, M
Left caudal
45
Persian cat, 13 y
Right caudal
46
European Shorthair cat, 14 y, F
Left cranial
47
Right caudal
48
Right caudal
49
Left caudal
TCB = Tissue-core biopsy; FNA = Fine-needle aspiration.
26
Biopsy
technique*
FNA
FNA
FNA
TCB
FNA
FNA
FNA
FNA
FNA
TCB
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
TCB
FNA
FNA
FNA
FNA
FNA +TCB
FNA
FNA + TCB
FNA + TCB
FNA
FNA
FNA + TCB
FNA + TCB
FNA + TCB
TCB
FNA +TCB
TCB
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
FNA
Histological/Cytological
diagnosis
Carcinoma
Non-diagnostic
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Non-diagnostic
Carcinoma
Carcinoma
Malignant histiocytosis
Carcinoma
Carcinoma
Carcinoma
Non-diagnostica
Abscess
Granuloma
Non-diagnostic
Abscess
Carcinoma
Non-diagnostic
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Abscess
Carcinoma
Abscess
Non-diagnostic
Abscess
Carcinoma
FNA: Carcinoma
TCB: Non-diagnostic
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Carcinoma
Cyst
Non-diagnostic
Carcinoma
Non-diagnostic
Carcinoma
Carcinoma
Carcinoma
Abscess
Non-diagnostic
Carcinoma
Fig. 4 a, b, c. Domestic short hair cat, female, 15 year old. CT of the thorax in sternal recumbency and with a lung window (WW 1500,
WL – 550). A small nodule, about 1 cm in diameter is visible in the right caudal lung lobe (a). Measurements (b) and phase of the biopsy
(c) are visible. Final diagnosis: Granuloma.
skin surface of the lesion [3]. In the present study, 21-G spinal
needle was used for FNA. A fine needle has been recommended
in order to avoid aspiration of blood [3]. For TCB, a 14-G
calibrated guide with stylet was employed, which functioned as
a support for the 16-G calibrated automated needle. Indeed, the
length of the automated needle and the weight of the handle
of the needle did not allow direct biopsy. The use of different
techniques (FNA or TCB) was chosen mainly based on the size of
the lesion, considering the 23 mm of extension of the automatic
needle. Because of this, we did not consider it possible to take a
TCB in lesions smaller than 4 cm.
We observed some complications including three mild
haemorrhages and 12 cases of mild to moderate pneumothorax.
Only one severe pneumothorax was seen after a TCB and none
of them required surgical intervention. Most of the complication
were seen after TCB, probably due to the larger size of the
guide compared to that of the needle used for FNA and the
depth of the biopsy lesions. However, with some deep lesions
neither haemorrhage nor pneumothorax was observed. Those
complications were not related to the size of the lesion. In one
study it was reported that the deeper the lesion, the more severe
the pneumothorax was likely to be, but no clinical manifestations
were noted in that study [29]. Since passage through more lung
tissue accurs to get into a deeper lesion, we can speculate that
this could be the reason for the higher number of pneumothorax
complications seen with deep lesions. However we still cannot
explain why the biopsy in some deep lesion did not create
any pneumothorax. In one case, dog n° 34, Tab. 1, the severe
pneumothorax created was probably the cause of not being able
to obtain a diagnostic sample. In the same case the FNA was
diagnostic for carcinoma. In human medicine, pneumothorax
is the most common complication of percutaneous CT-guided
lung biopsy and ranges from 8 to 61% [30, 31]. In one study on
289 patients, it was reported that application of a thoracic drain
was necessary in 14% of the cases. In the same study it was
reported that deeper lesions, which require a wider trajectory
angle, were risk factors for pneumothorax [30]. In another study
it was reported that the transthoracic needle biopsy can be
performed with high-diagnostic yield in patients with iatrogenic
stable pneumothorax caused by other procedures, such as CT-
guided biopsy, US-guided biopsy or transbronchial lung biopsy
[32].
The respiratory movements did not cause problems during
the procedure. However, it is important not to move the
animal during the procedure to avoid loosing the target which
necessitates restarting the examination.
In this study the animals were positioned in different modes
of recumbence with the goal being to reach the lesion more
easily on basis of lesion localization obtained by radiography.
However, it is our opinion that lateral recumbency should be
avoided, if possible, because metastases may be missed due
to partial collapse of the dependent lung. Another option is to
position the animal in ventrodorsal or dorsoventral recumbency
in order to examine for metastases, and then reposition the
animal in lateral recumbency to obtain the biopsy. The latter
method however, which includes a retake of the scout views
and scanning against the mass involves a longer examination
time and an additional injection of contrast medium.
The i.v. administration of non-ionic iodinated contrast medium,
can give useful information. Indeed, the enhancement of the
lesion allows the operator to biopsy viable tissue and to avoid
large vessels [4, 22, 26].
CT allows better evaluation of the extent of the lesion than US
or fluoroscopy [4, 26], particularly in lesions surrounded by gas,
as opposed to in US [3, 26]. The CT is a more sensitive technique
to examine for metastases when compared to fluoroscopy and
conventional radiology [4].
Some disadvantages of CT compared to other techniques are
reported, however [3, 26].
The time for the whole procedure is variable depending on the
size, location of the lesion, experience of the radiologist and
CT machine available. With a spiral CT the whole procedure
(scanning and biopsy) takes from 5 to 30 minutes.
In conclusion, CT-guided biopsy is a safe and accurate technique.
The only limitation we observed is when a lesion smaller than
4 cm is biopsied with the automated needle. CT is useful for
examination of areas that are difficult to reach with other
techniques, especially in lesions surrounded by gas. Moreover,
within the same examination, it is possible to assess the possible
presence of metastases.
27
Acknowledgements
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[18] KOBLIK (P.D.), LECOTEUR (R.A.), HIGGINS (R.J.), FICK (J.), KORTZ
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[23] TIDWELL (A.S.), JOHNSON (K.L.) - Indication and Technique for
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[24] TIDWELL (A.S.), JOHNSON (K.L.) - Application of CT guided
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[25] VIGNOLI (M.), ROSSI (F.), POZZI (L.), OHLERTH (S.), CORLAZZOLI
(D.), TERRAGNI (R.), SARLI (G.) - CT-guided biopsy in the axial
and appendicular skeleton. EAVDI/ECVDI Annual Meeting, 2002
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[26] VIGNOLI (M.), OHLERTH (S.), ROSSI (F.), POZZI (L.), TERRAGNI (R.),
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[27] HENNINGER (W.) - Use of computed tomography in the diseased
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[28] DI GIANCAMILLO (M.), SECCHINO (B.), STEFANELLO (D.),
CANIATTI (M.) - Impiego della biopsia con ago sottile TC-guidata
nella pratica clinica veterinaria: proposta di un protocollo di
esecuzione. Atti X° Congresso SICV, Bologna, 19-21 Giugno,
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[29] ZEKAS (L.J.), CRAWFORD (J.T.) - Computer Tomography-guided
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The authors would like to acknowledge the contribution
of SPINNER Consortium of the University of Bologna
(European Union, Emilia-Romagna Region, Ministry of the Work
and Social Politics)
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28
REPRINT PAPER (SVK)
Clinical efficacy of Pimobendan
versus Benazepril for the treatment
of acquired atrioventricular valvular
disease in dogs
C. W. Lombard(1), Claudio M. Bussadori (2), O. Jöns (3)
SUMMARY
Seventy-six dogs with clinical acquired atrioventricular valvular disease were evaluated to determine the efficacy
of pimobendan (n=41) versus benazepril hydrochloride (n=35) in a randomised, positive-controlled, multicentre
study. The study was divided into 56-day and long-term evaluation periods. In a subgroup of dogs with concurrent
frusemide treatment (pimobendan [n=31], benazepril [n=25]), the Heart Insufficiency Score improved in favour
of pimobendan (P=0.0011), equating to a superior overall efficacy rating (P<0.0001) at day 56. Long-term median
survival (i.e., death or treatment failure) for dogs receiving pimobendan was 415 days versus 128 days for dogs not on
pimobendan (P=0.0022).
treated dogs, long-term prognosis is predicated on response to
treatment, the occurrence of cardiac complications (e.g., cardiac
arrhythmias, cardiac tamponade secondary to atrial rupture,
fulminant pulmonary oedema from chordae tendineae rupture),
and the occurrence of other illnesses (e.g., concurrent respiratory
disease, renal failure, hyperadrenocorticism, etc.).
Data to date have defined a role for the use of diuretics (e.g.,
frusemide), hydralazine, and angiotensin-converting enzyme
(ACE) inhibitors in symptomatic, but not asymptomatic (i.e.,
occult or preclinical) canine atrioventricular valvular disease
[5-10]. Use of such agents results in improvements in both
quality and quantity of life through reductions in preload,
afterload, and cardiac workload; however, recent data derived
from experimental canine heart failure models of atrioventricular
valvular insufficiency have failed to identify improvements in
cardiac remodeling with ACE-inhibitor use and have raised
concern that ACE-inhibitors may limit long-term survival because
of their negative impact on myocardial protein metabolism
and myocardial function. [11,12] Additionally, new data have
countered the long-held belief that myocardial systolic function
This paper originally appeared in: J Am Anim Hosp Assoc*
(2006) ,42 p249-261
Introduction
Atrioventricular (myxomatous) valvular disease is the most
common acquired canine cardiac disease, with mitral valvular
insufficiency predominating. [1-3] Atrioventricular valvular
disease is slowly progressive, resulting in a prolonged
asymptomatic or preclinical phase (International Small Animal
Cardiac Health Council [ISACHC] Class Ia and Ib); however,
once valvular disease progresses to overt clinical signs of heart
failure (ISACHC ≥ II), therapeutic intervention is indicated.
Therapeutic goals for treating heart failure from atrioventricular
valvular disease are to mitigate the consequences of volume
overload (preload and afterload reduction), to reduce cardiac
workload, and to retard volume overload-mediated cardiac
remodelling which, while beneficial in the short term, has
negative implications for long-term cardiac function. [4] For
(1) Klinik für kleine Haustiere, Universität Bern ,Länggassstrasse 128, CH- 3012, Bern.
(2)Clinica Gran Sasso, Via Donatello 26,I- 20131 Milano.
(3) Boehringer Ingelheim Vetmedica GmbH, Preclinical and Clinical Development,D -55216 Ingelheim/Rhein.
All correspondence to Dr. Jöns. E-mail : [email protected]
This study was sponsored and funded by Boehringer Ingelheim Vetmedica GmbH,Ingelheim/Rhein, Germany.
Animals were enrolled in the Veterinary Study for the Confirmation of Pimobendan in Canine Endocardiosis (VetSCOPE).
*Presented by SVK /ASMPA (Switzerland)
FECAVA are grateful to the JAAHA for permission to reprint this paper from the above mentioned Journal
29
Clinical efficacy of Pimobendan versus Benazepril - C. W. Lombard
remains adequate until advanced or late-stage atrioventricular
valvular disease, based on the findings of reduced pulmonary
transit times that indicate reduced systolic/ myocardial function
even in early disease states [13]. As a result, various other
pharmaceuticals are being investigated in an effort to improve
both the quality of life and long-term prognosis of dogs with
heart failure from atrioventricular valvular disease.
Pimobendan is a novel cardiac pharmaceutical, termed an
“inodilator” because it possesses both positive inotropic and
balanced peripheral vasodilatation properties [14]. Unlike
historical positive inotropes (e.g. digoxin, milrinone) which
function by increasing intracellular calcium concentrations,
resulting in increased cardiac energy and oxygen requirements,
pimobendan acts as a positive inotrope principally by enhancing
the affinity of myocardial troponin C to existing intracellular
calcium [15,16]. The result is improved contractility without
additional increased myocardial oxygen or energy requirements
[17]. Peripherally, pimobendan is a phosphodiesterase III (PDE
III) inhibitor, resulting in balanced peripheral vasodilatation
through increased efflux of intracellular calcium from vascular
smooth muscle [14,18-20]. Additional properties include
reversal of desensitisation of baroreceptors, improved cardiac
relaxation (lusitropy), reduced platelet aggregation, and an
anti-inflammatory effect mediated through favourable cytokine
modulation [21-24].
Based on pimobendan’s pharmacodynamic profile, it appears to
be ideally suited to the treatment of heart failure associated with
atrioventricular valvular disease. Studies in Doberman pinschers
with dilated cardiomyopathy (DCM) and in humans with heart
failure have demonstrated improvement in quality and quantity
of life when pimobendan was added to traditional (i.e., diuretic,
ACE-inhibitor, and digoxin) therapy [25-27]. Preliminary data
from dogs with overt, clinical heart failure from atrioventricular
valvular disease support an early therapeutic role and an
advantage of pimobendan over (or in addition to) ACE-inhibitor
therapy [28-31].
The primary goal of this study was to evaluate the efficacy
of pimobendan, in comparison to benazepril hydrochloride,
in improving the quality and quantity of life in dogs suffering
from overt, clinical heart failure from atrioventricular valvular
disease. In addition to evaluating efficacy, data were collected
to evaluate product safety and any impact on radiographic and
echocardiographic indices.
hospitalisation required) from acquired mitral and/or tricuspid
valvular disease. [32] All dogs had symptomatic heart failure as
indicated by signalment, history, general physical examination,
plain radiography, and echocardiography. In addition to an
ISACHC Class II or greater designation, enrolled dogs also had
evidence of reduced cardiac function as demonstrated by one
or more of the following abnormalities: pulmonary oedema and
increased vertebral heart score (>10.5) on thoracic radiography,
and ventricular dilatation, left atrial dilatation, and normal to
reduced fractional shortening (FS) on echocardiography [33].
Exclusion criteria included concomitant congenital heart
disease, hypertrophic or DCM, ISACHC Class I heart failure
(i.e., asymptomatic; Ia, no signs of compensation; Ib, signs
of compensation [e.g., cardiac enlargement]), renal disease
(serum creatinine concentration >2.5 mg/dL [220 μmol/L]),
severe endocrine diseases (e.g., diabetes mellitus or insipidus,
hyperadrenocorticism), pregnancy, and body weight >40 kg. The
last criterion was used because primary atrioventricular valvular
disease is unlikely in dogs >40 kg, and the weight restriction
allowed for a more homogeneous study population.
The study was conducted as a blinded, randomised, positivecontrolled (i.e., benazepril hydrochloride), multicentre study. The
study had a mandatory 56-day treatment period (as dictated
by the French regulatory authorities) that was followed by an
optional long-term treatment period and was conducted in
accordance with guidelines for Good Clinical Practice. a
The 56-Day Treatment Period
In the 56-day treatment period, dogs were allocated at random
to receive either pimobendan b (0.2 to 0.3 mg/kg per os [PO] q
12 hours) or benazepril hydrochloride c (0.25 to 0.5 mg/kg PO q
24 hours). In order to allow complete blinding of the study, all
dogs received two treatments: either pimobendan with placebo
(pimobendan group) or benazepril hydrochloride with placebo
(benazepril hydrochloride group).
The dogs were examined on days 0 (prior to first treatment),
7, and 56. The primary variable investigated at each followup examination was the Heart Insufficiency Score derived
from the ISACHC classification of the stage of atrioventricular
valvular disease. The ISACHC classification was based on a
combination of history, physical examination, and the results of
diagnostic tests as listed below. Secondary variables recorded
were exercise tolerance, demeanor, appetite, respiratory
effort, cough frequency, and nocturnal dyspnoea. Data from
electrocardiography (ECG), thoracic radiography (i.e., presence
of pulmonary oedema, vertebral heart score), and M-mode
echocardiography (i.e., FS, left atrial to aortic root ratio [La:
Ao], end-systolic volume index [ESVI; left ventricular internal
dimension at systole normalised to body surface area], and enddiastolic volume index [EDVI; left ventricular internal dimension
at diastole normalised to body surface area]) were collected on
all dogs prior to initiation of the study. A serum biochemical
profile and ECG were required as part of the initial evaluation in
order to ensure that all inclusion/exclusion criteria were met, but
it was left to the discretion of the individual investigator as to
whether these tests were repeated at subsequent examinations.
Echocardiography was repeated at days 7 and 56, and thoracic
radiography was repeated at day 56. At the end of the 56day treatment period, an overall clinical efficacy assessment
Materials And Methods
Study Animals and Design
Seventy-six privately owned dogs with spontaneous
atrioventricular valvular disease that were presented to one of
11 different veterinary centres in Europe, (Belgium [n=2], France
[n=4], Germany [n=1], Italy [n=2], and Switzerland [n=2])
were enrolled in the Veterinary Study for the Confirmation of
Pimobendan in Canine Endocardiosis (VetSCOPE) between
November 23, 2001 and July 16, 2003. Enrollment was
restricted to dogs that were diagnosed with ISACHC Class
II (i.e., mild to moderate heart failure; clinical signs of heart
failure that are evident at rest or with mild exercise, which
adversely affect quality of life) or ISACHC Class III heart failure
(i.e., advanced heart failure; IIIa, outpatient care possible; IIIb,
30
Table 1 Scoring Protocol for Secondary Variables During the 56-Day Study Period
Variable
Score
Clinical Correlate
Exercise tolerance
1 (Very good)
Dog moved around with ease, was able to fully exercise
2 (Good)
Dog moved around with ease, was not able to fully exercise; ability to run was reduced
3 (Moderate)
Dog was less active than normal, moved around a few times per day, avoided long walks
4 (Poor)
Dog was inactive and would get up only to eat, drink, or urinate
1
Alert, responsive
2
Mildly depressed
3
Moderately depressed
4
Minimally responsive
5
Unresponsive
1
Increased
2
Normal
3
Decreased (2/3 normal)
Demeanor
Appetite
Respiratory effort
Coughing
4
Markedly decreased (<2/3 normal)
1
Normal
2
Mildly increased effort
3
Laboured
4
Respiratory distress
1
None
2
Occasional
3
Frequent
4
Persistent
Nocturnal dyspnoea 1
None
2
Dog coughed from time to time during the night, but no other clinical signs of dyspnoea
or restlessness were present
3
Dog coughed consistently; increased respiratory effort or restlessness during the night
was made for each dog. Variable assessment in each dog was
consistently done by the same investigator.
Grading of the primary variable Heart Insufficiency Score was
based on assigning a score of 1 for ISACHC Class Ia; 2 for Class
Ib; 3 for Class II; 4 for Class IIIa; and 5 for Class IIIb. Grading
of secondary variables was done based on owner assessments
using a numerical scale [Table 1]. Vertebral heart scoring used a
published methodology, with a reference range of 8.5 to 10.5
[33]. Pulmonary oedema was graded as 1 for no pulmonary
oedema; 2 for mild interstitial density; 3 for moderate interstitial
density; 4 for the presence of an alveolar pattern; and 5 for
severe consolidation. Electrocardiography was performed with
the dogs in right lateral recumbency, and a standard six-lead
ECG tracing was obtained for analysis.
At the 56-day examination, the subjective overall clinical efficacy
was scored using the following scoring system: 1 = very good,
clinical signs greatly improved with treatment; 2 = good, clinical
signs improved with treatment; 3 = partial response, clinical
signs slightly improved with treatment; 4 = insufficient response,
clinical signs remained the same; and 5 = therapy failure, clinical
signs worsened. For cases that did not complete the 56-day
period because of a cardiac- specific reason, the overall clinical
efficacy was calculated as a therapy failure for the final visit.
Individual dog scores for each primary, secondary, and overall
efficacy variable at each evaluation were used to derive a group
mean ± standard deviation (SD) for that variable/time point
and were used to determine any statistically significant group
differences.
At the end of the study, the survival status of each dog was
evaluated. For dogs confirmed to be alive at the date of the final
study visit, this date was taken as the survival date. For dogs
not confirmed by the investigators to still be alive, the date of
the last examination of the dog during the optional period was
taken as the survival date. Cases still alive were censored by the
statistician.
Concomitant Treatment
During the 56-day treatment period, frusemide was allowed,
with the dosage left to the discretion of the investigator. An
antiarrhythmic agent was also allowed in dogs with severe
arrhythmias. Treatments for other concurrent diseases (e.g.,
respiratory tract infection) were allowed and entered as part
of the study data. The use of other ACE-inhibitors, digoxin, or
other positive inotropic drugs was not permitted.
31
Long-Term Optional Treatment Period
At the end of the 56-day treatment period, owners of surviving
dogs were given the option of entering their dogs into a longterm treatment trial. For dogs that entered the optional longterm study period, the treatment code (i.e. blinding) was broken.
Any required treatments could be added; however, dogs in the
benazepril hydrochloride group received pimobendan only if
treatment failure made such a combination necessary.
For estimating long-term survival, death and treatment failure
were considered the end points. For the benazepril hydrochloride
group, treatment failure was defined as progressive clinical signs
(as defined by the secondary variables) refractory to treatment
that necessitated the addition of pimobendan or removal from
the study. For the pimobendan group, treatment failure was
defined as progressive clinical signs (as defined by the secondary
variables) refractory to all treatment. Comparisons were made
between pimobendan- treated and non-pimobendan-treated
groups on a background of traditional therapies (i.e., ± frusemide
and ± benazepril) as deemed necessary by the attending clinician.
Dogs removed from the study because of treatment failure were
evaluated statistically as non-survivors, and the day of removal
was used to calculate survival time.
During the two phases of the study, adverse drug reactions were
recorded, and the death of any dog was followed by a complete
post-mortem examination.
respect to the secondary variables were designed as two-sided
tests. AP value of <0.05 was considered statistically significant.
Survival curves were estimated according to Kaplan-Meier.
Cases were censored if animals were still alive at the day 56
visit or if death or withdrawal did not occur from heart failure.
The logrank test was performed for the comparison of the two
treatment groups. The statistical analysis was performed using
statistical software programs. d,e
Results
Study Animals
Overall, 76 dogs (pimobendan treatment group [n=41],
benazepril hydrochloride treatment group [n=35]) representing
31 different breeds were enrolled in the study. All dogs had
clinical signs of heart failure secondary to atrioventricular
valvular disease. Mean (± SD) duration of signs was 4.05±8.37
months for the pimobendan group and 2.77±4.62 months for
the benazepril group. No clinically relevant differences were
noted between the groups prior to the initiation of therapy.
In the initial serum biochemical profiles, a mild but statistically
significant (P=0.0175) difference in serum chloride was found
between the pimobendan (114.0±7.19 mmol/L; reference
range 102.0 to 118.0 mmol/L) and benazepril hydrochloride
(108.7±8.91 mmol/L) groups; however, all values were in the
normal reference range and not considered to be clinically
significant. Follow-up evaluations did not always occur on day 7
or 56, but ranged from day 6 to 8 and day 51 to 62, respectively.
Electrocardiography Arrhythmias were demonstrated on the
pretreatment ECGs in 11/41 (27%) dogs in the pimobendan
group and in 10/35 (29%) dogs in the benazepril hydrochloride
group. Sinus tachycardia (pimobendan [n=3], benazepril [n=5])
and atrial premature complexes (pimobendan [n=5], benazepril
[n=5]) predominated, and ventricular premature complexes
(VPCs) were found in three dogs in the pimobendan group and
in one dog in the benazepril group. One dog in the benazepril
group had both VPCs and atrial premature complexes. Only
one of the arrhythmias required treatment beginning at day 0
(i.e. atrial fibrillation was treated with diltiazem in a dog from
the benazepril group). This dog was subsequently classified
as a treatment failure during the 56- day portion of the study.
Follow-up ECGs were not performed on any other dogs.
Statistical Analysis
The entire dataset derived from the 76 dogs enrolled in the study
was evaluated for the primary variable of the Heart Insufficiency
Score, the secondary variable of overall efficacy, and the survival
times during both the 56-day and optional long-term portions
of the study. To eliminate the confounding influence of the
frusemide therapy, statistical analysis was performed separately
on the dataset derived from the subpopulation of 56 dogs
that were also treated with frusemide. This subpopulation was
evaluated for the primary variable of the Heart Insufficiency
Score; the secondary variables of demeanor, exercise tolerance,
respiratory effort, appetite, cough, nocturnal dyspnoea, and
overall efficacy; as well as for survival during both the 56-day
and optional long-term portions of the study.
The pimobendan group was said to be non-inferior if the
lower bound of the one-sided 95% confidence interval for the
Mann-Whitney statistic was higher than the threshold value
corresponding to the lower limit of the equivalence range of
0.3. Corresponding threshold values were calculated using
the normal distribution. In cases of proven non-inferiority, the
pimobendan group was tested for superiority to the benazepril
group by the Wilcoxon’s Mann-Whitney test. With respect to
the secondary variables, the groups were compared using the
two-sided t-test for normally distributed data, and in other
cases, the two-sided Wilcoxon’s Mann- Whitney test or Fisher’s
exact test was used.
For all parameters, original data as well as changes from baseline
(day 0) were evaluated. Repeated measures analysis of variables
with more than one treatment time was substituted by the
worst case (maximum score) for scored variables and by the last
measured value for other variables. Repeated measures analysis
was confined to the subpopulation of 56 dogs on concurrent
frusemide therapy. All tests on differences between groups with
The 56-Day Study Period
The primary variable, the Heart Insufficiency Score based on
ISACHC heart failure classification, improved in 31/37 (84%)
dogs treated with pimobendan compared with 15/27 (56%)
dogs treated with benazepril (P=0.023; Fisher’s exact test).
At the day 56 evaluation, ISACHC classification Ib (score = 2;
i.e. no clinical signs) was recorded for 28/37 (76%) dogs on
pimobendan versus 13/27 (48%) dogs treated with benazepril.
Differences between the groups were statistically significant in
favour of pimobendan on both day 7 (P=0.0280) and day 56
(P=0.0201). At day 56, overall efficacy was rated as very good
or good in 33/39 (85%) dogs on pimobendan versus 14/34
(41%) dogs treated with benazepril (P<0.0001).
Of the 41 dogs in the pimobendan group, four were removed
from the study during the 56-day period. Two dogs were
removed because of non-compliance by the owner; one was
32
Table 2. Initial Clinical Data on 56 Dogs Treated Concurrently With Frusemide
Variable
Pimobendan
Benazepril
Total
Total no. dogs
31
25
56
Number of breeds*
17
17
31
Mean age (y ± SD†)
10.8±1.99
11.68±3.01
11.2±2.51
Mean body weight (kg ± SD)
9.95±6.26
12.14±8.36
10.93±7.28
Sex
Male
18
13
31
Castrated male
4
3
7
Female
5
3
8
Spayed female
4
6
10
Duration of cardiac signs prior to study (mos ± SD)
2.83±4.70
2.86±5.36
2.84±4.95
19 (61%)
12 (48%)
31 (55%)
Diagnosis of valvular insufficiency (no. and percentage of dogs)
Mitral
Tricuspid
0 (0%)
0 (0%)
0 (0%)
12 (39%)
13 (52%)
25 (45%)
23 (74%)
16 (64%)
39 (70%)
ISACHC IIIa
7 (23%)
8 (32%)
15 (27%)
ISACHC IIIb
1 (3%)
1 (4%)
2 (4%)
Vertebral heart score (mean ± SD)
12.1±1.2
12.0±1.1
12.1±1.2
Mean frusemide dosage (mean ± SD mg/kg per d)
2.92±1.24
3.32±1.14
3.10±1.20
Mitral and tricuspid
Class of heart failure‡
ISACHC II
* Different types of mixed-breed dogs were counted as one breed.
† SD=standard deviation
‡ ISACHC=International Small Animal Cardiac Health Council Score; see text for class definitions
the pimobendan group and 27 dogs from the benazepril group.
At the time of conclusion of the study, 25 dogs remained from
the pimobendan group and 13 remained from the benazepril
group. Necropsies were performed in two dogs that were
euthanased. One dog on benazepril therapy had a hepatic
carcinoma. One dog on pimobendan had pulmonary oedema
and pneumonia associated with congestive heart failure. Median
survival time for dogs treated with pimobendan was 430 days
versus 228 days for dogs that received no pimobendan, with
Kaplan-Meier analysis revealing significant differences in favour
of pimobendan (P=0.0020).
removed because of cardiac-related euthanasia; and one was
removed due to sudden death assessed as cardiac related. In
the benazepril group, eight dogs were removed from the study
during the 56-day period. Three dogs died suddenly (assessed
as cardiac related); two were euthanased (one for a cardiac
reason and one because of seizures); and three were assessed as
treatment failures from deterioration of cardiac signs. Therefore,
two dogs in the pimobendan group and seven in the benazepril
group were defined as dead or euthanased from cardiac disease.
Survival analysis according to Kaplan-Meier calculations revealed
a significant difference in favor of pimobendan (P=0.0386).
Four dogs experienced adverse events related to drug
administration—not from cardiac disease—during the 56- day
study period. Three adverse events occurred in pimobendantreated animals, and one occurred in the benazepril group.
Diarrhoea (n=1), soft stool (n=1), and vomiting (n=1) occurred in
dogs from the pimobendan group, and colitis (n=1) occurred in a
benazepril-treated dog. Of the three pimobendan-treated dogs
reported with gastrointestinal signs, one dog also experienced
tachypnoea, weakness, and excitation; another dog developed
restlessness. No necropsies were performed during the 56-day
study period.
Concomitant Therapy
Thirty-one pimobendan-treated dogs and 25 benazepril treated
dogs were on frusemide treatment at the time of enrollment in
the study. All dogs not on frusemide at day 0 completed the 56day study period without requiring the addition of frusemide.
Additional therapeutics used to address the progression of
heart failure during the long-term portion of this study included
aminophylline (n=3); dextromethorphan- containing cough
syrup (n=2) or terbutaline (n=3) for intractable coughing;
hydralazine (n=1) or amlodipine (n=1) for additional afterload
reduction; spironolactone (n=6) for additional diuretic support;
digoxin (n=2) for acute pulmonary oedema or atrial fibrillation;
and carvedilol (n=1) for lack of improvement of cardiac signs.
Optional Long-Term Study Period
All dogs alive at the end of the 56-day study period were entered
into the optional long-term study, which included 37 dogs from
33
Figure 1—Box and whiskers plot
illustrating the overall clinical
efficacy assessment on day 56 in
the subpopulation of 56 dogs on
concurrent frusemide therapy. Boxplots include the median values, and
the 10/90 percentiles are presented
as whiskers. The points are single
outliers. Efficacy was rated as
very good or good in 86% of the
pimobendan-treated cases versus
25% of the benazepril-treated cases
(P<0.0001). On the Y-axis, the
numbers in parentheses represent
efficacy scores. These results indicate
a statistical difference (P<0.0001)
based on Wilcoxon’s Mann-Whitney
test.
Figure 2—Kaplan-Meier estimate
demonstrating the percentage of dogs
from the subpopulation of 56 dogs on
concurrent frusemide therapy that
survived over time during the 56-day
treatment period. The pimobendan
treatment group had a significantly
greater (P=0.0246) percentage
of survival than the benazepril
treatment group. Dogs were censored
if they were still alive or if withdrawal
from the study was not related to
heart failure.
Concurrent Frusemide Therapy
The subpopulation of dogs on concurrent frusemide therapy
included 56 dogs (31 in the pimobendan group and 25 in the
benazepril group) [Table 2]. All dogs had overt signs of heart
failure secondary to atrioventricular valvular disease (July/August
2006, Vol. 42 Pimobendan 253). Mean durations of signs prior
to study enrollment were 2.83±4.7 months for the pimobendan
group and 2.86±5.36 months for the benazepril group. No
statistically significant differences were found between the
groups prior to the initiation of therapy for any parameter (i.e.,
age, sex, weight, duration of clinical signs, or Heart Insufficiency
Score) other than serum chloride (pimobendan group, mean
113.4±6.93 mmol/L; benazepril group, mean 107.0±9.60
mmol/L; P=0.0084). These findings were similar to those of the
entire 56-day group and were considered clinically irrelevant.
The overall dose of frusemide decreased from day 0 (mean
2.92±1.24 mg/kg per day; n=31) to day 56 (mean 2.70±0.95
mg/kg per day; n=27) in the pimobendan group, with a mean
change from baseline of -0.32±0.85 mg/kg per day. The overall
dose of frusemide increased from day 0 (mean 3.32±1.14
mg/kg per day; n=25) to day 56 (mean 3.82±1.49 mg/kg per
day; n=17) in the benazepril group, with a mean change from
baseline of +0.50±1.40 mg/kg per day. While there were no
statistical differences between the mean values of day 0 and day
56 (both intra- or intergroup), the difference in the frusemide
dose change from baseline between the pimobendan and
benazepril groups was statistically significant (P=0.0498).
The primary variable (i.e., Heart Insufficiency Score based on
ISACHC heart failure classification) was improved in 23/27 (85%)
pimobendan/frusemide-treated dogs compared with 7/17 (41%)
benazepril/frusemidetreated dogs at the end of the 56-day treatment
period (P=0.0064; Fisher’s exact test). At day 56, an ISACHC
classification Ib (score = 2; i.e., no clinical signs) was reported for
20/27 (74%) dogs in the pimobendan/frusemide group versus 5/17
(29%) dogs in the benazepril/frusemide group (P=0.0053; Fisher’s
exact test). Differences between the groups for Heart Insufficiency
Score were statistically significant in favour of pimobendan on day
7 (P=0.0367) and day 56 (P=0.0011) [Table 3].
At the 56-day evaluation, overall efficacy was rated as very good
or good in 25/29 (86%) dogs treated with pimobendan versus
6/24 (25%) dogs treated with benazepril. Overall efficacy was
significantly higher (P<0.0001) for the pimobendan/frusemide
34
Table 3. Heart Insufficiency Score Based on ISACHC* Heart Disease Classification in the 56 Dogs on Concurrent
Frusemide Therapy
Heart Insufficiency Score*
Mean Score
Day
Treatment
Group
No.
Dogs
1
(Class Ia)
2
3
(Class Ib) (Class II)
4
(Class IIIa)
5
Median
(Class IIIb)
± SD†
P Value‡
0
Pimobendan
31
0 (0%)
0 (0%)
23 (74%)
7 (23%)
1 (3%)
3
3.29±0.5
0.5092
Benazepril
25
0 (0%)
0 (0%)
16 (64%)
8 (32%)
1 (4%)
3
3.40±0.6
Pimobendan
29
0 (0%)
16 (55%)
11 (38%)
1 (3%)
1 (3%)
2
2.71±0.9
0.0367
Benazepril
22
0 (0%)
5 (23%)
16 (73%)
0 (0%)
1 (5%)
3
3.12±0.9
Pimobendan
27
0 (0%)
20 (74%)
7 (26%)
0 (0%)
0 (0%)
2 2.61±1. 0 0.0011
Benazepril
17
0 (0%)
5 (29%)
10 (59%)
2 (12%)
0 (0%)
3
3.52±1.2
7
56
* ISACHC=International Small Animal Cardiac Health Council Score32; no. dog (percentage)
† SD=standard deviation, means and standard deviations are based on repeated measures analysis
‡ P values represent differences between pimobendan and benazepril groups for each respective day, based on repeated measures
analysis.
group (mean score 1.93±1.10; median 2.0; range 1 to 5) than
the benazepril/frusemide group (mean score 3.42±1.28; median
3.0; range 1 to 5) [Figure 1].
Results for secondary variables supported the clinical results of
the ISACHC heart failure classification. Statistically significant
differences occurred at day 56 between the two treatment
groups for exercise tolerance, demeanor, and respiratory effort
[Table 4]. No statistically significant differences were found
between the two groups at day 7 and day 56 for appetite,
coughing, and nocturnal dyspnoea. The same dogs that were
withdrawn from the total study group were also part of the
subpopulation of dogs on concurrent therapy with frusemide.
Survival analysis according to Kaplan-Meier calculations revealed
significantly prolonged survival in the pimobendan-treated dogs
(P=0.0246) [Figure 2].
While no statistically significant differences between the two
treatment groups were found regarding pulmonary oedema,
noticeable differences occurred in vertebral heart score.
Compared to baseline values of vertebral heart score, a mean
reduction in vertebral heart score was noted in the pimobendan/
frusemide group (-0.13±0.64; range -1.9 to 0.8). In the
benazepril/frusemide group, a slight increase in mean heart size
was seen (0.36±0.58; range -0.5 to 1.5), which was similar to
findings in dogs from the full study population. Differences in
mean change from baseline for vertebral heart score between
the two groups were statistically significant (P=0.0287). No
statistical differences were identified between the treatment
groups for mean FS, La:Ao, ESVI, and EDVI at day 0. Significant
differences in favour of the pimobendan group were found for
changes from baseline for FS at day 7 (P=0.0451), La:Ao at day
56 (P=0.0361), ESVI at day 7 (P=0.0022), and EDVI at day 7
(P=0.0023) and day 56 (P=0.0406) [Table 5].
Figure 3—Kaplan-Meier estimate
demonstrating the percentage of
dogs from the subpopulation of
56 dogs on concurrent frusemide
therapy surviving over time during
the long-term treatment period.
Dogs in the pimobendan treatment
group had a significantly
greater (P=0.0022) percentage
survival than dogs not receiving
pimobendan, with median survival
times being 415 and 128 days,
respectively.
Dogs were censored if they were
still alive or if withdrawal from
the study was not related to heart
failure.
35
Table 4. Scores for Secondary Variables in the 56 Dogs on Concurrent Frusemide Therapy*
Pimobendan Group (n=31)
Variable
Exercise tolerance
Demeanor
Appetite
Respiratory effort
Cough
Nocturnal dyspnoea
Benazepril Group (n=25)
Mean
Median
Range
Mean
Median
Range
P Value†
Day 0
2.45
3
1-4
2.68
3
1-4
0.4157
Day 7
2.06
2
1-4
2.40
2
1-4
0.1657
Day 56
1.87
2
1-4
2.60
2
1-4
0.0115‡
Day 0
1.71
1
1-4
2.16
2
1-4
0.0664
Day 7
1.61
1
1-5
2.20
2
1-5
0.0858
Day 56
1.61
1
1-5
2.64
2
1-5
0.0071‡
Day 0
2.29
2
1-4
2.40
2
1-4
0.7156
Day 7
2.19
2
1-4
2.48
2
1-4
0.3047
Day 56
2.16
2
1-4
2.72
2
1-4
0.0544
Day 0
2.19
2
1-4
2.16
2
1-4
0.7993
Day 7
1.61
1
1-4
2.00
2
1-4
0.1200
Day 56
1.65
1
1-4
2.36
2
1-4
0.0168‡
Day 0
2.39
2
1-4
2.44
3
1-3
0.7039
Day 7
1.94
2
1-4
2.32
2
1-4
0.0964
Day 56
2.03
2
1-4
2.52
2
1-4
0.1389
Day 0
2.30
2
1-3
2.04
2
1-3
0.2738
Day 7
1.65
1
1-3
1.76
1
1-3
0.6607
Day 56
1.61
1
1-3
2.04
2
1-3
0.0773
* See Table 1 for definitions of scoring for each variable.
† P values represent differences between pimobendan and benazepril groups for each respective day, based on repeated measures
analysis.
‡ Statistically significant
Analysis of long-term survival data demonstrated a median
survival time of 415 days for pimobendan-treated dogs versus
128 days for dogs that received no pimobendan, with KaplanMeier analysis revealing significant differences in favour of
pimobendan (P=0.0022) [Figure 3; Table 6].
of this study define that pimobendan provided a significant
advantage over benazepril in improving quality of life in affected
dogs. While subjective evaluations introduce inherent variability,
the protocol employed in this study for evaluating clinical heart
disease has been validated through other animal and human
studies that evaluated the responses of various heart diseases to
pharmaceutical intervention (e.g. ACE-inhibitors, pimobendan)
[6,7,25,26,28,34]. Although some prior studies have used the
New York Heart Association heart disease classification scheme,
both the ISACHC and New York heart classifications assess
similar clinical parameters using similar clinical interpretations,
with ISACHC taking into account the clinical nuances of heart
disease in animals [8,9,25,32]. Survival time, as defined (in this
study) by either cardiac death or cardiac treatment failure, is
a more objective assessment variable. In the study reported
here, pimobendan- treated dogs had improved overall survival
in both the 56-day and long-term study periods and higher
median survival times during the long-term treatment period.
Explanations for these improvements are rooted in recent
findings that atrioventricular valvular disease is complicated by
systolic failure much earlier than previously believed. [13] The
current therapeutic regime of using an ACE-inhibitor and/or
a diuretic can heighten the activation and negative impact of
neurohormonal compensatory mechanisms (via volume reduction
and/or hypotension), and ACE-inhibitors have been implicated in
negatively impacting myocardial function (by altering myocardial
Discussion
Clinical correlates of pharmaceutical success in the management
of heart failure secondary to atrioventricular valvular disease are
improvements in the animal’s quality and duration of life. The
results of this study demonstrated that pimobendan, compared
to benazepril hydrochloride therapy, provided statistically
significant improvements in outcomes for dogs suffering from
overt, clinical heart failure caused by atrioventricular valvular
disease. For the primary variable of Heart Insufficiency Score,
the secondary clinical study variables (i.e., exercise tolerance,
demeanor, and respiratory effort), and for the day 56 overall
efficacy evaluation, pimobendan demonstrated improvements
from baseline that were statistically better than those of the
benazepril group. At no time or for any variable measured,
did the benazepril-treated group show an advantage over
the pimobendan-treated group. All three of these assessment
modalities (ISACHC, secondary variables, and overall efficacy) are
based on subjective improvements in clinical signs and directly
relate to quality-of-life assessment; therefore, the findings
36
Table 5. Echocardiographic Parameters in the 56 Dogs on Concurrent Frusemide Therapy
Pimobendan Group
Variable
Day
Benazepril Group
(n=31)
(n=25)
P Value*
Fractional shortening (%)
Mean ± SD†
0
43.00±8.87
44.48±9.29
0.5458
Mean change vs. baseline ± SD
7
2.87±5.75
-0.12±4.98
0.0451‡
56
1.81±5.37
-0.16±6.05
0.2033
Left atrial to aortic root ratio (La:Ao)
Mean ± SD
0
2.269±0.581
2.174±0.409
0.7604
7
-0.058±0.317
-0.011±0.259
0.1528
56
-0.122±0.460
0.134±0.285
0.0361‡
2
End systolic volume index (mL/m )
Mean ± SD
0
45.3±24.4
44.5±27.6
0.7920
7
-8.4±14.4
4.6±18.7
0.0022‡
56
-4.3±12.8
5.5±19.5
0.0503
Mean ± SD
0
171.3±57.7
169.5±71.0
0.6094
7
-14.9±30.4
17.2±40.7
0.0023‡
56
-6.1±34.9
18.3±35.4
0.0406‡
2
End diastolic volume index (mL/m )
* P values represent differences between pimobendan and benazepril groups for each respective day, based on repeated measures
analysis.
† SD=standard deviation
‡ Statistically significant
congestion), but also reduction in the decline of cardiac output
and blood pressure that initiate and perpetuate compensatory
mechanisms [19,20]. In the current study, this was demonstrated
in animals via both clinical (i.e., improvements in quality of life
as evaluated by improvements in ISACHC classification) and
diagnostic (i.e. reduction in vertebral heart score, ESVI, EDVI,
and La:Ao) assessment. While not a primary study parameter,
the improvement seen in cardiac size in this study suggested
pimobendan may potentially mitigate pathological cardiac
remodelling, which warrants further investigation. Of the
cases enrolled in the study reported here, 10/41 pimobendantreated dogs and 10/35 benazepril-treated dogs did not receive
concurrent frusemide. While it may be argued that these dogs
represented asymptomatic rather than clinical atrioventricular
valvular disease, all dogs in the study were deemed to have overt,
clinical heart failure based on the findings of the ISACHC heart
disease classification (i.e., ≥ Class II), which were supported
by abnormal scores for all secondary variables and abnormal
findings on thoracic radiography and echocardiography. The
use of an ISACHC classification of ≥ Class II as a correlate of
clinical heart failure has been validated previously in dogs. [34]
The decision not to use frusemide in all dogs may have arisen
from varying opinions among veterinary cardiologists as to
the appropriateness of frusemide as a first-line therapy in mild
heart failure, and this may represent a European versus North
American difference in attitude. Regardless, when statistical
Table 6. Outcomes of the Long-Term Study Period for
the 56 Dogs on Concurrent Frusemide Therapy
Pimobendan
Group
Benazepril
Group
No. Dogs (%)
No. Dogs (%)
Total
27 (100%)
17 (100%)
Died from cardiac
dysfunction
6
(22%)
4
(23.5%)
Euthanasia from cardiac
dysfunction
3
(11%)
3
(18%)
Therapy failure
0
(0%)
4
(23.5%)
Alive
18 (67%)
6
(35%)
protein metabolism) or having their pharmacological effect
mitigated by alternate compensatory mechanism pathways
[4,11,12]. Because of its unique inodilator pharmacological
profile of acting as both a calcium sensitiser (resulting in energyneutral increases in myocardial contractility) and a peripheral
balanced vasodilator, pimobendan effectively addresses the
need for preload and afterload reduction and provides inotropic
support for systolic dysfunction. The end results are not only
improvements in early signs of reduced cardiac output (e.g.,
demeanor, exercise tolerance) and backward failure (e.g.
37
evaluations of group differences were confined to those animals
that did receive concurrent frusemide, results demonstrated a
statistical advantage to pimobendan-treated dogs in primary
variable and survival assessment, which mirrored the results of
the entire study population. Pimobendan treatment was found
to be very safe in this study, with only three dogs having side
effects associated with the drug. Initial concerns raised regarding
the potential for pimobendan to be arrhythmogenic (as with
other positive inotropes) have been unfounded, as reported in
various other human and animal studies. [27,28,35] The study
reported here has potential limitations that should be taken into
account when interpreting the results. Such limitations include
the use of ISACHC as a criterion for enrollment, the study size,
the lack of follow-up data for some variables, and the ability
to extrapolate these findings to the effects of ACE-inhibitors
as a whole. Validity of ISACHC as an enrollment/outcome
variable is not without debate because of its subjective nature.
However, the entry and exit ISACHC classifications for each
study participant were validated with the use of objective data
derived from radiography and echocardiography, and ISACHC
assessment was consistently carried out by the same evaluator
to avoid introducing interpreter variability. Based on the current
study design and the marked outcome differences between the
two treatment groups (with respect to the primary variable of
Heart Insufficiency Score and survival), the study numbers were
sufficient to statistically support the conclusion that pimobendan
was therapeutically superior to benazepril in the treatment of
overt, clinical heart failure secondary to atrioventricular valvular
disease. While increased study numbers may have allowed for
more definitive conclusions about differences between treatment
groups regarding the secondary study variables, the reality is
that if differences are small, they may not be clinically relevant.
Regardless, for none of the variables evaluated did the results
in the benazepril group exceed the results in the pimobendan
group. Lack of follow-up laboratory and ECG assessments after
inititation of therapy was also a study limitation; however, it
was never the intent of the study to evaluate these variables,
because prior studies have defined the biochemical safety
of both pimobendan and ACE-inhibitors as well as a lack of
arrhythmogenic properties for pimobendan. [9,28,35] The study
reported here specifically compared pimobendan to benazepril
hydrochloride and used the label dose for both; therefore, it
could be argued that its results cannot be extrapolated to other
ACE-inhibitors. The authors are unaware of any prior studies
that clearly define a therapeutic advantage (other than client
compliance) for one ACE-inhibitor over another; hence, it is
likely that the findings of this study are relevant to comparison
with other ACE-inhibitors as well.
with or without frusemide and an ACE-inhibitor will confer
additional improvements in outcome is unknown and requires
further study.
Acknowledgments
The authors recognize the following additional study
investigators:
Dr. Michele Borgarelli, Facoltà di Medicina Veterinaria, Grugliasco
(Torino), Italy; Dr. Oriol Domenech, Clinica Gran Sasso, Milan, Italy;
Dr. Christine Drouard-Haelewyn, Clinique Vétérinaire Roosevelt,
Mouvaux, France; Dr. Lionel Fabries, Clinique Vétérinaire de la
Croix du Sud, St. Orens de Gameville, France; Dr. Guy Gadeyne,
Dierenartsenassociatie Declercq, Marke, Belgium; Dr. Olivier
Glardon, Cabinet Vétérinaire des Jordils, Yverdon, Switzerland;
Dr. Arnaud Louvet, Clinique Vétérinaire, Saint Germain en Laye,
France; Dr. Ingrid Putcuyps, Dierenartsenpraktijk Clos Fleuri,
Gent, Belgium; Dr. Isabelle Testault, Clinique Vétérinaire Anne
de Bretagne, Nantes, France; and Dr. Andrea Vollmar, Klinik für
Kleine Haustiere, Wissen, Germany.
Footnotes
a Annex to Directive 92/18/EEC as specified in the Note for
Guidance: “Good clinical practice for the conduct of clinical
trials for veterinary medicinal products in the European
Union,” published by the European Commission in The
Rules Governing Medicinal Products in the European Union.
Vol. VII. Guidelines for the Testing of Veterinary Medicinal
Products (September 1994).
b Vetmedin; Boehringer Ingelheim Pharma KG, Ingelheim,
Germany
c Fortekor; Novartis Tiergesundheit GmbH, Eschborn,
Germany
d SAS version 8.2; SAS Institute, Inc., Cary, NC 27513-2414
e TESTIMATE version 6; IDV, Gauting, Germany version 6; IDV,
Gauting, Germany
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with or without frusemide. Based on these results, pimobendan
should be considered as a primary treatment modality when
atrioventricular valvular disease progresses to overt, clinical
heart failure. Whether or not the combination of pimobendan
[6]
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Notes for contributors to ejcap
Information relating to material to be directly submitted for
Publication in EJCAP can be found as follows:
39
•
FECAVA WEBSITE
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IN EJCAP
EJCAP 16(2) p. 210
UROGENITAL SYSTEM
REPRINT PAPER (A)
Intra-abdominal testicular
torsion in a cryptorchid dog
G. Gradner(1), D. Dederichs(1), K.M. Hittmair(2)
SUMMARY
A 4.5 year old cryptorchid male Greyhound was presented with abdominal pain at the emergency service of the
Vienna University of Veterinary Medicine. Palpation revealed a painful mass with a diameter of 10 cm located cranial
to the urinary bladder. Abdominal ultrasonography showed torsion of the left testicle. Both retained abdominal testes
were removed at emergency surgery. A Sertoli cell tumour had diffusely infiltrated the tissue of the larger testicle.
Keywords Spermatic cord torsion, Sertoli cell tumour, cryptorchidism, dog.
According to the owner´s information, the 4.5 year old male
Greyhound had been imported from Spain a year before as a
supposedly castrated and fully vaccinated dog. The animal had a
history of mitral valve fibrosis and pyoderma. Two days prior to its
presentation at the clinic, the dog had started showing reluctance
to move, lethargy and reduced appetite. Water intake was normal.
Ultrasonography
Abdominal ultrasonography showed a mildly enlarged prostate
with heterogenous, hyperechoic tissue. The retained right testicle
was detected caudal to the kidney and cranial to the urinary
bladder; it was oval in shape, 3 cm in diameter and hypoechoic
with a hyperechoic rete testis (Fig. 1). Slightly left of midline a 10
cm mass of mixed echogenicity was visualised (Fig. 2). From this
mass, a hyperechoic cord extended caudally, showing markedly
dilated and tortuous blood vessels (Fig. 3). No connection with
any other abdominal organ could be observed. Neoplasia of the
left intra-abdominal testis with suspected testicular torsion was
diagnosed.
Clinical examination and laboratory tests
On presentation the dog´s general condition was mildly
depressed and the rectal temperature was 38.9°C. The pulse
had a moderate quality at a rate of 120 beats per minute. The
respiratory rate was 32/minute. The dog´s mucous membranes
were brick-red and capillary refill time was delayed (>2 seconds).
Auscultation of the heart revealed a II/IV holosystolic murmur.
Pulmonary auscultation was unremarkable and the peripheral
lymph nodes were normal. Palpation of the caudal abdomen
was extremely painful and revealed a mass of about 10x10 cm
in the left caudal quadrant.
The dog exhibited a stiff gait, particularly in the hind limbs,
and was reluctant to stand. Haematology revealed leukocytosis
with 19,070/µl (reference 6,000-15,000/µl), the differential
count showed 6.7% monocytes, 7.9% lymphocytes and 84.4%
granulocytes. Other blood parameters (red blood cell count,
blood chemistry) were normal.
Surgical treatment
Prior to surgery, the patient was stabilised with Ringer´s
solution at a rate of 4 ml/kgBm/h i.v. (Ringerlactat®, 10 ml/kg/h
intraoperative dose, Fresenius, Graz) and intravenous antibiotic
therapy (Cefazolin Sandoz®, 20 mg/kg, Sandoz GmbH, Kundl).
Methadone (Heptadon®, 0.1 mg/kg, EBEWE Pharma GesmbH,
Unterach) and acepromazine (Vanastress®, 0.02 mg/kg, Vana
gmbH, Vienna) were administered as premedication. Induction
of anaesthesia was performed using propofol (Propofol 1%
Fresenius®, 0.1 mg/kg, Fresenius Kabi, Graz). After intubation,
anaesthesia was maintained with isoflurane (Isofluran®, 1-2
vol.%, Abbot Laboratories Ltd., Kent, UK) and fentanyl (FentanylJanssen®, drip infusion, 20-40 µg/kg/h, Janssen, Vienna). Ventral
coeliotomy was chosen as an approach to the abdomen, making
a midline skin incision from the umbilicus to the pubis. A minimal
quantity of serosanguineous fluid was removed by suction and
the left testicle was localised parasagittally in the mid-abdomen.
Wien.Tierarztl.Masch.* (2006) 93, p 58-61
Case report
(1) Department of Small Animals and Horses, (Clinic of Surgery and Ophthalmology) and the Radiology Clinic.
(2) Department of Diagnostic Imaging, Infectious and Laboratory Medicine, Vienna University of Veterinary Medicine, A-1210 Veterinarplatz 1, Vienna
E-mail: [email protected]
*Presented by VÖK (Austria)
41
Intra-abdominal testicular torsion in a dog - G. Gradner
Fig. 1: Ultrasonogram, sagittal scan: abdominal right testis;
hypoechoic tissue; rete testis appears as a hyperechoic line (arrow);
bowel loops are visualised distal to the rete testis.
Fig. 2: Transverse sonogram: neoplastic abdominal left testicle;
mixed echogenicity, heterogenous tissue.
The spermatic cord had undergone a clockwise rotation of more
than 360°, about 4 cm proximal to the testicle. The testis was
extremely enlarged showing a haemorrhagic infarct (Fig. 4).
The testicular artery and vein as well as the ductus deferens
were ligated separately using monofilament absorbable suture
material (Monosyn 2/0). The right undescended testicle appeared
atrophied and was removed in the same manner (Fig. 5). After
rinsing the abdominal cavity with Ringer´s solution at body
temperature and careful inspection for haemorrhage, closure of
the linea alba and the subcutaneous tissue was performed with
simple interrupted sutures using monofilament absorbable suture
material. The skin was closed with monofilament nonabsorbable
suture material using a simple interrupted suture pattern.
was uneventful and the dog was discharged from the clinic
the day after surgery. Further medical management included
oral antibiotics (Cephalobene®, 20 mg/kg BM BID, Ratiopharm,
Vienna) for 5 more days and tramadole 2 mg/kg BM BID as an
analgesic (Tramal retard 50 mg®, 2 mg/kg, Grünenthal GesmbH,
Brunn a. Gebirge). The dog was presented for a follow-up
examination and removal of sutures ten days following surgery.
The surgical wound had healed, and the patient was clinically
unremarkable.
Histopathology
The left testicle was diffusely infiltrated by a Sertoli cell tumour.
For the most part, the tissue was necrotic and characterised
by a severe haemorrhagic infarct in conjunction with multiple
ischaemic necrotic foci.
Histology of the HE-stained tissue sample harvested from
the tumour showed pale cylindric neoplastic cells of tubular
alignment. Tumour cells may either consist of mixed cell types or
present as large cells (THOMAS, 1998).
Postoperative management
Fluid therapy with Ringer´s solution was continued for another
24 hours postoperatively at a rate of 4 ml/kg BM/h. Analgesia
was maintained with methadone (Heptadon®, 0.1 mg/kg BM)
administered every four hours. Antibiotic therapy was continued
by intravenous administration of cefazoline (Cefazolin Sandoz®,
20 mg/kg BID) at the indicated dose. The patient´s recovery
Discussion
Fig. 3: Sagittal sonogram: Colour flow Doppler image of the intraabdominal left spermatic cord; congested blood vessels indicative of
torsion of the left testis.
Clinical symptoms of an abdominal testicular torsion include
anorexia, lethargy, vomiting, diarrhoea, swelling of the scrotal and
inguinal area, stiff gait and a painful abdominal mass. Symptoms
are non-specific and other causes of an acute abdomen such as
ileus, prostatitis, prostatic carcinoma, prostatic cysts, peritonitis,
pancreatitis, urethral obstruction, acute pyelonephritis, splenic
torsion, testicular torsion, testicular tumour and tumours of
the urinary bladder must be considered as possible differential
diagnoses.
While intrascrotal testicular torsion in human males is extremely
painful and is always considered an emergency, dogs appear
to feel less pain on palpation (HULSE, 1973; ZYMET, 1975). In
dogs, the condition causes not only gastrointestinal symptoms,
but also a stiff gait (YOUNG, 1979). In young men, intrascrotal
testicular torsion presents as a severely painful, acute swelling of
the scrotum (MINEVICH, 2002). If the condition is not resolved
surgically within six hours, there is a risk of irreversible impairment
of the blood supply to the testis (LÖHMER and TRYBA, 1999).
42
dogs than in dogs with normally descended testes (ROMAGNOLI,
1991). Some breeds show a higher incidence of cryptorchidism:
Toy Poodles, Pomeranians, Yorkshire Terriers, Dachshunds and
Cairn Terriers seem to be overrepresented (ROMAGNOLI, 1991).
Parents of cryptorchid puppies must be excluded from breeding.
While unilateral cryptorchids show normal spermatogenesis,
bilateral cryptorchids are usually sterile (MEMON and TIBARY,
2001). Anecdotal reports describe that hormonal treatment using
androgen and gonadotropin induced descent of the testes in dogs
(ROMAGNOLI, 1991). Since the inguinal canal of dogs with intraabdominal cryptorchidism is fully obliterated, this treatment may
only be successful in cryptorchids where the undescended testis
is located within the inguinal canal (ROMAGNOLI, 1991). The
abdominal temperature in the undescended testicle is ideal for
the development of a Sertoli cell tumour, since only Sertoli cells
and interstitial cells remain intact, while all tubular germinative
epithelia are destroyed and their endocrine function is lost due
to the higher temperature (BOOTHE, 2003). Approximately 59 %
of dogs with Sertoli cell tumours develop clinical symptoms such
as bilateral alopecia, which starts in the inguinal area and then
spreads over the entire ventral abdomen (HARARI and SMITH,
1983). Hyperpigmentation and feminization may also develop
due to the production of oestrogens and steroids (LANG et
al., 1983). Haematological changes such as pancytopenia and
bone marrow hypoplasia may also be present (MADEWELL and
THEILEN, 1987).
Fig. 4: Intra-operative photograph of the left testicle with the
twisted spermatic cord.
In human medicine, radionuclides such as technetium are used
diagnostically to evaluate testicular blood flow, by differentiating
between testicular torsion and epididymitis, the most important
differential diagnosis in men (AZMOUN, 1995). Scrotal testicular
torsion is very rarely observed in dogs, with only five cases
described in the past 50 years (HULSE, 1973; PEARSON and
KELLY, 1975; ZYMET, 1975; YOUNG, 1979). In his doctoral thesis
about palpation findings of the canine scrotum, testicles and
epididymes in relation to the dog´s body mass, KOWALZIK (1991)
reports that 1.5 % of the examined dogs showed reversible
intrascrotal testicular torsion. Intra-abdominal testicular torsions
occur more frequently but are still unusual in the dog (PEARSON
and KELLY, 1975; OFNER, 1982; KOCH et al., 1997; REIF et al.,
2001; BARTLETT, 2002; HECHT et al., 2004).
Intra-abdominal testicular torsion is extremely rare in men; but
in dogs it commonly results from neoplastic enlargement of
the testis (WIGGER et al., 2004). The course of the disease can
be acute or chronic (PEARSON and KELLY, 1975). HECHT et al.
(2004) describe the sonographic diagnosis of a non-neoplastic
torsioned intra-abdominal testicle in a dog. Due to the long
testicular mesentery, the intra-abdominal position of the testis
allows increased mobility of the gonad. With additional neoplastic
enlargement the testicle becomes heavier and rotation will
occur much more easily than within the scrotum (WIGGER et al.,
2004). In some cases of testicular torsion, necrotic degeneration
of the tissue is so severe that it is impossible to clearly identify
neoplasia (KOCH et al., 1997).
In our patient, cryptorchidism was diagnosed using ultrasonography and diagnostic laparotomy. Testicular torsion
should be considered as the main differential diagnosis in all
cryptorchids with abdominal pain. Because of the genetic basis
of cryptorchidism and the increased risk for developing testicular
neoplasia and testicular torsion, affected animals should be
castrated within the first year of life.
Acknowledgements
The authors would like to thank the Department of
Anaesthesiology and Intensive Medicine as well the Institute of
Pathology and Forensic Veterinary Medicine for their support.
Fig. 5: Comparative illustration of both surgically removed
testicles: Note the atrophied right testis and the neoplastic left
testis with its altered tissue and the haemorrhagic infarct
Cryptorchidism is a genetic defect. Unilateral cryptorchids,
however, are fully fertile and pass the defect on to future
generations. The probability of developing unilateral
cryptorchidism varies between 1% and 15%; this means that
the risk of testicular neoplasia is 9.6 – 13.6 times higher in these
43
Intra-abdominal testicular torsion in a dog - G. Gradner
References
AZMOUN (L.) - Testicular torsion. http://brighamrad.harvard. edu/
Cases/bwh/hcache/125/full.html; letzte Einsichtnahme, 1995,
2005-09-20
BARTLETT (G.R.) - What is your diagnosis? Self Assessment. J. Small
Anim. Pract., 2002, 43: 551-552
BOOTHE (H.W.) - Testes and epididymides. In: SLATTER, D. (ed.):
Textbook of small animal surgery. 3rd ed., vol. 2, Saunders,
Philadelphia, 2003, p. 1521-1530
HARARI (J.H.), SMITH (C.W.) - Spermatic cord torsion and sertoli cell
tumor in a dog. JAVMA, 1983, 183: 879-881
HECHT (S.), KING (R.), TIDWELL (A.S.), GORMAN (S.C.) - Ultrasound
diagnosis: intraabdominal torsion of a non-neoplastic testicle in a
cryptorchid dog. Vet. Rad. & Ultrasound, 2004, 45: 58-61
HULSE (D.A.) - Intrascrotal torsion of the testicle in a dog. Vet. Med.
Small. Anim. Clin., 1973, 68: 658-659
KOCH (H.), SOHNS (A.), SCHEMMEL (U.), DOERING (K.) - Torsio testis
bei einem abdominalen kryptorchiden Pitbullterrier-Rüden.
Kleintierpraxis, 1997, 42: 151-152
KOWALZIK (A.) - Palpatorische und metrische Befunderhebung an
Skrotum, Hoden und Nebenhoden des Hundes unter besonderer
Berücksichtigung des Körpergewichtes sowie der Diagnostik.
Dissertation, Tierärztliche Hochschule Hannover, 1991
LAING (E.J.), HARARI (J.), SMITH (C.W.) - Spermatic cord torsion and
sertoli cell tumor in a dog. JAVMA, 1983, 183: 879-881
LÖHMER (), TRYBA (M.) - Notfälle aus der Urologie. In: HEMPELMANN,
G., ADAMS, H.-A., SEFRIN, P. (Hrsg.): Notfallmedizin. Bd.3,
Thieme, Stuttgart, 1999, S. 218-219
MADEWELL (B.R.), THEILEN (G.H.) - Tumors of the genital system. In:
THEILEN, G.H., GORDON, H. (eds.): Veterinary cancer medicine.
2nd ed., Lea&Febinger, Philadelphia, 1987, p. 594
MEMON (M.), TIBARY (A.) - Canine and feline cryptoridism.
www.ivis.org; letzte Aktualisierung 2001-07-01, letzte
Einsichtnahme, 2005-05-10
MINEVICH (E.) - Testicular torsion. http://www.emedicine.
com/med/topic2780.htm; letzte Aktualisierung 2002-10-04,
letzte Einsichtnahme, 2005-09-22
OFNER (W.) - Kryptorchismus und Hodentorsion beim Hund. Wien.
Tierärztl. Mschr., 1982, 69: 368
PEARSON, (H.), KELLY, (D.F.): Testicular torsion in the dog: a review of
13 cases. Vet. Rec. 1975, 97: 200-204
REIF (U.), WALSHAW (R.), PERRY (R.) - Urethradivertikulum,
persistierendes Urachusligament und Hodentorsion bei einem
kryptorchiden Hund. Kleintierpraxis, 2001, 46: 733-739
ROMAGNOLI (S.) - Canine cryptorchidism. Small Anim. Pract. 21, 1991,
533-542
THOMAS (C.) - Histopathologie. 13.Aufl., Schattauer, Stuttgart, 1998,
S. 225
WIGGER (A.), KRAMER (M.), PEPPLER (C.), JAWINSKI (S.) - Testicular
torsion in the dog. Kleintierpraxis, 2004, 49: 563-569
YOUNG (A.C.B.) - Two cases of intrascrotal torsion of a normal testicle.
J. Small Anim. Pract., 1979, 20: 229-231
ZYMET (C.L.) - Intrascrotal testicular torsion in a sexually aggressive
dog. Vet. Med. Small Anim. Clin., 1975, 70: 1330-1331
UROGENITAL SYSTEM
REPRINT PAPER (B)
True hermaphroditism in six female
littermates after administration of
synthetic androgens to a pregnant bitch
H. de Rooster (1), G. Vercauteren(1), K. Görtz(1), J. Saunders(1), I. Polis(1), T. Rijsselaere(1)
SUMMARY
A pregnant bitch was treated with a synthetic testosterone mixture around day 40. The female offspring (6 pups)
showed an increased anogenital distance, vaginal enlargement and a variable amount of vaginal discharge.
The urinary orifice was found dorsally in the vestibulum, mounted on a protruding phallus like structure.
All six pups underwent a laparotomy and subsequent spaying, and a modified ventral episioplasty technique to lift
up the labia to a more vertical position in order to prevent urine accumulation. Histopathologic examination of the
genital tracts demonstrated the presence of bilateral ovotestes and remnants of the Wolffian duct system in all cases.
The finding of true hermaphroditism of the offspring after exogenous androgen administration during gestation
of the bitch has not yet been reported elsewhere.
the puppies were 3 weeks old because the breeder considered
surgical correction of the enlarged genitalia. All puppies were
examined at the Department of Small Animal Surgery at the
age of 5 weeks. The littermates had a uniform body weight
and size. The only male puppy showed no visible abnormalities.
Both testicles were present in the scrotal region. All females
showed an anogenital distance longer than normal compared to
females of the same breed and age. A similar degree of vaginal
enlargement with a variable amount of vaginal discharge was
present. The urinary orifice was found dorsally in the vestibulum,
mounted on a protruding phallus like structure which was slightly
hypospadic. The urethral groove was V-shaped without a dorsal
roof of urethral mucosa, the opening being only large enough
to pass an 8 French Foley catheter. Ventral to the osteum, the
ventral mucosa had the appearance of a normal vestibulum and
no enlarged clitoris could be appreciated. No scrota were present.
The nipples were present in normal number and position. One
puppy had a discrete umbilical hernia. No other abnormalities
were observed.
Surgical correction was postponed a few weeks, to decrease
anaesthetic risks. The female puppies were reassessed at the age
of 9 weeks. The clinical exam did not reveal any abnormalities
except for vaginitis and enlarged external genitalia. The urethral
opening could be extruded out to a variable length (1 to 2 cm)
and the tip curled up dorsally (Fig.1B).
All the pups were submitted to a complete abdominal
ultrasonographic examination. The abdomen was prepared
by clipping the hair, acoustic gel was applied and the pups
were positioned in dorsal recumbency. The examination was
Reprod. Dom. Anim.* (2006) 41 p22-26
A three-year-old female American Staffordshire Terrier
was presented to a private practitioner because of severe
pseudopregnancy. The bitch was treated with oestradiolbenzoatea and oral bromocryptineb. Ovariohysterectomy was advised
because the pseudopregnancy recurred during every cycle.
Two months later, the bitch was again lactating. The practitioner
falsely diagnosed recurrence of pseudopregnancy and tried to
convince the owners not to postpone the ovariohysterectomy
any longer. The medical treatment was an injection of a
mixture of synthetic androgensc instead of oestradiolbenzoate
because of the possibility of bleeding disorders after repeated
administration of oestrogens.
Three weeks later, the bitch was still producing a lot of milk and
the abdomen had gradually increased in size. Relaxin testingd
revealed a positive gestation result.
Four days later, the bitch gave birth to 8 puppies. One extremely
small male puppy with everting small intestines through an
umbilical herniation died almost immediately. The remaining
puppies were 1 male and 6 females. All the female puppies
showed a ventral displacement of the vaginal orifice and labia
(Fig.1A).
The Department of Reproduction, Obstetrics and Herd Health
of Ghent University Veterinary Hospital was contacted when
(1) Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke E-mail: [email protected]
* Presented by SAVAB (Belgium)
45
True hermaphroditism in six female littermates after administration of synthetic androgens to a pregnant bitch - H. de Rooster
Fig.1 External genitalia of the female offspring. A. The vagina and labia are ventrally displaced and enlarged.
B. A phallus like structure could be extruded out through the labia, the tip curled up dorsally.
performed with a linear 7-12 MHz matrix transducere. The left
gonad had a mean length of 10.8mm (from 9.9 to 10.9) and a
mean height of 4.7mm (from 4.2 to 5.4) and the right gonad a
mean length of 10.6mm (from 9.7 to 11.3) and a mean height of
4.3mm (from 3.9 to 4.7). Both gonads were homogeneous. The
gonads were hypoechogenic compared to the medulla of the
kidneys in 4 pups and were slightly hyperechogenic in 2 dogs.
The cervix was homogeneous, located ventrally to the colon and
latero-dorsally to the urinary bladder. It measured 4.6mm (from
0.38 to 0.55mm) in diameter.
A radiographic study was performed in one pup to confirm the
absence of abnormalities from the urethra and vagina. Plain
abdominal radiographs (right-left lateral and ventro-dorsal)
were taken and showed no abnormalities. Vaginourethrocystography was performed on the same pup using a previously
described technique and was also normal.
The uterus had the same anatomical structure as in a normal
developed bitch and consisted of two uterine horns, one
uterine body, the mesometrium, the round ligament and the
cervix. Along the medial side of both uterine horns a thin white
filamentous structure was visible which convened at the top
of the uterine body (Fig.2.2). Another filamentous structure
originated halfway along each uterine horn and passed into the
inguinal ring (Fig.2.3). This ligament had a similar appearance to
a ductus deferens, yet not aligned by prominent blood vessels.
A routine ovariohysterectomy was performed: the ovarian pedicle
was ligated twice after which the ovarian bursa was opened
and the pedicle was transected. The mesometrium was divided
into two parts and each part was ligated once. Subsequently,
the uterine body was ligated twice and amputated near the
cranial border of the cervix. All ligations were performed with
Polyglactin 910n. The abdominal incision was closed in a routine
manner.
To treat the signs of vaginitis, a ventral reconstructive procedure
(ventral episioplasty) was performed to lift up the labia to a more
vertical position in order to prevent urine accumulation (Fig.3).
Therefore a sufficient area of skin was resected from the ventral
surface of the vestibulum. The first incision initiated lateral to
the dorsal commisure of the vulva, proceeded ventrally, and
continued to the opposite side. The second incision started at
the same point as the first, but extended in a wider arc outlining
the segment of skin to be removed. The skin was excised without
perforating the vestibular lumen. The skin edges were apposed
by placing simple interrupted sutures of polyamideo starting at
the 6-o’clock position.
Recovery was uneventful and all puppies were eating again 4
hours after surgery.
No postoperative complications were detected. The puppies were
discharged the next day and no medication was prescribed, except
for one puppy in which treatment with antiseptic vaginal douches
of 0.05% chlorhexidine were advised twice daily for one week.
Two of the puppies could be reassessed 14 days after the
corrective procedures. The owner reported an uneventful
recovery without any urinary problems. No signs of vaginal
discharge were visible at examination. Both surgical scars had
healed by primary intention. Another puppy was represented 3
months postoperatively for unrelated problems. The distal ending
of the urethra could intermittently be seen, protruding slightly
Surgery
The animals were fasted and deprived from water for 6 hours
before surgery. Premedication was performed intravenously with
a mixture of 0.2mg/kg midazolamf and 0.1mg/kg methadoneg.
Propofol at a dosage of 5mg/kg IV was used for induction. All
dogs were intubatedh and anaesthesia was maintained with
isofluranei in 1L/min of oxygen using a circle anaesthetic systemj.
Monitoring consisted of multi-gas analysis, pulse-oximetry, and
ECGk. Additional peri-operative analgesia was provided by a
lumbosacral epidural injection of lidocainel and morphinem.
The ventral abdomen and the perineal region were clipped
and prepared for aseptic surgery. A midline laparotomy was
performed, extending from the umbilicus up to the pubic bone.
The whole abdomen was thoroughly explored for congenital
abnormalities. All organs, except from the reproductive tract,
appeared normal. All abdominal findings were identical for
each female puppy (Fig.2). The reproductive tract consisted
of bilateral gonads that are located just caudal to the poles of
each kidney and covered by an ovarian bursa like structure. At
the ventral opening of each bursa a tortuous structure could
be recognized macroscopically (Fig.2.1). The gonads were fixed
to the transversalis fascia by a small ligament adjacent to a
vein and artery which supplied the gonad and together they
were covered with a small amount of fatty tissue. Furthermore,
each gonad was attached by a ligament to the uterine horn.
46
Fig.2 Female reproductive tract.
1. Uterine tube (oviduct).
2. Filamentous structure along the medial side of both uterine
horns which convened at the top of the uterine body.
3. Filamentous structure along the distal half of the lateral side of
both uterine horns which passed into the inguinal ring (ductus
deferens).
Fig.3 Ventral episioplasty.
A horse-shoe area of skin was resected from the ventral surface of
the vestibulum.
serosa. These tubules were histologically identical to oviduct
tissue. Gonadal immunohistochemical reactivity for oestrogen
and progesterone receptor was similar to that observed in
normal canine immature ovaries. Since both ovarian and
testicular components are present, the gonads of all puppies
are determined as ovotestes. The uterus showed the histological
characteristics of a normal immature canine uterus: its lumen
was lined by a cylindrical epithelium and the underlying stroma
contained few endometrial glands, muscularis and serosa were
also completely comparable. Immunohistochemical reactivity
for oestrogen receptor and progesterone receptor was similar
to that observed in normal canine immature uteri. The tubules
protracting laterally along the uterine horns and corpus uteri were
strongly convoluted. They were thick walled, possessed lumens
and lined by a ciliated cylindrical epithelium. A large portion
of the wall consisted of different layers of tunica muscularis.
According to their histological properties, the tubules along the
lateral side of both uterine horns can be designated as ductus
deferens (Fig 5).
The thin filamentous structures arising halfway down both
uterine horns on the medial side were composed of a central
core of adipocytes surrounded by a thin layer of fibrous tissue.
At the apposition site with the uterine serosa, the filament was
thickened by a cluster of smooth muscle cells.
out of the vulva. No discharge nor excessive licking was reported.
The remaining owners were contacted by phone 4 months after
the surgery. They were all pleased with the operative result and
recovery of their pet. Although the external genitalia were still
visibly enlarged, none of the owners considered this to be a
problem.
Histopathology
Of all six puppies, the gonads, uteri and the tubular structure
medial and lateral from the uterine horns were formalinp
fixed, paraffin wax embedded and sectioned at 4µm. All
sections were haematoxylin and eosin stained. All samples
were additionally examined immunohistochemically using a
standard avidin biotin complex method with diaminobenzidine
as chromogen. Dewaxed tissue sections were incubated with
mouse monoclonal anti-human oestrogen receptorq and mouse
monoclonal anti-human progesterone receptorr according to
the manufacturer’s instructions. Normal juvenile canine male
and female reproductive tracts served as controls. Subsequently,
all tissue sections were microscopically examined.
Histological characteristics were similar for all puppies (Fig.4
and 5). The gonad was lined by a cuboidal surface epithelium.
In a narrow band of cortical stroma, scattered clusters of
primordial follicles with primary oocytes, comparable to those
of normal immature ovaries, were present (Fig.4.1). In the
medullary stroma, multiple tubular structures with a prominent
basement membrane were observed. The tubules had small
lumens and composed of large columnar to triangular cells
with an abundant amount of pale cytoplasm and a basal
round nucleus with an inconspicuous nucleolus. The gonadal
medullary tubular structures were histologically identical to
immature seminiferous tubules with immature Sertoli cells
(Fig.4.2). No germ cells were observed. At the gonadal hilus,
several sections (implicating their convoluted nature) through
large arteries and veins were present. The tubules arising at the
gonadal hilus possessed long, slender mucosal folds lined by a
ciliated columnar epithelium, a thin muscularis and a prominent
Discussion
In carnivores, indications for testosterone administration are
sparse due to the multiple side-effects. Testosterone is known
to stimulate development of the mammary glands when used in
small doses whereas it inhibits the secretion of milk and inhibits
follicular growth in higher doses and it may induce mild to
severe external masculinisation of the bitch (Olson et al. 1986;
Concannon and Meyers-Wallen 1991). In the present clinical
report, the pregnant bitch was given a high dose of androgens
because the private practitioner falsely suspected recurrence of
pseudopregnancy.
Androgen administration during gestation is known to result
in varying degrees of masculinisation of the female offspring
(Curtis and Grant 1964; Neumann et al. 1969; Shane et al.
1969; Biewenga et al. 1975; Meyers-Wallen and Patterson
47
True hermaphroditism in six female littermates after administration of synthetic androgens to a pregnant bitch - H. de Rooster
Fig.4 Ovotestis. Gonadal cortex and superficial medulla showing 1.
Primordial follicles with primary oocytes and 2. Seminiferous tubules
with immature Sertoli cells. (HE, Bar = 100μm)
Fig.5 Ductus deferens arising halfway along the uterine horn.
(HE, Bar = 200μm)
1986; Nickel 1996; Feldman and Nelson 2004). The disturbance
of sexual differentation depends upon the stage of embryogenic
development, the kind of agent, the amount and the pathway
of administration, and the duration of its use (Neumann et
al. 1969; Shane et al. 1969; Biewenga et al. 1975). In female
foetuses, the greatest sensitivity to exogenous androgens is
shown by the epithelium of the urogenital opening (Neumann
et al. 1969).
Different types of gender can be defined. For the diagnosis of
gonadal gender, gross as well as histologic examination of the
gonads is essential (Meyers-Wallen and Patterson 1986). The
phenotypic gender is determined both by the internal and external
genitalia (Meyers-Wallen and Patterson 1986). Determination of
the genetic gender should be made by chromosome analysis on
cells from several tissues (Hare 1976).
Sex differentation in foetuses takes place in three sequential
events that occur prenatally. Successively the gonads, the genital
duct system and the urogenital opening and external genitalia
are involved (Hare 1976; Grumbach and Ducharme 1960). In
contrast to the development of the ductal systems, in placental
mammals, the development of the indifferent gonads towards
testes or ovaries can be scarcely influenced experimentally
(Biewenga et al. 1975). It is often stated that steroidal hormones
have no effect at all on gonadal differentiation in the female
offspring (Grumbach and Ducharme 1960; Curtis and Grant
1964; Neumann et al. 1969; Shane et al. 1969; Wentinck et
al. 1973; Rothuizen et al. 1978). Histopathologic examination
of all genital systems of the female pups under consideration,
however, proved the existence of bilateral ovotestes in all
cases. This makes the offspring true hermaphrodites instead
of female pseudohermaphrodites as reported in previous
cases of androgen administration (Curtis and Grant 1964;
Neumann et al. 1969; Hare 1976; Meyers-Wallen and Patterson
1986; Nickel 1996; Feldman and Nelson 2004). [3,4,7-10] The
presence of both testicular and ovarian tissue can be looked
upon as incomplete masculinisation at the time of gonadal
differentation. A survey study in 1976 revealed 13 reported
isolated cases of true hermaphroditism in dogs, none for which
a specific causal explanation could be given (Hare 1976). A later
study of a large family of American Cocker Spaniels identified
9 more true hermaphrodites, verifying it can be a genetically
determined form of intersexuality (Selden et al. 1984). In
the present study, the synthetic testosterone mixture was
administered parenterally around day 40, if an average gestation
length of 65 days is considered (Concannon et al. 1983). The
onset corresponds to the priming period found in the literature
for female canine foetus to be influenced by androgens which
lies between 28th and 42rd day of gestation (Curtis and Grant
1964; Shane et al. 1969; Biewenga et al. 1975). On the other
hand, it is relatively late in the course of gestation, and one
would have expected the sex differentation of the gonads to
have been determined at that point. The finding of ovarian as
well as testicular components in the gonads was therefore very
surprising. The mechanism as to whether testicular or ovarian
tissue will dominate in the bipotential corticomedullary gonad
is still not fully understood (Hare 1976). On the other hand, it
has been impossible experimentally to modify the development
once differentation or regression has been determined (Shane
et al. 1969). No explanation for our observations of ovotestis
can be given.
In normal female foetuses, the Müllerian ductal system develops
whereas the Wolffian ducts completely or almost completely
disappear (Curtis and Grant 1964; Shane et al. 1969; Wentinck
et al. 1973; Biewenga et al. 1975; Hare 1976). The presence
of functional foetal testes results in stimulation of the Wolffian
ducts and regression of the Müllerian ducts, and also initiates
the development of the accessory glands and penis at the level
of the urogenital opening (Biewenga et al. 1975; Hare 1976).
However, according to Hare (1976), the presence of excessive
(exogenous or endogenous) circulating androgens neither
stimulates the Wolffian ducts nor induces regression of the
Müllerian ducts. It only causes masculinisation of the urogenital
sinus and external genitalia. Nevertheless during laparotomy
Müllerian duct derivatives (uterus and cranial vagina) as well
as Wolffian duct derivatives were seen (epidydimis and ductus
deferens). These macroscopic findings could be confirmed
histopathologically.
Regardless of the degree of masculinisation of the gonad,
a normal size and appearance of the uterus is a known
phenomenon in dogs (Meyers-Wallen et al. 1987). This is in
48
References
perfect agreement with the findings for this case of normal
oviduct, uterus and cervix.
In most reported cases of female pseudo- or true hermaphrodism,
clitoral enlargment is the most common physical finding (MeyersWallen and Patterson 1986). The phallic structure is determined
to be a clitoris if found on the ventral floor of the vagina and
when the urethral meatus is not contained within the clitoris
(Meyers-Wallen and Patterson 1986). In the present study, the
urethral meatus of all pups was consistently found at the tip of a
penislike structure instead of in the ventral vagina.
Contrast studies were done to conform the absence of
morphological abnormalities of the urinary bladder, urethra and
vagina. A retrograde positive-contrast vagino-urethrography is
the recommended procedure to evaluate these structures while
ultrasonography is the method of reference for the examination
of the canine ovaries and uterus. The ultrasonographic
appearance of the ovary through the oestrus cycle in the normal
bitch has been described. In the present case, the aspect of the
gonads was compatible with a normal anoestrus ovary (England
and Yeager 1993).
Episioplasty is a reconstructive procedure, most commonly
used for the treatment of perivulvar pyoderma in obese bitches
in which excess dorsal skin folds are excised (Greene 1983;
Lightner et al. 2001). To deal with the signs of vaginitis, the
resorted episioplasty procedure was modified to avoid pooling
of urine in the ventral vagina. In males, a similar technique of
preputial shortening is described to prevent urine pooling in the
prepuce (Hosgood and Hoskins 1998). In these cases, however,
a full-thickness section of preputial skin and mucosa is resected.
The authors resected skin and nevertheless achieved a succesful
outcome.
Urinary incontinence, which has been associated with female
pseudohermaphroditism due to pooling of urine in the vagina
or uterus (Rothuizen et al. 1978; Meyers-Wallen and Patterson
1986; Nickel 1996), was not reported by the puppy owners in
this case.
BIEWENGA (W.J.), OKKENS (A.C.), WENSING (J.G.) - Anabolica – Soms
riskant. Tijdschr Diergeneesk, 1975, 100:391-392.
CONCANNON (P.), WHALEY (S.), LEIN (D.), WISSLER (R.) - Canine
gestation length: variation related to time of mating and fertile
life of sperm. Am J Vet Res, 1983, 44:1819-1821.
CONCANNON (P.W.), MEYERS-WALLEN (V.N.) - Current and proposed
methods for contraception and termination of pregnancy in dogs
ans cats. J Am Vet Med Assoc, 1991, 198:1214-1225.
CURTIS (E.M), GRANT (R.P.) - Masculinization of female pups by
progestogens. J Am Vet Med Assoc, 1964, 144:395-398.
ENGLAND (G.C.W.), YEAGER (A.W.) - Ultrasonographic appearance of
the ovary and uterus of the bitch during oestrus, ovulation and
early pregnancy. J Reprod Fertil Suppl, 1993, 47:107-117.
FELDMAN (E.C.), NELSON (R.W.) - Vaginal defects, vaginitis, and
vaginal infection. In: Feldman EC, Nelson RW (eds), Canine and
feline endocrinology and reproduction. 3rd ed. WB Saunders Co
St-Louis, 2004, pp. 901-918.
GREENE (J.A.) - Vagina and vulva. Episioplasty. In: Bojrab MJ (ed),
Current techniques in small animal surgery. 2nd ed. Lea & Febiger
Philadelphia, 1983, pp. 355-357.
GRUMBACH (M.M.), DUCHARME (J.R.) - The effects of androgens on fetal sexual development. Androgen-induced female
pseudohermaphrodism. Fertil Steril, 1960, 11:157-180.
HARE (W.C.D.) - Intersexuality in the dog. Can Vet J, 1976, 17:7-15.
HOSGOOD (G.), HOSKINS (J.D.) - Urogenital disorders. Penile
amputation. In: HOSGOOD (G.), HOSKINS (J.D.) (eds), Small
animal pediatric medicine and surgery. 1st ed. ButterworthHeinemann Oxford, 1998, pp. 183-184.
LIGHTNER (B.A.), MCLOUGHLIN (M.A.), CHEW (D.J.), BEARDSLEY
(S.M.), MATTHEWS (H.K.), 2001: - Episioplasty for the treatment
of perivulvar dermatitis or recurrent urinary tract infections in
dogs with excessive perivulvar skin folds : 31 cases (1983-2000). J
Am Vet Med Assoc, 2001, 219:1577-1581.
MEYERS-WALLEN (V.N.), DONAHOE (P.K.), MANGANARO (T.),
PATTERSON (D.F.) - Müllerian inhibiting substance in sex-reversed
dogs. Biol Reprod, 1987, 37:1015-1022.
MEYERS-WALLEN (V.N.), PATTERSON (D.F.) - Disorders of sexual
development in the dog. In: Morrow DA (ed), Current therapy in
theriogenology. 2nd ed. WB Saunders Co Philadelphia, 1986, pp.
567-574.
NEUMANN (F.), ELGER (W.), STEINBECK (H.) - Drug-induced
intersexuallity in mammals. J Reprod Fertil suppl, 1969, 7:9-24.
NICKEL (R.F.) - Disorders of sexual differentiation. In: Rijnberk A (ed),
Clinical endocrinology of dogs and cats. 1st ed. Kluwer Academic
Publishers Dordrecht, 1996, pp. 157-163.
OLSON (P.N.), NETT (T.M.), BOWEN (R.A.), AMANN (R.P.), SAWYER
(H.R.), GORELL (T.A.), Niswender (G.D.), PICKETT (B.W.),
PHEMISTER (R.D.) - A need for sterilization, contraceptives,
and abortifacients : Abandoned and unwanted pets. Part II.
Contraceptives. Comp Contin Educ, 1986, 8:173-178.
ROTHUIZEN (J.), VOORHOUT (G.), OKKENS (A.C.), BIEWENGA (W.J.)
- Urovagina associated with female pseudohermaphroditism in four
bitches from one litter. Tijdschr Diergeneesk, 1978, 103:1109-1113.
SELDEN (J.R.), MOORHEAD (P.S.), KOO (G.C.), WACHTEL (S.S.),
HASKINS (M.F.), PATTERSON (D.F.) - Inherited XX sex reversal in
the cocker spaniel dog. Hum Genet, 1984, 67:62-69.
SHANE (B.S.), DUNN (H.O.), KENNEY (R.M.), HANSEL (W.), VISEK (W.J.)
- Methyl testosterone-induced female pseudohermaphroditism in
dogs. Biol Reprod, 1969, 1:41-48.
WENTINK (G.H.), BREEUWSMA (A.J.), GOEDEGEBUURE (S.A.), TEUNISSEN
(G.H.B.), AALFS (R.H.G.) - Drie gevallen van hermaphroditismus bij de
hond. Tijdschr Diergeneesk, 1973, 98:437-445.
Footnotes
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Oestradiol benzoate®, 0.01 mg/kg [0.0045 mg/lb], SC; Intervet, Mechelen, Belgium
Parlodel®, 10-20 μg/kg [4.5-9 μg/lb], PO, q 24h; Novartis Pharmaceuticals, Arnhem, The Netherlands
Durateston®, 2.5 ml, IM; Intervet, Mechelen, Belgium
Witness®, Synbiotics Corporation, Erembodegem, Belgium
GE Logiq 7, General Electrics Medical Systems, Milwaukee, USA
Dormicum®, Roche, Vilvoorde, Belgium
Mephenon®, Denolin, Brussels, Belgium
Hyperball Oral, Vygon, 5 mm ID, Ecouen, France
Isoflo®, Abboth, Queenborough, UK
Spiromat 656®, Dräger, Lübeck, Germany
Capnomac Ultima®, Datex, Helsinki, Finland; HP Omnicare CMSPatientenmonitor®, Hewlett-Packard GmbH, Böblingen, Germany
1 ml/ 4.5 kg[1 ml/ 10 lb]; Xylocaïne 2%®, Astra Pharmaceuticals, Brussels, Belgium
0.1 mg/kg [0.45 mg/lb]; Stellorphine sine conservans®, Stella, Liège,
Belgium
Vicryl® 2/0, Ethicon, Janssen Animal Health, Beerse, Belgium
Ethilon® 3/0, Ethicon, Janssen Animal Health, Beerse, Belgium
4% phosphate buffered formaldehyde solution
1/75 mouse monoclonal anti-human oestrogen receptor®, Dako, Glostrup, Denmark
1/300 mouse monoclonal anti-human progesterone receptor®,
Immunotech, Marseille, France
49
UROGENITAL SYSTEM
REPRINT PAPER (HILL’S)
Urinary tract infection –
a European perspective
B. Gerber(1)
INTRODUCTION
Urinary tract infection (UTI) refers to microbial colonization of any portion of the urinary system that is normally
sterile. The distal urethra is not sterile, but has a normal flora.[3] UTIs are usually caused by bacterial organisms that
are part of the microflora of the intestinal or the lower urogenital tract.[3] However, viruses and fungi may infect the
urinary tract.[4] UTI appears to be less common in cats than in dogs.
when the host’s defences are overwhelmed by microbes.[4]
Normal defences include wash-out of pathogens by normal
micturition with complete emptying of the bladder, an intact
mucosal layer with glycosaminoglycans, epithelial desquamation,
functional properties like ureteral peristalsis and local and
systemic immune competence. Furthermore urine itself has
antimicrobial properties that may play a role in limiting bacterial
growth including its high osmolality, and urine constituents with
antimicrobial effects (e.g., high concentrations of urea, organic
acids, Tamm-Horsfall mucoproteins or low-molecular weight
carbohydrates) and extreme values of urine pH.[19,25]
This paper is based on a lecture given at the Hill’s
European Symposium on Advances in Feline Medicine*
Prevalence
The prevalence of feline UTIs has not been defined, but has
been estimated to be in the range of 0.1 to one per cent, and
at least 10 times less than the estimated prevalence in dogs.[15]
It has been reported that one per cent of cats admitted to
veterinary teaching hospitals were diagnosed with UTI, and
in studies from the USA, the frequency of UTI as the cause of
lower urinary tract disease (LUTD) in cats ranged from 1 per cent
to 12 per cent.[1,6,12,14] In a recent two-year Swiss study of cats
with LUTD, UTI was found to be the underlying cause in 8 per
cent (FIGURE 1).[8] In another recent report from Norway the
proportion of cats with UTI was somewhat higher, accounting
for 18 per cent of the cats with LUTD.[16]
Organisms
Not all microbes are pathogenic. Bacteria need special virulent
factors to initiate a UTI. In Escherichia coli, adhesins are the
most firmly established virulent determinants, but typically there
is more than one virulent factor, including resistance to serum
bactericidal action, haemolytic activity, possession of certain O
and K-antigens, iron-scavenging proteins and bacteriocins.[25]
Escherichia coli and Staphylococcus spp. have been the most
common organisms isolated from UTIs in the studies reported
from cats. In one study, organisms responsible for feline UTIs
were bacteria in 28 per cent and viruses in 0.4 per cent, with
the causative agent not specified in the remainder.[14] Among
the bacteria, E. coli was found in 46 per cent of the cases,
Stapylococcus spp. in 9 per cent, Streptococcus spp. in 5 per
cent, Klebsiella spp. in 3 per cent, Proteus spp. in 3 per cent
and Pseudomonas spp. in 1 per cent. In 31 per cent the type
of bacteria was not designated. The viruses involved were not
Location And Host Defence
Infection can occur either in the upper or lower urinary tract
or at both sites simultaneously. However, it can sometimes be
difficult to detect the exact location of an infection.
Furthermore, an infection in one part of the urinary tract
increases the likelihood of another part of the urinary tract to
become infected as well.[3]
Involvement of the prostate in feline UTIs is rare.[23] Most UTIs
are the result of ascending migration of pathogens from the
distal urogenital tract to the sterile part, and the UTI develops
* Brussels 26-28th April 2006
(1) Clinic for Small Animal Internal Medicine, Vetsuisse Faculty University of Zurich, Winterthurstrasse 260 CH-8057 Zurich E-mail: bgerber@vetclinics.
unizh.ch
The lecture on which this paper is based was given at the 10th Annual Hill’s Symposium held in Brussels 26th -28th April 2006. Bernhard
Gerber is an Assistant Professsor for Small Animal Internal Medicine at the University of Zurich, Switzerland.
51
Urinary tract infection – a European perspective - B. Gerber
specified. Viruses have been considered as causative agents for
feline LUTD for a long time.[17] Recently two novel feline calici
viruses were isolated from urine of cats with naturally occurring
LUTD, although the causative relationship to LUTD remains
questionable.[22] In earlier studies, calici viruses, herpes viruses
and feline syncytiumforming virus have been isolated from urine
and tissues of cats with LUTD and suspected to be causative
agents in the aetiopathogenesis of LUTD.[13] Although not yet
proven, the viral hypothesis is supported by findings of virus-like
particles tentatively identified as calici viruses in a substantial
number of crystalline-matrix urethral plugs obtained from cats
with obstructive LUTD.[17] Fungal UTI in cats is often associated
with other forms of LUTD, and Candida spp. are the most
commonly reported organisms.[10,21]
Figure 2. Gender of cats with different types of LUTD.
(n = 77; 87 per cent of the cats were male.)
Signalment
Older cats (10 years+) have an increased risk of acquiring bacterial
UTI, while in cats less than one year old, the risk is minimal.[14]
Furthermore, cats with UTI have been shown to be significantly
older than cats with other forms of LUTD (i.e. five to 15 years,
median 13 years).[8] The proportional morbidity rate of UTI also
appears to increase with age,as reported by veterinary colleges
in the USA.[17] UTI has been more often identified as a cause
of LUTD in female cats than in male cats, and further analysis
revealed that female spayed cats had an increased risk of bacterial
UTI while female and male intact cats had a decreased risk.[14]
In another study, there were also significantly more female cats
in the group with UTI compared to other causes of LUTD such as
uroliths, urethral plugs and idiopathic LUTD (FIGURE 2).[8] It has
also been suggested that Abyssinian cats and overweight cats
have an increased risk of UTI.[7]
However, in a Swiss study, none of the cats with UTI as a causative
agent of LUTD were found to be overweight, while 12 per cent
of cats with uroliths,36 per cent of cats with idiopathic LUTD
and 50 per cent of cats with urethral plugs were overweight.[8]
Underlying conditions and
predispositions
Underlying conditions can increase the risk of UTI in cats. In a
study of diabetic cats, 10 per cent were reported to have UTI.
All of them had clinical signs of diabetes mellitus for more than
four weeks, and E. coli, Serratia spp. and a mixed population
of microbes were found.[11] After obstructive LUTD, indwelling
catheters with a closed system may be a cause of UTI.[2]
However, treatment is not advisable while the catheter is in
place, whereas urinalysis with culture and appropriate treatment
at the time of removal of the catheter is recommended.[2] UTI is
the most frequent late complication of perineal
urethrostomy.[5]
Clinical signs
Figure 1. Differential diagnosis of FLUTD – survey of 77 cats.
The clinical signs of cats with lower urinary tract disease are
relatively consistent regardless of the cause of the disease.[18]
They consist of haematuria, pollakiuria, stranguria and urination
in inappropriate places (also termed periuria) (TABLE 1). Urethral
obstruction may or may not be present (FIGURE 3). Only one study
has identified UTI as a primary cause of obstructive LUTD.[1] In
other studies of cats with and without obstructive LUTD, those
with UTI as the primary cause of the disease were not found to
be obstructed.[8,12] Gross haematuria as a historical feature has
been reported more frequently in cats diagnosed with UTI than
those with other causes of LUTD (TABLE 1).[8]
Diagnosis
The gold standard for diagnosis of UTI is urine culture. Examination
of the urine sediment provides some help in the identification
of UTI. More than four white blood cells per high power (x400)
field in sediment examined under a cover slip, together with
identification of bacteria, are indicative of UTI. However, the
presence of pyuria alone simply reflects any inflammatory cause
and is not synonymous with UTI. Equally, the absence of pyuria
52
Haematuria
Pollakiuria
Stranguria
Periuria
Pain
All cats
43
40
48
32
43
Cats with UTI
67
50
50
50
50
Table 1. Clinical signs in
77 cats with LUTD.
Per cent of cats showing
each of the clinical signs.
Therapy
does not rule out a UTI. Rod shaped bacteria might be seen
in the sediment if the concentration of bacteria in the urine is
greater than 10,000/ml, although cocci may not be seen until
the concentration reaches 100,000/ml. Care is needed though,
as the presence of bacteria might represent contamination or
amorphous particles resembling bacteria may be mistaken for
true bacteriuria.
Microscopic examination of modified Wright’s stained urine
samples has been shown to be superior to traditional wet
mounts when attempting to identify bacterial UTI in dogs. Urine
collected for culture should be obtained by cystocentesis. In
one study, while culture of urine was negative in 79 per cent of
cystocentesis samples, it was only negative in 55 per cent of the
same cats when collected by catheterization, and only negative
in 17 per cent when voided urine samples were cultured.[18]
Clipping and disinfection prior to cystocentesis have been shown
to be unnecessary.[24] The definition of significant bacteriuria in
cats seemingly involves lower numbers than in dogs when urine is
collected by catheterization or free catch, which is attributed to a
greater innate resistance of cats to UTI.[7,18,19] Proper handling
of the urine after collection is very important and urine should
ideally be cultured immediately after sampling because some
bacteria may multiply very rapidly while others may decrease
in number. Where immediate culture is not possible, boric
acid-containing tubes seem to be adequate for urine storage
at room temperature, at least in dogs, as culture results after
storage in a boric acid-glycerol-sodium formate tube for up to
48 hours at 20°C correlated well with the immediate culture of
the same urine.[20] Bacteriuria is considered significant (= UTI)
if there are more than 1,000 colony forming units per millilitre
of urine. Values below this or cultures with multiple types of
bacteria must be assessed carefully because both can indicate
contamination.
Administration of antimicrobial agents should be based on
susceptibility testing. Fortunately most antimicrobials are
present in urine in high concentrations as a result of renal
excretion, which means a good result can often be obtained in
an animal even if an antibiotic is used to which the organism is
reported to be resistant (because of the higher concentration in
the urine). An antimicrobial is said to be effective (the organism
is ‘sensitive’) if the urine concentration reaches four times the
minimum inhibitory concentration (MIC). Empirical treatment
is often necessary before culture and sensitivity results are
available. Antibiotics are chosen based on urine sediment results
(cocci or rods). Rods in acidic urine may represent E. coli while
in alkaline urine they may represent Proteus spp. Cocci in acidic
urine may represent Enterococcus spp. while in alkaline urine
Staphylococcus spp. is more likely. Appropriate antibiotics should
be given for two to three weeks in uncomplicated cases.[4]
Special caution is needed with the use of fluoroquinolones
because of the potential risk for retinal degeneration. As renal
impairment is often associated with UTI, it is speculated that
with decreased renal function fluoroquinolones may accumulate
which would require dosage reduction and monitoring for
mydriasis.[9,26]
Prognosis
Approximately 85 per cent of UTI in cats are single episodes and
do not recur.[15] Relapsing UTI might either be caused by the
same organism which was isolated before treatment (persistent
UTI) or by a different organism (recurrent UTI). In both cases a
further workup is required to identify the underlying causes. If
predisposing disorders are not addressed, control of UTI will be
poor. Reasons for poor response to therapy might be treatment
of a non-infectious problem with antibiotics, ineffectiveness
of the antibiotics because of inadequate delivery (poor client
compliance, poor patient acceptance, ineffective drug or
impaired drug transport), resistant microbes or superinfection
with another organism. For example, super infections can
occur when antimicrobials are given while a urinary catheter is
in place. Prophylactic antimicrobial therapy might be indicated
after catheterization. Long-term lower dose therapy might
be indicated if the patient experiences relapses each time
antimicrobial therapy is stopped. This treatment strategy is not
well studied in veterinary medicine. It has been suggested that
half to a third of the usual therapeutic dose of an antimicrobial
is given every evening for this purpose.[4] The choice of the
antimicrobial is based on the last positive culture and the
duration of therapy is at least six months. If adopting this
approach, urinalysis and culture should be performed every four
to eight weeks.
Figure 3. Presence of obstruction in cats with different types of
LUTD.
53
Urinary tract infection – a European perspective - B. Gerber
References
[1]
BARSANTI (J.A.), BROWN (J.), MARKS (A.), et al. Relationship
of lower urinary tract signs to seropositivity for feline
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[2] BARSANTI (J.A.), SHOTTS (E.B.), CROWELL (W.A.), et al. - Effect
of therapy on susceptibility to urinary tract infection in male cats
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[3] BARSANTI (J.A.) - Genitourinary Infections. In: Infectious diseases
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[4] BARTGES (J.W.) - Urinary tract infections. In: Textbook of
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[5] BASS (M.), HOWARD (J.), GERBER (B.), MESSMER (M.)
- Retrospective study of indications for and outcome of perineal
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[6] BUFFINGTON (C.A.T.), CHEW (D.J.), KENDALL (M.S.), et al.
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[7] FRY (D.R.), HOLLOWAY (S.A.) - Comparison of normal urine
samples collected by cystocentesis with and without prior skin
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[8] GERBER (B.),BORETTI (F.S.),KLEY (S.),et al. - Evaluation of clinical
signs and causes of lower urinary tract disease in a population of
European cats. J Small Anim Pract, 2005, 46: 571-577.
[9] HOSTUTLER (R.A.),CHEW (D.J.),DIBARTOLA (S.P.) - Recent
concepts in feline lower urinary tract disease. Vet Clin North Am
- Small Anim Pract 2005, 35 (1): 147-170.
[10] JIN (Y.),LIN (D.) - Fungal urinary tract infections in the dog and
cat: A retrospective study (2001-2004). J Am Anim Hosp Assoc,
2005, 41: 373-381.
[11] KIRSCH (M.) - Incidence of bacterial cystitis in recently diagnosed
diabetic dogs and cats. Retrospective study 1990–1996. Tierärztl
Prax, 1998, 26: 32-36.
[12] KRUGER (J.M.), OSBORNE (C.A.), GOYAL (S.M.), et al. - Clinical
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[13] KRUGER (J.M.), OSBORNE (C.A.) - The role of uropathogens in
feline lower urinary tract disease. Clinical implications. Vet Clin
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[14] LEKCHAROENSUK C, OSBORNE CA, LULICH JP. - Epidemiologic
study of risk factors for lower urinary tract diseases in cats. J Am
Vet Med Assoc, 2001, 218: 1429-1435.
[15] LING (G.V.) - Bacterial infections of the urinary tract. In:Textbook
of Veterinary Internal Medicine. Ettinger S.J., Feldman E.C., edits
WB Saunders Company, Philadelphia, 2000: 1678-1686.
[16. LUND (H.S.), KRONTEVIT (R.), SORUM (H.), EGGERTSDOTTIR (A.V.)
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[17] OSBORNE (C.A.), KRUGER (J.M.), LULICH (J.P.), POLZIN (D.J.),
LEKCHAROENSUK (C.) - Feline lower urinary tract disease. In:
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[18] OSBORNE (C.A.),KRUGER (J.M.),LULICH (J.P.) - Feline lower
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Baltimore., 1995, 757-797.
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[24]
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EX0TICS AND CHILDREN’S PETS
COMMISSIONED PAPER
Rabbit dentistry
A. Meredith(1)
SUMMARY
Dental disease is one of the most common reasons for presentation of a rabbit to the veterinary surgeon, although
this fact may not be immediately apparent. Anorexia, weight loss, facial swelling, ocular discharge, lack of grooming,
accumulation of caecotrophs and fly strike should all alert the practitioner to the possibility of dental disease, and a
full dental examination should be carried out. Even in rabbits with no apparent clinical signs, assessment of the teeth
should always be an essential part of the clinical examination, as early detection and treatment of disease is more
likely to have a good outcome. Unfortunately, many rabbits are presented with later stages of disease, where cure is
not possible and palliative treatment is all that is achievable. The majority of cases of dental disease are preventable
by the feeding of a natural high fibre diet, and thus owner education is vital.
much of the crown is subgingival. Some refer to the visible oral
portion as the clinical crown. Because of the continued eruption
of rabbit teeth, the periodontal ligament has finer collagen fibrils
and is relatively weak.
This paper was commissioned by
FECAVA for publication in EJCAP.
Dental Anatomy and Physiology
The first incisor teeth have a chisel-like occlusal surface (Fig 1). The
thicker layer of labial enamel means that the lingual side wears
more quickly, forming the chisel shape of the cutting surface.
At rest the tips of the mandibular incisors fit between the first
and second maxillary incisors. Functionally the incisor teeth are
used with a largely vertical scissor-like slicing action to cut food.
During incisor use the cheek teeth are out of occlusion. Incisor
wear, growth and eruption are balanced in a normal rabbit at a
rate of about 3mm per week.
The dental formula of the rabbit is: 2 x ( I 2 / 1 C 0 / 0 P 3 / 2 M
3 / 3). Rabbits do have a deciduous dentition, but this is of no
clinical significance as it is shed within the first few days after
birth.
Rabbits have six unpigmented incisor teeth. There are four
maxillary incisors, two labially, which have a single vertical
groove in the midline, and two rudimentary “peg teeth” located
palatally. There is a large diastema between the incisor and
premolar teeth. The premolar teeth are similar in form to the
molar teeth, and are usually described together as the ‘cheek
teeth’. They are closely apposed and form a single functional
occlusal grinding surface. The premolars and molars have a
groove on the buccal surface formed by infolding of enamel.
Slower wear of the enamel at the circumference of the teeth
and the infolding compared to the softer dentine creates ridges,
which are matched by depressions in the opposite tooth, and
increase grinding efficiency. It should be noted that normal
rabbits frequently have a small vertical ridge along the lingual
surface of the cheek teeth – this should not be confused for
abnormal “spikes” which are always lateral (see below).
Cut food is prehended by the lips and passed to the back of the
mouth for grinding. Food is ground by the cheek teeth with a
wide lateral chewing action, concentrating on one side at a time.
The mandible is narrower than the maxilla, and the cheek teeth
are brought into occlusion by lateral mandibular movement. The
mandible is moved caudally to allow chewing, and the incisors
are separated during this phase.
The natural rabbit diet of grasses and other leafy plants is highly
abrasive as it has a high content of silicate phytoliths, so there is
normally rapid wear of the cheek teeth, around 3mm per month
in a wild rabbit, balanced by equally rapid tooth growth and
eruption. Mandibular incisors and cheek teeth grow and erupt
faster than maxillary teeth.
All teeth erupt continuously and do not have a true anatomical
roots (aradicular (= without a root) hypsodont (=high crowned)).
Roots are more correctly described as “reserve crowns”, thus
Maxillary and mandibular bone growth, development and
maintenance is also dependent on the mechanical stresses to
(1)Anna Meredith MA VetMB CertLAS DZooMed MRCVS RCVS Recognised Specialist in Zoo and Wildlife Medicine Head of Exotic Animal Service
University of Edinburgh Royal (Dick) School of Veterinary Studies Easter Bush Veterinary Centre Midloathian GB- EH25 9RG
E-mail:[email protected]
55
Rabbit dentistry - A. Meredith
– Anorexia
– Weight loss
– Facial swellings/asymmetry
– Ocular discharge
– Lack of grooming
– Accumulation of caecotrophs
– Fly strike (myiasis)
Any of these should all alert the practitioner to the possibility of
dental disease, and a full dental examination should be carried
out. Even in rabbits with no apparent clinical signs, assessment
of the teeth should always be an essential part of the clinical
examination, with as detailed an examination as is possible in a
conscious animal being performed.
Clinical examination
A dental examination should be preceded by a full history,
including a detailed dietary history. Clinical examination should
include:
– Facial palpation – for any bony or soft tissue swellings,
especially palpation of the ventral border of the mandible
where elongated apices may be present.
– Assessment of degree of lateral movement of the mandible
– Examination of length, quality and occlusion of the incisors
– Examination of the cheek teeth
1. Normal incisors, demonstrating the chisel-shaped occlusal
surface
which it is subjected. Rabbits which do not spend prolonged
periods chewing typically show poor jaw bone development,
or atrophy, at muscle insertions. This is most prominent in the
area of insertion of the pterygoid (medial) and masseter (lateral)
muscles into the ramus; the bone in this area may be so thin that
it is transparent or there may even be a perforation where the
bone has atrophied completely.
An initial examination of the cheek teeth can be carried out
in the conscious animal, with use of an otoscope, although it
must be recognised that visibility and detection of abnormalities
will be limited. It is estimated that conscious examination will
reveal only 50% of abnormalities, however. If dental disease is
suspected or lesions are detected in the conscious examination,
examination under deep sedation or anaesthesia must be
performed. This requires the use of specialist gags and cheek
retractors to enable good visualisation (Fig 3). Even then, it is
estimated that only 75% of lesions will be detected, with the
remainder only being picked up on post-mortem examination
(D A Crossley personal communication).
The nasolacrimal duct of the rabbit passes close to the apex of
the maxillary incisors and the first maxillary premolar. (Fig 2)
Clinical signs of dental disease
Dental disease is one of the most common reasons for presentation
of a rabbit to the veterinary surgeon, although this fact may not
be immediately apparent. The commonest signs are:
2. Contrast radiography of the nasolacrimal duct, lateral and DV views
56
4. Normal lateral skull radiograph
3. a) Visualisation of the cheek teeth requires anaesthesia and the use of incisor gags and cheek pouch retractors. (Picture courtesy D.A
Crossley) b) A table top gag is also commercially available for this purpose, and allows single-handed oral inspection
Radiography
Abnormalities of the reserve crown and apex can only be
assessed radiographically, and radiography is an essential part of
a complete dental examination, enabling a full diagnosis, staging
and a judgement of prognosis [17]. Computed tomography (CT)
is also a very useful diagnostic tool, especially for assessment of
dental-associated abscesses, and is being used more widely.
teeth leads to this being lost and the palatine bone and ventral
border of the mandible becoming parallel or even slightly
divergent. There is some breed variation, however.
– Shape of occlusal surfaces – incisors should be chisel-shaped,
cheek teeth should show an even zigzag pattern, even when
superimposed on the lateral view. Waves or steps may be
detected.
– Alveolar bone quality. There should be a fine lucent line
between the alveolar bone and the subgingival crown. If this
is blurred it can indicate ankylosis. Areas of increased bone
lucency may indicate infection or abscessation
Standard views are dorsoventral and lateral, plus a rostrocaudal
view is also useful. After assessment of these, oblique views may
be necessary to separate superimposed areas of interest.
Dental disease
When interpreting radiographs, possession of radiographs of
a normal animal ( Fig 4), and a normal prepared skull, can be
very useful. However, it should be recognised that there is a
great variety in shape and structure of rabbit skulls depending
on breed. The main points to assess are:
Tooth elongation – eruption rate exceeding wear rate
This is the probably the commonest cause of dental disease in pet
rabbits and presents as a progressive pattern of abnormalities.
Rabbits on a low fibre and high carbohydrate diet have reduced
tooth wear or attrition, resulting in elongation of the crown.
It is noticeable that rabbits consuming a low fibre mixed grain
or pelleted diet tend to crush these items with an “up and
down” motion rather than the lateral grinding motion employed
when eating a highly fibrous diet. Deficiency of calcium and
vitamin D as a result of selective feeding and lack of exposure
to sunlight respectively, have also been proposed as causative
or exacerbating factors, [9,12] although opinions vary on the
significance of these.
Elongation causes occlusion of the cheek teeth at rest, resulting
in increased intrusive pressure. As elongation continues, the
mandible and maxilla are forced apart (seen radiographically as
the palatine shadow and ventral border of the mandible becoming
more parallel [13] and the masseter muscles stretched, which
also results in increased intrusive pressure. The teeth start to
intrude (apices become palpable as bony mandibular swellings)
and the crowns tip and/or rotate. Clinically, slight elongation of
the supragingival crown is difficult to appreciate, but it is more
obvious radiographically. As elongation and disrupted eruption
continue the altered forces and reduction in lateral movement
during chewing lead to the formation of ‘spurs’ on the lingual
occlusal surface of the mandibular cheek teeth and the buccal
– Clinical (supragingival) crown length
– Position of the apices (elongation/intrusion)
– Degree of rostral convergence of the palatine bone and the
ventral border of the mandible. In a normal animal there is
generally some convergence, while elongation of the cheek
5. A large lingual spur is visible on the left mandibular premolar
in this rabbit (Picture courtesy D.A Crossley)
57
6. a) Wild rabbit mandible, showing short cheek teeth. b) A domestic rabbit mandible, demonstrating elongation of the cheek teeth. (Picture
courtesy D.A Crossley)
surface of the maxillary cheek teeth (Fig 5). Spurs or spikes, even
as small as 0.1mm, are always significant and indicate a relatively
advanced stage of disease, and can cause great discomfort and
pain.
The exact pattern of disease progression varies amongst
individuals and depends on the degree of elongation and
dysplasia. In many rabbits severe dysplasia may eventually result
in complete cessation of growth due to ankylosis and resorption
of the teeth (see below), which, perhaps paradoxically, can
improve or even resolve the associated clinical signs.
Elongation of the cheek teeth prevents the mouth from closing
fully (Fig 6). This separates the incisor teeth reducing their wear
until they have elongated sufficiently to compensate. Beyond
a certain level of elongation the incisors no longer function
adequately and occlusal wear abnormalities become apparent,
i.e. a secondary incisor malocclusion and elongation occurs (Fig
7). Thus any rabbit presenting as an adult (>3-4 months) with
incisor problems should always be checked for cheek tooth
disease.
Jaw length abnormalities
Primary incisor malocclusion and overgrowth is seen with
mandibular prognathism/maxillary brachygnathism in some
dwarf and lop breeds (Fig 8). In these cases the problem can be
detected at a very early age. It is common for the mandibular
incisors to become straighter preventing any correction of the
problem in mild cases. The maxillary incisors are not worn, but
contact with the mandible maintains occlusal pressure so the
tight spiral curvature of growth continues, the teeth eventually
penetrating the palate or cheek if left untreated. Regular crown
reduction or, preferably incisor extraction, is indicated for
affected animals.
Elongation of the maxillary cheek teeth can impinge on the
nasolacrimal duct and cause bony distortion and blockage,
resulting in ocular discharge, with or without associated
infection. Elongation of the maxillary incisors can have the same
effect on the duct more rostrally. Contrast radiography of the
nasolacrimal duct is a useful technique (See Fig 2).
Traumatic injury
Separation of the mandibular symphysis is the most common
accidental injury. Pulp exposure may occur associated with
7. Lateral skull radiograph showing marked cheek tooth elongation
and a secondary (acquired) incisor malocclusion (Picture courtesy
D.A Crossley)
8. Primary incisor malocclusion
58
9. Pus present at the mandibular incisors, which have stopped
growing, as a result of pulpitis and abscessation subsequent to
repeated trimming with nail clippers
10. Prepared skull showing extensive bony distortion associated
with mandibular and maxillary tooth root abscessation (Picture
courtesy D.A Crossley)
Prevention and treatment of dental
disease
both dental fractures and trimming by a veterinary surgeon.
If the exposure is small and the blood supply to the pulp is
undamaged it may heal unaided, but many cases require partial
vital pulpectomy and vital pulp therapy, a specialist procedure.
In untreated cases pulpitis and pulp necrosis are common, with
the formation of abscesses around the premolar tooth roots
days to months later (Fig 9).
If rabbits are fed on fresh and dried grasses and other herbage,
dental disease is generally rare. Unfortunately the incidence in
some, particularly extreme dwarf and lop breeds, approaches
100% whatever their diet.
Periodontal disease and facial abscesses
Coronal reduction
Periodontal disease is common in rabbits, especially as the weak
structure of periodontal ligament renders it more likely to injury
and food impaction Elongation is a significant factor, especially
with the cheek teeth, as this causes disruption of the tightly
packed occlusal surface and the opening up of gaps (diastemas)
between the teeth. Periodontal infection, often with anaerobic
oral bacteria such as Fusobacterium species, or Staphylococcus.
or Streptococus spp. [16] may spread to the tooth apex, leading
to endodontic lesions as the infection affects the pulp. Abscesses
frequently result from periodontal infection, or mucosal damage
caused by dental ‘spikes’. Unfortunately most dental abscesses
result in gross changes in the surrounding tissues including the
alveolar bone, so that there are residual problems even if the
abscess is successfully treated. If not treated early, abscesses
tend to behave as expansile masses, and they can displace teeth
(Fig 10).
When detected in its very earliest stages, uncomplicated tooth
elongation can be corrected simply by dietary change. Established
tooth overgrowth may be helped by repeating burring at 4 to
6 week intervals. Radiographic assessment of tooth roots is
essential in all cases before undertaking treatment.
Incisors
In the unlikely event that problems are restricted to the incisor
teeth then these can easily be trimmed back to a normal length
and shape, or if repeated treatment is needed they can be
extracted. Incisor trimming can be performed without difficulty
in conscious animals using either high or low speed dental
equipment. A high speed handpiece rotating at 2-400,000
times a second will cut the teeth with minimal effort, but care
should be taken to avoid overheating. Low speed burrs can also
be used but they are less efficient, and should only be applied
for a maximum of 5 seconds before removal to allow cooling.
Diamond discs are hazardous and not recommended. Taper
fissure burrs are most efficient with either high or low speed
handpieces, and soft tissues should be protected, e. g by placing
a wooden tongue depressor behind the incisors. The aim is to
restore normal crown height and the chisel shape. Care should
be taken not to expose the pulp. In the normal incisor pulp is
unlikely to extend more than 3mm above the gingival, but this
may be much more ( up to 17mm maxillary, 27mm mandibular)
in the overgrown incisor [6]. If exposed, vital pulp therapy using
calcium hydroxide cement is required, generally a specialist
procedure. Clippers should never be used as they leave sharp
edges and longitudinal cracks in the teeth and will often expose
the pulp. Clipping also releases a considerable amount of energy
Dental caries and resorption
High carbohydrate diets, reduced attrition and arrested eruption
predispose to caries (demineralisation), which can totally destroy
the exposed crown and progress subgingivally stimulating
resorption. Resorptive lesions are also seen associated with
periodontal disease and abscesses. If affected animals survive
long enough, replacement resorption may eventually result in
the disappearance of most of the cheek teeth. Affected rabbits
often do well on a suitably processed diet, though there are
continuing problems with progressive eruption remaining nonoccluding teeth.
59
11. An example of a low speed dental machine and handpiece
12. Coronal reduction of cheek teeth using a low speed handpiece with
taper fissure burr and protector (Picture courtesy D.A Crossley)
into the tooth, concussing the pulp, and damaging the highly
innervated periodontal and periapical tissues, causing pain.
differential wear. It also may take some time for the jaw muscles
to recover their ability to contract fully after radical coronal
reduction. Repeated treatments, initially at 4-6 week intervals,
are generally necessary, but these intervals will generally increase
as the pattern of cheek tooth eruption becomes apparent
Cheek teeth
Coronal reduction of cheek teeth requires general anaesthesia,
and specialist mouth gags and cheek dilators. A straight slow
speed dental handpiece (Fig 11) with a long-shanked taper
fissure burr is recommended. A burr protector may be used (Fig
12). Avoidance of soft tissue trauma is vital, but can be difficult
due to the limited space and visualisation. Moistening the teeth
with a damp cotton bud can help prevent the burr “walking
off” the tooth. Hand held molar clippers may be used initially
to remove large spikes. There is little point in simply removing
sharp edges or ‘spikes’ as the main problem, tooth elongation,
is not then addressed. Hand held rasps are often too coarse and
not favoured by the author, as the forces applied can lead to
tearing the periodontal ligament and loosening teeth. However,
if powered equipment is not available, molar clippers (Fig 13)
and fine diamond rasps may be used.
Early caries may be eliminated by burring away the affected
tissue. However, they often re-form unless the diet is corrected
and the coronal reduction may result in abnormal wear of
opposing teeth. Periodontal pockets deeper than 3mm are
difficult to clean in rabbits. Standard subgingival curettes may
be used but small dental excavators are often more effective.
Deeper pocketing is usually associated with abscessation in
which case the tooth will need extracting. This will also result in
abnormal wear of opposing teeth.
Extraction of teeth
Principles of extraction in rabbits are the same as for removal of
brachydont teeth in cats and dogs, i.e:
– Assessment
– Treatment planning
– Anaesthesia
– Cleansing of the operative field
– Incision of the gingival attachment
– Severance of the periodontal ligament
– Enlargement of the alveolus
– Removal of supporting alveolar bone if necessary
– Gentle lifting of the detached tooth from its socket
– Encouragement of formation of a stable alveolar blood clot
The aim of coronal reduction is to shorten the crown and
attempt to restore the normal occlusal pattern. The stage of
disease will influence the treatment – in the early stages where
apical changes are minimal, restoration of normal anatomy and
function may be possible, but unfortunately this is seldom the
case as rabbits are not presented until the disease has reached a
later stage. In later stages, where changes in tooth morphology
are extensive, burring is palliative only, to remove painful spikes
and spurs and reduce crown height. Where changes are very
severe and eruption has ceased due to ankylosis or major damage
to the periapical tissues, coronal reduction is not indicated as
the teeth cannot grow again to restore occlusion and chewing
ability will be removed. In summary, coronal reduction is
advocated until eruption has ceased. Coronal reduction takes
teeth out of occlusion, removing intrusive pressure, so allowing
teeth to erupt as normally as possible. Radical reduction may
expose sensitive dentine and cause discomfort. Burring removes
the transverse occlusal ridging so chewing efficiency is greatly
reduced until occlusion is resumed and ridging re-forms through
Analgesia must be provided in the post-operative period. The
rabbit should be bright, alert and eating within 2-4 hours
postoperatively following appropriate anaesthesia and analgesia.
If substantial soft tissue or bone trauma was present (or created
iatrogenically) then a nasogastric tube may be used for nutritional
supplementation until the rabbit is able to eat normally. The
animal should be weighed daily in the post-operative period to
ensure weight loss does not occur. Food items must be prepared
in bite sized particles; vegetables may be chopped or grated. If
60
cause for extraction is in association with facial abscess
treatment (see below). Some abnormal cheek teeth may be
extracted per os by simple traction if the periodontal ligament
is weak or root pathology is such that the tooth is loose. The
curvature of the tooth should be taken into account when
attempting to extract the tooth. If the periodontal ligament is
still intact, it may be broken down using a modified elevator
and the tooth extracted orally (see Fig 13 for molar elevator/
luxator and extraction forceps). The small size of the oral cavity
relative to the instrument makes intra-oral manipulation of the
tooth difficult. Once loosened the tooth should be intruded
into its alveolus and manipulated to help destroy any remaining
germinal tissue prior to removal. The pulp should remain in the
extracted tooth. If not, the germinal tissues are probably intact
and should be actively curetted using a sterile instrument. If the
germinal tissues are left intact the tooth will regrow, possibly as
a normal tooth, but more likely with gross deformity, in some
cases forming a pseudo-odontoma within the jaw bone.
13. Dental equipment available for rabbits. From left to right: molar
cutters, Crossley molar elevator/luxator, molar extraction forceps,
incisor gag, cheek dilators, Crossley incisor elevator/luxator, rasp (d)
Ankylosis of the tooth makes extraction very difficult and
an open technique is required. The removal of a molar via a
buccotomy incision, removal of alveolar bone and replacement
of a gingival flap requires careful technique and intensive postoperative care to ensure a successful recovery.
the animal does not eat voluntarily within 4 hours, nutritional
and fluid support must be instigated. The normal rabbit uses the
incisors for grooming, so if these have been removed the rabbit
should be groomed regularly to prevent matting of the coat.
Incisor removal
Radiography is required before incisor removal to establish any
associated pathology and molar involvement [2]. The gingival
attachment around the incisor is cut using a hypodermic needle
or a no 11 scalpel blade. An incisor elevator/luxator (See Fig 13)
(or blunted hypodermic needle) is then inserted along the mesial
aspect of the tooth to break down the periodontal ligament. The
elevator should follow the line of the tooth taking into account
its natural curvature. Gentle but sustained pressure is exerted on
the mesial and distal aspect of the tooth until it is loosened – it
is generally not necessary to luxate the ligament on the buccal
or lingual/palatal surfaces as it is so weak here. Once loosened,
the tooth should be gently rotated and pressed back into the
socket to destroy apical germinal tissue – failure to do this will
result in tooth regrowth, and even when this is done incisors will
occasionally regrow [14]. Alternatively, the apical tissue may be
debrided with a small curette after extraction of the tooth. The
tooth is then extracted using gentle traction. Excessive traction
may result in fracture of the teeth especially if they are of poor
quality. All 6 incisors should be removed; the small incisors (peg
teeth) require minimal luxation. The alveolus may be packed
with an anticoagulant sponge to limit haemorrhage in the post
operative period. The gingiva may be left to heal by granulation,
or closed with fine (5/0) absorbable suture material. If a tooth
breaks, the rabbit can be re-presented a few weeks later when
the crowns have re-erupted for completion of the extraction. If
the periapical tissues have been damaged, regrowth may not
occur and surgery may be required to retrieve the stump before
it serves as a nidus for infection or progresses to tooth root
abscessation.
It should be remembered that each molar opposes with two
others. These teeth may need corrective trimming following
extraction of one opposing tooth and so the rabbit should be
checked regularly.
Treatment of dental abscesses
The three main components of successful dental abscess
treatment are:
– Surgical removal/debridement of the abscess and any
associated teeth and infected bone
– Local antibiosis
– Systemic antibiosis
Surgical removal should be extracapsular where possible and
all associated teeth and infected bone must be removed. A
common reason for recurrence of abscesses, in the author’s
opinion, is failure to perform sufficiently aggressive surgery.
Radiography is an essential part of the pre-surgical assessment,
in order to identify which tooth/teeth are involved and the
extent of involvement of the surrounding tissues.
Local antibiosis may be achieved in several ways. Installation
of antibiotic-impregnated polymethylmethacrylate (AIPMMA)
beads into the defect created by surgical removal is a common
technique that allows locally high antibiotic levels with little
systemic absorption [1,15]. Systemic antibiotics are given for
2-3 weeks post-operatively. The choice of antibiotic should
preferably be based on culture and sensitivity results. PMMA
with gentamicin already incorporated may be purchased
directly (e.g Refobacin® Bone Cement R (a)). Pre-made beads
are available (e.g Septopal® (b)) but these are often too large
for use in rabbits. AIPMMA beads are rapidly encapsulated by
Cheek tooth extraction
Cheek tooth extraction can be very difficult unless the tooth
is already loosened by periodontal disease. The most common
61
fibrous tissue, after which only tissues up to 3mm away receive
the high concentrations of antibiotic. Thus placing them within
the abscess capsule will be ineffective. The author and others
(David Crossley personal communication) have had good success
filling the surgically-created defect with doxycycline gel (e.g
Atridox® (c)). This is also useful for packing defects secondary to
periapical infection. Both these techniques involve closure of the
wound, enclosing the implant. AIPMMA beads do not generally
need to be removed, as they are biologically inert. Packing the
cavity with calcium hydroxide is favoured by some but has been
reported to cause serious tissue damage and necrosis [1].
[8]
[9]
[10]
[11]
[12]
[13]
An alternative technique of achieving local antibiosis is to
marsupialise the surgical cavity and allow it to heal by granulation,
while flushing with or instilling antibacterial/antibiotic solutions.
This technique has the advantage of allowing more control
over continued treatment of the site and easier monitoring and
detection of recurrence.
[14]
[15]
[16]
Systemic antibiosis is generally not necessary for more than 2-3
weeks post-operatively in case surgery causes a bacteraemia.
However, in cases where complete excision is not possible,
long term systemic antibiosis may be necessary. Long term use
of antibiotics that have good efficacy against the anaerobic
organisms involved with dental abscesses, such as penicillin
G (by subcutaneous injection, never orally) are anecdotally
reported to have good success in preventing progression of
abscesses, or helping to achieve a cure when combined with
surgical debridement.
(a) Biomet Cementing Technologies AB, Forskaregatan 1, SE-275
37Sjöbo,Sweden www.bonecement.com
(b) BioMet Europe, Dordrecht, Netherlands
(c) CollaGenex Pharmaceuticals Inc. 41 University Drive, Suite 200
Newtown, PA 18940
(d) Veterinary Instrumentation Limited, Broadfield Road, Sheffield, S8
OXL United Kingdom. www.vetinst.com
References and further reading
Note: The following references are not referred to in the text and are
intended as suggested futher reading. 3, 4, 5, 7, 8, 10, 11, 18
[1] BENNETT (R.A.) - Managing abscesses of the head. BSAVA
Congress Scientific Proceedings, 2001, 15-16
[2] BROWN (S.A.) - Surgical removal of incisors in the rabbit. Journal
of Small Animal Exotic Medicine, 1992, 1(4):150-153
[3 CROSSLEY (D.A.) - Clinical aspects of lagomorph dental anatomy:
the rabbit (Orytolagus cuniculus). J Vet Dent, 1995, 12(4):137140.
[4] CROSSLEY (D.A.) - Prevention and treatment of dental problems
in pet rabbits and rodents. Proceedings of DVG, Hanover, August
1997.
[5] CROSSLEY (D.A.) Dental disease in lagomorphs and rodents.
In: Kirk’s Current Veterinary Therapy XIII, ed. Bonagura JD. WB
Saunders, Philadelphia, 2000, 1133-1137.
[6] CROSSLEY (D.A.) - Risk of pulp exposure when trimming rabbit
incisor teeth. Proceedings of the 10th European Veterinary Dental
Society Annual Congress, Berlin, 2001, 175-196.
[7] GORREL (C.) - Dental diseases in lagomorphs and rodents. In:
Veterinary Dentistry for the General Practitioner, Saunders,
London, 2004, 175-196.
[17]
[18]
HARCOURT-BROWN (F.M.) - A review of clinical conditions in
pet rabbits associated with their teeth. Veterinary Record, 1995,
137:341-346.
HARCOURT-BROWN (F.M.) - Calcium deficiency, diet and dental
disease in pet rabbits. Veterinary Record 1996, 139: 567-571.
HARCOURT-BROWN (F.M.) - Diagnosis, treatment and prognosis
of dental disease in pet rabbits. In Practice, 1997, 19:407-421.
HARCOURT-BROWN (F.M.) - Dental diseases. In :Textbook of
Rabbit Medicine, Butterworth Heinemann, 2002, 165-205.
HARCOURT-BROWN (F.M.), BAKER (S.J.) - Parathyroid hormone,
haematological and biochemical parameters in relation to dental
disease and husbandry in rabbits. JSAP, 2001, 42(3):130-136
HOBSON (P.) - Dentistry. In : Manual of Rabbit Medicine and
Surgery, BSAVA Publications, 2006, 184-196.
STEENKAMP (G.), CROSSLEY (D.A.) - Incisor tooth regrowth in
a rabbit following complete extraction. Veterinary Record, 1999,
145: 585-586.
TOBIAS (K.M.), SCHNEIDER (R.K.), BESSER (T.E.) - Use of
antimicrobial-impregnated polymethylmethacrylate. JAVMA,
1996, 208: 841-844
TYRRELL (K.L.), CITRON (D.M.), JRENKINS (J.R.), GOLDSTEIN
(E.J.) - Periodontal bacteria in rabbit mandibular and maxillary
abscesses. J Clin Micro, 2002, 40:1044-1047.
VERSTRAETE (F.J.M.), CROSSLEY (D.A.), HORNOF (W.J.) Diagnostic imaging of dental disease in rabbits. Proceedings of
18th Annual Veterinary Dental Forum, Fort worth, Texas, 2004.
WIGGS (R.), LOBPRISE (H.) - Dental and oral disease in rodents
and lagomorphs. In : Veterinary Dentistry – Principles and Practice,
Lippincott-Raven, Philadelphia, 1997, 518-537.
The FECAVA Symposium 2006*
Healthy dog breeding
L→R: Ellen Bjerkås, Astrid Indrebø, Sofia Malm, Ottmar Distl
INTRODUCTION
The 2006 FECAVA Symposium took place during the CSAVA/FECAVA/WSAVA Congress in Prague in October. FECAVA,
being an association concerned both about the companion animal profession and the well-being of the animals in our care, is
naturally also concerned about matters related to breeding and health. However, FECAVA’s task is not to re-invent the wheel,
but more to collate and disseminate information from bodies already involved in this work. The idea of FECAVA symposia
is to bring together scientists working in the same field but with a different approach to the same topic. Two years ago, in
Rhodes, the title of the FECAVA Symposium was “How can we take care of health, welfare and diversity of breeds”? This
year’s symposium might be considered a continuation of the questions raised in Rhodes.
A brief survey on existing national breeding programmes showed that there is great variation in what is registered, how
the results are registered and the possible consequences the results of screening programmes have for breeding advice.
In addition, screening programmes have only been established for disease groups where diagnosis can be established
relatively easy. However, we all know that there are a series of hereditary diseases that may be detrimental to the
animal, but which are at present not taken into consideration in most breeding programmes. Examples of this are skin
diseases, cardiac diseases and other skeletal diseases than hip and elbow dysplasias.
The lecturers at the 2006 symposium were Astrid Indrebø, PhD, veterinary scientific director of the Norwegian Kennel
Club, Sofia Malm DVM, Swedish University of Agricultural Sciences / The Swedish Kennel Club, and Prof. Dr. Ottmar
Distl, Tierärztliche Hochschule Hannover.
A synopsis of these presentations follows this introduction.
Ellen Bjerkås, President FECAVA
*Held during the 12th FECAVA/30th WSAVA/CSAVA Congress in Prague October 2006
63
The value of breeding programmes
A. Indrebo dvm PhD Veterinary Scientific Director, Norwegian Kennel Club, Norwegian School of Veterinary Science, Department of
Companion Animal Clinical Science, PO Box 8146 Dep., N-0033 Oslo, E-mail: [email protected])
INTRODUCTION
The last 10-15 years have seen major developments in veterinary science, giving us the knowledge, equipment and
medicine to diagnose and treat a large number of diseases. The fact that more dogs are diagnosed and treated, can
give the impression that dogs are more diseased now than they were a decade ago. Has all our effort in regulating
breeding through screening, breeding programmes and advice failed? Because advanced treatment allows even
diseased dogs to live a longer and happier life, maybe breeding programmes are less important than they used to be?
On the other hand, advanced possibility for diagnosis should give us a great tool in preventing hereditary diseases
and diseases with genetic disposition that are provoked by the environment. This can partly be done through
screening programmes, but they have obvious limitations. Screening programmes are available only for a small
number of diseases, and these are not necessarily the most important diseases for the dogs’ functional health. And for
diseases like hip dysplasia (HD) and elbow dysplasia (ED), where the environment plays a major role in forming the
dogs’ phenotype, the screening result of a dog does not necessarily tell the truth about the dogs’ genotype. Studies of
various populations and breeds show heritability estimates ranging from 0.1-0.6 for HD [1-7], and 0.1-0.4 for ED [6, 811]. Selection and combination of dogs based on breeding values, will hopefully be a valuable indicator for the future
breeding programmes on polygenetic diseases, as a breeding value is based not only on the screening result of the
dog and his offspring, but also on a large number of ancestors and relatives.
A unique tool in future breeding programmes is a test showing
the dogs’ genotype. At the moment DNA tests are available
for some monogenetic diseases, and in the near future such
tests will be available for an increasing number of diseases and
breeds. Studies of major genes affecting polygenetic diseases
will probably have great impact on future dog breeding. Recent
studies of HD and ED have reported strong indication for major
genes affecting HD and ED, suggesting that considerable genetic
progress might be possible by selection against the major gene
[12]. But there will probably always be important breed specific
health issues that cannot be measured by DNA tests or screening
results. These health issues must still play an important role in
breeding programmes.
to important breed specific health issues. The programme
should consist of both basic demands that must be fulfilled in
order to register puppies, and recommendations on how to
breed, how to select dogs for breeding and how to do the right
combinations. Eradication of genetic diseases and breeding only
genetically healthy dogs is a totally unrealistic goal. Too strict
regulations and demands in breeding programmes could have
the opposite effect, as it will exclude too many dogs, reducing
the breeding population and result in inbreeding. And if we,
theoretically, were able to breed genetically healthy dogs, could
we then be sure that these dogs were also functionally healthy?
Probably not. Breeding is more than mating; dogs are a lot more
than the combination of genes.
Breeding values and DNA results should not replace other
aspects in breeding programmes or the use of common sense,
but should be supplemental in reaching the common goal:
Functionally healthy dogs with a construction and a mentality
typical to the breed, dogs that can live a long and happy life to
the benefit of themselves, the owner and the society.
Education
Education of dog breeders is basic in order to succeed with a
breeding programme. The breeders have a large responsibility,
both to the dogs, the owners and society. Kennel clubs and
breed clubs must play an important role in educating breeders;
knowledge is vital to succeed. The education of breeders must
include important topics concerning raising puppies, not only
correct feeding, exercise etc, but the importance of socialisation
from the very early childhood, training puppies and young dogs
to give them the possibility to develop a healthy mentality. The
What is a breeding programme?
A breeding programme should be a guideline for breeders. Some
ethical aspects should be the same for every breed, in addition
64
Healthy dog breeding: A 10 weeks old Newfoundland puppy and his 13 years old grandmother enjoying breed typical work in the water.
breeder is responsible for selecting the right owner for the puppy.
A lot of problems and tragic events could have been prevented if
the breeder had been more selective when selling a puppy, and
more helpful with advice to the dog owner.
Cooperation, respect and honesty
2.
An important key to success is cooperation to the benefit of
dogs’ health. It is not enough for a breeder to cooperate with
his friends; there must be cooperation on every level: between
kennel clubs, breed clubs, breeders, veterinarians and scientists.
For cooperation to succeed we must respect and trust each
other; honesty is vital for success of any breeding programme.
Knowledge of results from screening and DNA-tests are
important, but it might be just as important to know about
the occurrence of other breed specific health issues which are
known or suspected to be inherited, but cannot be revealed by
screening or DNA-tests. To succeed in healthy dog breeding, it is
important to avoid the combination of dogs from families with
increased frequency of such diseases. This knowledge can only
be obtained through cooperation, respect and honesty.
The results of both screening and DNA tests should be registered
in a kennel club register, open to the public. A national disease
register based on veterinary clinical diagnoses which are linked
to the identification of the diseased dog, would be a great
additional help in breeding programmes [13].
3.
4.
5.
6.
7.
8.
A breeding programme based on knowledge, cooperation,
honesty, reliable results from screening and DNA-test, and
hopefully in the future also from a national veterinary disease
register, combined with other important health issues, including
mental health, should have every possibility to be beneficial for
healthy dog breeding.
9.
10.
Basic rules and recommendations for
breeding healthy dogs
1.
Only functionally, clinically healthy dogs should be used for
breeding; dogs with chronic diseases should never be bred
unless we know for sure that heritability plays no role in
causing the disease. If a dog suffers from a disease that is
suspected, but not proven, to be inherited, the dog should
not be bred. If close relatives of such a dog are used for
breeding, they should be mated to dogs from bloodlines
with low or no occurrence of the same disease or disorder.
The breeding programme should not exclude more than
50% of the breed; the breeding stock must be selected
from the best half of the population.
Avoid matador breeding. A basic recommendation should
be that no dog should have more offspring than equivalent
to 5% of the number of puppies registered in the breed
during a five year period.
A bitch that is unable to give normal birth, due to anatomy or
inherited inertia, should be excluded from further breeding
– no matter what breed.
A bitch that is unable to take care of the newborn puppies,
due to mentality or inherited to agalactia, should be
excluded from further breeding.
Dogs with a mentality atypical for the breed, for example
aggressive dogs, should be excluded from breeding.
Screening results for polygenetic diseases should be used
for preparation of an individual breeding value, based
on both national and international screening results. The
average breeding value for the combination should be
better than the average for the breed. Screening should
only be recommended for diseases and breeds where the
disease has a major impact on the dogs’ health.
Results from DNA tests should be use to avoid breeding
diseased dogs, not necessarily to eradicate the disease.
Breed specific health issues that cannot be diagnosed by
DNA-tests or screening programmes must be included in a
breeding programme.
The raising of puppies with correct feeding, environmental
exposure, stimulation by their mother, breeder and others
to develop social sense and response, must be the norm for
every breed and breeding.
If these simple basic recommendations are implemented
in breeding programmes, we would attain considerable
improvement of the dogs’ functional health.
65
The value of breeding programmes - A. Indrebo
National health committees
Each kennel club should have their own health committee, giving
advice to breed clubs on health issues. The Norwegian Kennel
Club (NKC) has very few registration restrictions and gives the
breed clubs considerable responsibility for detailed advices in
the breeding programmes. We put a lot of effort in educating
the breed clubs and the breeders. It is our belief that it is better
to include as many breeders as possible to be organized in the
kennel club and to educate them on how to breed healthy dogs,
instead of excluding too many dogs and too many breeders due
to heavy restrictions. We can only influence the breeders that
cooperate with the kennel club. In Norway a large majority of
pure bred dogs are registered in the kennel club, in many breeds
close to 100%.
‘05, 82% were diagnosed as free, and the average ED score
was 0.27. Is this the result of a successful breeding programme?
The main cause of the improvement is probably not genetic.
From 01.01.2000 the minimum age for official ED status in this
breed was lowered from 18 to 12 months, due to Scandinavian
harmonization. In the studies of Mäki et al [6], age was found
to be a highly significant factor influencing the score of ED.
As the ED score is based mainly on the amount of osteophyte
formation, it is not surprising that the score is improving when
dogs are examined at lower age. This is an example that shows
the importance of international harmonization; if the protocol
differs between countries, the screening results will not be
compatible, and preparation of international breeding values
would not be reliable.
The Nordic Kennel Union (NKU)
Another step towards better harmonization would be common
international education of HD and ED panellists.
The Scandinavian countries cooperate in health issues through
the NKU Scientific Committee. The members are mainly scientists
who are appointed by their kennel club. Subcommittees are
working with DNA-tests and breeding values for HD and ED.
NKU has an HD/ED panel, consisting of the veterinarians that
are responsible for reading radiographs for official HD and ED
diagnoses in each country.
The main issue of the NKU HD/ED Panel is to harmonize the
protocol for screening for these diseases in Scandinavia, and
hopefully this harmonization will be valid also in other FCI
countries. In March 2006 the Danish Kennel Club hosted a
conference for the FCI (Federation Cynologique Internationale),
with delegates and HD panellists from 26 FCI countries. The
main topic was to improve the FCI protocol for HD screening. In
June the FCI Scientific Commission appointed an expert group to
assist the commission by preparing a draft proposal for changes
based on suggestions put forward during the conference in
Denmark. At the FECAVA Congress in Dubrovnik in March 2007,
there will be a FECAVA HD Symposium with invited speakers
from the FCI Scientific Commission and their expert group.
Harmonization of the protocol for HD
and ED screening
To be useful in international breeding programmes, the score
from screening for HD or ED should be the same for the same
dog, no matter where the dog is radiographed or diagnosed.
Minimum age, position of the dog when radiographed,
technical demands, depth of sedation and the diagnostic scale
and criteria, should be uniform in every country.
Figure 1 shows the prevalence of ED in Bernese Mountain Dogs
in Norway from 1986-2005. In the period ’86-’97, 66% were
diagnosed as free, and the average ED score was 0.53. In 1999,
there was an obvious improvement of the ED status. From ‘99-
Screening for inherited eye diseases
The same eye disease should have the same diagnosis in every
country. This is an important issue both for the European College
of Veterinary Ophthalmologists (ECVO) and for the International
Working Group on Canine Eye Diseases (IWGCED), consisting of
Instead of having strict registration restrictions, the Norwegian Kennel Club put a lot of effort in educating the breeders through weekend seminars, both central seminars in Oslo and regional seminars throughout the country, with topics like behaviour, cynology, genetics,
breeding, raising puppies, different health issues etc. NKC have an excellent cooperation both with the Norwegian School of Veterinary
Science and the Veterinary Association. The NKC seminars are very popular, and may attract 300-500 participants, mainly breeders.
66
100
% elbow dysplasia
90
80
70
60
50
40
30
20
10
0
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
05
Registration year of the dog
Free (0)
Mild (1)
Moderate (2)
Severe (3)
Figure 1. The prevalence of elbow dysplasia (ED) in Bernese Mountain Dogs in Norway 1986-2005, based on radiographic screening.
Total number of dogs of this breed registered in this period is 5818, of which 3743 (64%) were examined. Prior to 2000, the minimum age
for radiographic examination for ED in this breed was 18 months. Due to harmonization of the protocol for the Scandinavian countries, the
minimum age was lowered to 12 month from 01.01.00. All dogs registered in 1999 could be diagnosed at 12 months, and some of the dogs
registered in 1998 could be diagnosed younger than 18 months. The puppies are normally registered at 5-10 weeks of age. (Data from the
Norwegian Kennel Club, May 2006, http://www.nkk.no).
in the registration number of the dog, and a complete form
containing all the dogs’ data, including the ID-number, is then
sent immediately by e-mail from NKC to the owner. By signing
this form, the owner allows the test result to be made public in
the database. The veterinarian confirms the dog’s identity. The
sample must be mailed by the veterinarian, not by the owner.
The test result is sent from the laboratory both to NKC and to
the owner (Figure 2).
both eye panellists and kennel club representatives. To succeed
in international harmonization, it is important to have common
education for eye panellists, which is already established in
Europe by the ECVO, and a common international form for
diagnosing and reporting the results of an eye examination
to the national kennel club database. ECVO has established a
uniform European Eye Certificate which is now in use in several
European countries, and will hopefully be used by an increasing
number of countries in the near future. A great advantage in
using the ECVO Certificate is that the certificate can easily be
recognized in most countries. The certificate also ensures the
quality of the examination, as only veterinarians recognized by
the ECVO are allowed to issue this certificate.
The results of DNA-tests can contribute to healthy dog breeding
as part of a breeding programme. We will know whether a dog
is:
a. free of the gene causing a recessive disease,
b. a carrier or
c. if it will develop the disease.
Through selective breeding where at least one parent of the
litter is free of the gene, we can be assured that the puppies will
not develop that particular disease. We do not have to exclude
the carriers from breeding. This is basic in NKC breeding policy.
DNA-tests
The number of available DNA-tests is increasing rapidly. To be
beneficial for healthy dog breeding, the DNA test must represent
a disease that is harmful to the dog; we must test the dogs
due to a health problem – not mainly because there is a test
available. The dogs must be identified with microchip or tattoo,
and all the results should be available to the breeders.
The kennel club database open to the
public
In Norway the veterinarians employed by the NKC decide,
together with the breed club, which of the available DNA-tests
that are valuable for the breed, and then make an agreement
with a laboratory that will do the testing. A specific form
can be obtained from the NKC database; the dog owner fills
Access to information concerning the individual dog, its ancestors
and offspring is important in every breeding programme. The
NKC database contains all available information on any dog
registered the last 30 years. The database is open to all members
of the NKC, breed clubs and veterinarians. Pedigrees, individual
67
The value of breeding programmes - A. Indrebo
results from screening for HD, ED and inherited eye diseases,
results from DNA-tests as well as results from dog shows and
other official competitions like obedience, hunting etc can be
obtained from the database.
when performing their work in the show ring. A judge may easily
contribute to making a dog a nuisance by putting up or even
promoting “over-typing”, which may lead to health damage as
a consequence [14].
Breed standards and judges
Improvement in the breed standards and increasing the
awareness of the judges to recognise their responsibility
concerning health issues, will have considerable impact on the
value of breeding programmes, as the breed standard and the
judges’ interpretation of the standard always will be a major
guideline in the breeding of pure bred (pedigree) dogs.
The last couple of decades there have been major improvements
in many FCI breed standards concerning healthy anatomy. The
European Convention for Protection of Pet Animals, that was
concluded in Strasbourg in 1987 and registered by the SecretaryGeneral of the Council of Europe in 1994, has been significant
in the progress of this work. In addition to alter specific breed
standards towards the description of a healthier and more
functional anatomy, the following sentence has been included
in all FCI breed standards since 2003: “Any dog clearly showing
physical or behavioural abnormalities shall be disqualified”.
Summary
Breeding programmes can be valuable for breeding functionally
healthy dogs. These programmes should be guidelines and not
contain too stringent demands. Every dog should be identified
with chip or tattoo. The protocol for screening as well as the
education of panellists should be the same in all countries, and
national and international breeding values should be applied
for polygenetic diseases. Results of DNA-tests should be used
to avoid breeding diseased dogs, not necessarily to eradicate
the genes that cause the disease. Breed specific health issues
that cannot be measured through screening programmes
There is no doubt that the judges have large influence on the
selection of dogs that will be used for breeding, and therefore
on the health and welfare of pure bred dogs. In an article in
the FCI Magazine in 2003, Uwe Fisher, an international judge
and member of the main board of the FCI, on behalf of the
FCI strongly requested the judges to recognise this responsibility
Figure 2. Procedure for central registration of results from DNA-tests in the Norwegian Kennel Club (NKC). (1) The owner logs on to the NKC
web services, fills in his e-mail address and password and orders a form for DNA analysis. (2) He fills in the registration number of the dog, and
all registered data concerning the dog are shown on the screen. After checking the data, he presses “send”. (3) Within few minutes he receives
on e-mail the form “Requesting for DNA testing” with all the data concerning the dog (breed, name, sex, registration number, ID-number, date
of birth) and the owner (name, address, telephone and e-mail address) filled out. (4) The owner brings the dog and the form to the veterinarian,
who takes the blood sample, confirms the dogs ID-number and fills out the sample information on the form. The owner signs the form to confirm
that he accepts the terms and conditions of the laboratory, and that the test result will be registered in the NKC and made public. (5) The
veterinarian (not the owner) mails the sample and the form to the laboratory. (6) The test result is sent both to the owner and NKC.
5
Veterinarian
Laboratory
Mail
Form +
Sample
6
Test result
4
u
es
r
st
Te
lt
nkk.no
2. Fill in the registration number
3. A form for the specific
disease, containing all
the dogs’ registered data,
returned by e-mail
1
Dog owner
68
Norwegian
Kennel Club
NKC
Database
or DNA tests, should still play an important role in breeding
programmes. When selecting dogs for breeding, the dog and
the breed should be looked upon in its entirety. Heavy selection,
strict restrictions and inbreeding should be avoided, and genetic
variance in a breed must not be further reduced. The goal in
healthy dog breeding should be functionally healthy dogs with
a construction and a mentality typical to the breed.
References
[1]
[2]
[3]
[4]
[5]
[6]
HEDHAMMAS (A.), OLSSON (S.E.), ANDERSSON (S.A.), PERSSON
(L.), PETTERSSON (L.), OLAUSSON (A.), SUNDGREN (P.E.) Canine hip dysplasia: Study of heritability in 401 litters of German
Shepherd dog. J. Am. Vet. Med. Assoc., 1979, 174: 1012-1016.
LINGAAS (F.), HEIM (P.) - En genetisk undersøkelse av hofteleddsdysplasi i norske hunderaser. Nor. Vet. T., 1987, 99: 617-623.
LINGAAS (F.), KLEMMENTSDAL (G.) - Breeding values and
genetic trend for hip dysplasia in the Norwegian Golden Retriever
population. J. Anim. Breed. Genet., 1990, 107: 437-443.
SWENSON (L.), AUDELL (L.), HEDHAMMAR (A.) - Prevalence and
inheritance of and selection for hip dysplasia in seven breeds
of dogs in Sweden and benefit:cost analysis of a screening and
control program. J. Am. Vet. Med. Assoc., 1997, 210: 207-214.
OHELERT (S.), BUSATO (A.), GAILLARD (C.), FLÜCKIGER (M.),
LANG (J.) - Epidemiologische und genetische Untersuchungen
zur Hüftgelenksdysplasie an einer Pupulation von Labrador
Retrievern: Eine Studie über 25 Jahre. Dtsch. tierärztl. Wschr.,
1998, 105: 378-383.
MÄKI (K.), LIINAMO (A.-E.), OJALA (M.) - Estimates of genetic
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
parameters for hip and elbow dysplasia in Finnish Rottweilers. J.
Anim. Sci., 2000, 78: 1141-1148.
OHLERTH (S.), LANG (J.), BUSATO (A.), GAILLARD (C.) - Estimation
of genetic population variables for six radiographic criteria of hip
dysplasia in a colony of Labrador Retrievers. Am. J. Vet. Res.,
2001, 62: 846-852.
GRONDALEN (J.), LINGAAS (F.) - Arthrosis in the elbow joint of
young rapidly growing dogs: a genetic investigation. J. Small
Anim. Pract., 1991, 32: 460-464.
SWENSON (L.), AUDELL (L.), HEDHAMMAR (A.) - Prevalence
and inheritance of and selection for elbow arthrosis in Bernese
Mountain Dogs and Rottweilers in Sweden and benefint:cost
analysis of a screening and control program. J. Am. Vet. Med.
Assoc., 1997, 210: 213-221.
BEUING (R.), JANSSEN (N.), WURSTER (H.), SCHMIED (O.),
FLÜCKIGER (M.) - Untersuchungen zur züchterischen Bedeutung
der Ellbogendysplasie (ED) beim Berner Sennenhund in
Deutchland. Schweiz. Arch. Tierheilk., 2005, 147: 491-497.
JANUTTA (V.), HAMANN (H.), KLEIN (S.), TELLHEIM (B.), DISTL
(O.) - Genetic analysis of three different classification protocols
for the evaluation of elbow dysplasia in German shepherd dogs.
J. Small Anim. Pract., 2006, 47: 75-82.
MÄKI (K.), JANSS (L.L.G.), GROEN (A.F.), LIINAMO (A.-E.), OJALA
(M.) - An indication of major genes affecting hip and elbow
dysplasia in four Finnish dog populations. Heredity, 2004, 92:
402-408.
INDREBO (A.) - Breeding healthy dogs - a breeders perspective.
EJCAP, 2005, 15: 17-21.
FISCHER (U.) - We are responsible. FCI Magazine, 2003, vol. 2,
5-7.
Segregation analysis to determine
the mode of inheritance
O. Distl University of Veterinary Medicine Hannover, Institute of Animal Breeding and Genetics, Bünteweg 17p, D-30559 Hannover,
Germany E-mail:[email protected]
INTRODUCTION
Many disorders in animals are observed more frequently in certain breeds and within breeds more often in the
same families. Familiarity is assumed for a disorder when families are observed with more than one affected family
member. Familial disorders may have a genetic contribution. The same is often claimed for disorders which show a
breed disposition. On the other hand, genetically caused diseases may not necessarily lead to breed differences in
incidence but will contribute to variation among families within breeds. A useful starting point for answering the
question whether a disorder is inherited is by drawing pedigrees to provide an initial impression of the distribution
of affected and non-affected animals and how frequently the disorder is transmitted from one generation to the
next. General evidence for genetic contribution to a disorder is given when environmental factors can be excluded
as the only responsible causes for a disorder and a significant proportion of the phenotypic variation of a disorder
can be explained by genetic models. With increasing molecular genetic data, the type of gene action based on known
DNA sequence variation can be characterized by individual genes and the nature of complex genetic traits can be
understood much better.
The presentation will give an overview on the model components included in estimation of the mode of inheritance
based on phenotypic data and further developments for incorporation of molecular genetic data into the analyses.
Segregation analysis
segregation analyses often encounter problems when different
mating types have to be considered and several hypotheses are
more or less likely. Complex segregation analyses have been
developed to allow for more factors to vary and to reduce the
restrictions on assumptions to be made for the model tested.
Methods used to solve the likelihood functions are based on
maximum likelihood or Markov chain Monte Carlo approaches
(Gibbs sampling).
Segregation analysis is employed to determine whether familial
data for particular disorders or other traits are compatible with
specific modes of inheritance. Modes of inheritance tested in
segregation analyses include monogenic (Mendelian), digenic
or polygenic models. In addition, age of onset, sex effects and
sampling scheme can be taken into account besides the specific
genetic hypothesis under consideration. Simple segregation
analysis tests the segregation parameter ⍜ under a specified
sampling scheme and mating type. Pedigrees used for segregation
analysis may be from specifically planned matings or randomly
sampled pedigrees with arbitrary structure or sampled through
ascertained cases in clinics or veterinary practice. Arranged
matings among animals can be more easily tested for specific
modes of inheritance than pedigrees with arbitrary structure,
missing data and many inbred animals. In the case of a rare
disease and an autosomal dominant hypothesis, the segregation
ratio ⍜ is assumed to be 0.5 as families segregating for the trait
are most likely composed by matings of heterozygous affecteds
and homozygous non-carriers. As far as the segregation ratio is
not significantly different from ⍜ = 0.5, this mode of inheritance
is accepted. Different methods for estimating ⍜ have been
developed and are easily applied (Singles Method, Weinberg’s
General Proband Method). These simple approaches to
Complex segregation analysis
Complex segregation analysis is based on a mathematical model
that incorporates several, functionally independent components
to accommodate for arbitrary mating types, different modes of
monogenic or oligogenic inheritance (major genes), to allow
for polygenic variation and non-genetic variation in addition to
major genes and different data types such as binary, categorical
and continous data. In addition, age of onset of a disease and
sampling scheme (random pedigrees versus non-randomly
selected pedigrees) can be modelled. The basic model as
formulated in the Elston-Stewart algorithm was the basis for the
more complex models. The Elston-Stewart algorithm included
a component describing the joint distribution of genotypes
of mating individuals whereby these genotypic distributions
71
Segregation analysis to determine the mode of inheritance
stem from a single locus with two alleles (monogenotype),
a few loci with each two alleles (oligogenotype) or from a
polygenotypic distribution with an infinite number of genotypes
(polygenotype). The second component of the Elston-Stewart
algorithm specified the relationship between the genotypes and
phenotypes, separately for each genotype (penetrance function).
Mathematically, the phenotype investigated is modelled as a
conditional probability on the genotype underlying the model
used. The simplest genetic model for a dichotomous trait and
a monogenic autosomal inheritance of two alleles is then
completely defined by the following genotype to phenotype
relationships: gAA (1) = gAa (1) = 1, gaa (1) = 0 and gAA (0) = gAa (0)
= 0, gaa (0) = 1, where the conditional probability equals unity
when for the genotypes AA and Aa the phenotypic outcome
is affected (=1) and for the genotype aa the phenotypic status
is unaffected (=0). Similarly, if a completely penetrant recessive
trait is assumed, we have the following conditional distributions:
gaa (1) = 1, gAa (1) = gAA (1) = 0, gaa (0) = 0, gAa (0) = gAA (0) = 1.
Two- or three-locus models give raise to much more models
(phenogrammes) how the oligogenotype is related with the
phenotype. If we do not wish to assume complete penetrance
we can introduce for each distinct genotype or groups of
genotypes a specific penetrance. For X-linked loci, the conditional
distributions of phenotypes have to be defined for males and
females separately. Furthermore, traits only expressed in males
or females can be modelled via the penetrance parameter
allowing fully expressed traits only for one sex. Just as the
phenotypic distribution may be sex-dependent, so the disorder
considered has a variable age of onset and thus the observation
whether the disorder is expressed, depends upon the age at
examination of each individual. Then the probability that an
individual with a genotype AA, Aa or aa is affected by a specific
age depends of the age-related susceptibility of the genotype to
the disorder. When we turn to polygenotypes, we use normal
distribution functions. In the case of a binary or categorical
phenotype, this model corresponds to the threshold or liability
model. The polygenotypes are normally distributed with genetic
variance σ2G and residual variance σ2E. An individual is affected
or mildly/severely affected whose liability is greater than the
threshold. The threshold may also depend upon the genotype
of an additional monogenic locus.
The mode of inheritance can be described how the genetic
variability is passed on from one generation to the next and is
summarized mathematically by the genotypic distributions of
the offspring in dependence upon the parental genotypes. Let
us assume that an individual has parents with genotypes s and
t, then the conditional probabilities for the genotypes of this
individual can be viewed as elements of a stochastic matrix called
the genetic transition matrix, probability (P) for the individual
genotype given genotypes of parents s and t, P(gi|gF,gM). All types
of monogenic and oligogenic inheritance can be parameterized in
terms of transmission probabilities. In the autosomal monogenic
model with alleles A and B, the transmission probabilities are
the probabilities that an individual with genotype AA, AB or
BB transmits the allele A to offspring. Using the definitions for
the transmission probabilities τAA =1, τAB =0.5 and τBB =0, the
probabilities for the genotype AA of the individual with parents s
and t are equal to τsτt, the probabilities for the genotype AB with
parents s and t are equal to τs (1-τt) + τt (1-τs) and the probabilities
for the genotype BB with parents s and t are equal to (1-τs)(1-τt).
Extension to several unlinked loci and linked loci is straightforward.
Linked loci require recombination rates among loci as further
parameters. Polygenic inheritance using an additive model can
be modelled through the transmission of the gametic values
being 0.5 for any polygenotype. The polygenotypes of offspring
are produced by the mid-parents´ values of their polygenotypic
effects with variance σ2G /2.
Sampling scheme describes the way how individuals were selected
from the population for study. Random sampling means that
we take a random sample of individuals from a population and
then augment this sample by including all or a random sample
of relatives up to a certain degree of relatedeness. When well
designed recording schemes are introduced, random samples
of progeny or sibships with their ancestors can be collected.
These samples can be collected in a specific geographic area
which is not critical as long as individuals outside this area are
not selected according to their phenotype or genotype. Rare
conditions are hardly studied in random samples hence many
uninformative families are collected. Typically for this situation,
families are included in the study because at least one member
of the family is affected. The kind of the non-random sampling
procedure is characterized by the type of ascertainment.
Complete ascertainment is given when a sibship enters the
sample independently of the number of additional affected
members. The opposite extreme to complete ascertainment is
single ascertainment. The probability for an affected individual
tends to be zero to be brought into the study when there is
not more than one affected family member. Incomplete multiple
ascertainment is the situation between single and complete
ascertainment. To ensure a valid segregation analysis, the kind
of ascertainment should be identified. Methods of estimation
of the segregation ratio depend on how the families have been
brought into the study. A likelihood function based on the
components of the segregation analysis model can be derived
and maximized for the data observed. Since the likelihood
function includes the different types of genetic models as
well non-genetic factors, submodels can be tested against the
most general model. Inferences can be performed for both
continuously and categorically distributed data and genetic
models that include monogenic, digenic, polygenic and mixtures
of monogenic and polygenic as well as oligogenic and polygenic
models. A genetic background of a trait analysed is given when
the model explaining only non-genetic factors can be rejected
and models including genetic components explain a significant
proportion of the phenotypic variation.
A likelihood ratio test statistic is used to compare a specific
null hypothesis (H0) defined by a specific model (restricted
model) against a most general (not restricted) model. The test
statistic asymptotically follows a χ2-distribution, and significance
levels can be obtained by using this distribution. Degrees of
freedom are given by the difference of independently estimated
parameters for the models compared. The information criterion
of Akaike (AIC) can be used as an additional measure to choose
the sparsest model with the best fit to the data. The model with
the smallest AIC fits the data best with a minimum number of
parameters but all hypotheses that cannot be rejected against
the most general model using the likelihood ratio test must also
be considered as possible. The AIC criterion cannot be used to
exclude a hypothesis if this model was not rejected against the
most general model by using the likelihood ratio test.
72
sampling can be employed to estimate non-genetic effects,
genotype frequencies and their associated genotypic effects and
quantitative genetic variation including all relationships of the
animals. When information for genetic markers in populationwide linkage disequilibrium or mutations of genes associated
with trait variation can be included in the analysis, the genotypic
distributions need no longer to be estimated and inferences on
the genotypic effects are much more precise. Such genetic
polymorphisms enable us to model the gene actions and their
interactions in networks for complex genetic traits.
Conclusions
Complex segregation analysis is a powerful tool to detect
major gene variation. Quantitative genetic models rely on the
assumption of many (infinite) loci with very small and equal
effects. This model is severely compromised in the presence
of segregation of major genes. Extensions and improvements
of algorithms made to the simple segregation models allow
to estimate major genotype effects in the framework of the
methodology developed for quantitative genetic analysis. Gibbs
73
Breeding for improved health in
Swedish dogs
S. Malm Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, P.O. Box 7023, S-75007 Uppsala.
E-mail: [email protected]
INTRODUCTION
In Sweden there are about 950.000 dogs, 85% of which are purebred and registered in the Swedish Kennel Club (SKC).
Furthermore, a large proportion of Swedish dogs have a health insurance. Thanks to the extensive registration and
insurance of dogs in Sweden, large amounts of data regarding morbidity, mortality, and ancestral background are
being collected and made available to breeders and scientists. These databases are valuable tools for breeders and
breed clubs in selection of breeding stock and in breeding planning. They also offer unique possibilities for both
epidemiological and genetic studies on different diseases in dogs.
Genetic Health Programmes
as maintaining possibilities for sustainable breeding with respect
to genetic variation. However, so far genetic health programmes
for physical health have been developed only for diseases
with well defined and validated methods for examination and
diagnosis. Many breeds have other, less well defined, inherited
conditions that may have a larger impact on the dogs’ health.
It is therefore important not to put too much focus on one or
a few diseases only, just because they are easy to diagnose and
to record. Because genetic health programmes only cover some
aspects of mentality and functionality, most breed clubs have
additional recommendations or restrictions in their breeding
policies.
The SKC started to develop genetic health programmes more
than 25 years ago. Records from these programmes are stored
in the SKC database and are freely accessible through the
SKC web site. The first programmes concerned hip and elbow
dysplasia (HD and ED). Today, numerous breeds are included in
a genetic health programme for HD or ED, implying that hip or
elbow status of both the sire and the dam should be known for
the offspring to be registered in the SKC. In many breeds, an
additional requirement is that dogs should be free from HD to
be accepted for breeding.
In addition to HD and ED, genetic health programmes for other
inherited conditions, such as hereditary eye diseases, have been
developed. These are based on breed-specific needs and have
been introduced on request from the breed clubs.
New tools
Development of breeding strategies
Breeding of dogs is regulated both on international and national
levels. In addition to breed specific genetic health programmes, all
members of the SKC are obliged to follow the general regulations
and breeding policy set up by the SKC. These documents give
general restrictions, guidelines, and goals for breeding of dogs.
However, there are almost 300 different breeds in Sweden and
each breed has its own specific conditions that are important
to consider in the breeding programme. Therefore, in 2001 the
SKC decided that each breed should have their own breeding
strategy, taking into account all aspects relevant in the breeding
goal for that specific breed. Thus, the breeding strategy should
consider and prioritize between aspects of both physical and
mental health, also taking the population structure and genetic
variation into account. Breed-specific goals and strategies to
achieve these goals should be included, constituting an overall
plan for the breed. The responsibility for developing these
strategies was given to the breed clubs, and at present more
than 140 clubs have submitted a breeding strategy to the SKC.
Besides physical health, the SKC has developed programmes with
respect to mental health and management of genetic variation.
Since 2002, all breeds belonging to the Swedish Working Dog
Association are obliged to undergo a standardised behavioural
test (dog mentality assessment), describing the mental status of
the dog, before being used in breeding. Furthermore, Border
Collies need to undergo a working test for evaluation of their
herding skills if the progeny are to be registered in the SKC.
Management of genetic variation is important to avoid loss
of genetic diversity, manifestation of recessive defects and
inbreeding depression. In some Swedish breeds, limitations for
the maximum number of offspring allowed for a single male
have been introduced to avoid extensive use of popular sires.
Also, programmes for out-crossing with individuals from closely
related breeds have been developed in order to increase the
effective population size and improve health traits.
In conclusion, the genetic health programmes currently operated
by the SKC aim at improved physical and mental health, as well
75
Breeding for improved health in Swedish dogs - S. Malm
Breeding value prediction
Despite efforts to reduce the frequency of HD and ED by
means of genetic health programmes, based on radiographic
examination of the phenotype and subsequent mass selection,
the improvement has been disappointing in several breeds. As
an example, Figure 1 shows the phenotypic trend for HD in
Swedish Rottweilers and Bernese Mountain Dogs born during
1984-2001. Low or no improvement in HD has been reported
also by other countries.
a week. Only dogs with their own screening record will get their
breeding value published, together with the accuracy of the
prediction.
A strategy for implementation of the breeding values in the
overall breeding programme for each breed is needed. Other
traits included in the breeding strategy need to be considered
relative to HD or ED. Besides, the relationship between individuals
selected for breeding must be considered to avoid increased
inbreeding due to selection of close relatives.
Breeding value prediction can be a useful tool for genetic
evaluation of traits other than HD and ED. Genetic improvement
not only of other diseases, but also behavioural and functional
traits, could probably be enhanced by selection on breeding
values instead of phenotypes.
In grading systems for HD and ED there are limited possibilities
for measuring differences among phenotypically normal dogs.
In some breeds, a large proportion of the dogs are free from
dysplasia which makes selection based on the phenotypic value
alone inefficient. In addition, the phenotype is affected by
various systematic environmental factors, e.g., age at screening.
Also the type of chemical restraint, used for sedation during
radiographic examination of HD, has an impact on the diagnosis
of hip status. The effect of different environmental factors on
evaluation of hip and elbow status implies that the individual’s
own screening result alone may be inaccurate for selection
purposes.
Genetic evaluation using mixed linear models (often called BLUP)
for prediction of breeding values have been used extensively in
breeding of cattle, horses, poultry and swine for several years.
However, in dog breeding this methodology has been used only
to a limited extent. Prediction of breeding values for HD and ED
would enable a more accurate comparison of genetic merit of
dogs. The BLUP method makes use of all available information
about relatives and simultaneously adjusts for environmental
effects. Selection against HD and ED based on predicted
breeding values has already been introduced in some countries,
e.g. Finland and Germany. In Sweden, the SKC is planning to
implement breeding value prediction for HD and ED as a routine
for a number of breeds during 2007.
A genetic study of HD and ED has been conducted in two
breeds, Rottweiler and Bernese Mountain Dog, to estimate the
amount of genetic variation in HD and ED, and to assess genetic
trends. Based on these results, a statistical model for routine
prediction of breeding values for HD and ED in Swedish dogs
was suggested. The next step will be to evaluate the model also
for other breeds.
The genetic evaluations of HD and ED in Sweden will be managed
by the SKC and breeding values will most likely be updated once
DNA tests for canine disorders
Advances in molecular genetic studies of the dog and the
availability of the canine genome sequence imply that an
increasing number of the genes underlying diseases in dogs are
being revealed. The development of DNA tests for different gene
mutations makes it possible to accurately predict the genotype
of an individual dog with respect to a specific disease, i.e. to
identify genetically normal, carrier and affected animals. The
possibility of identifing carriers of a defective allele enables a
more subtle management of breeding programmes to decrease
the frequency of a particular disease gene without unnecessary
reduction of the overall gene pool.
The SKC currently records results from DNA tests for canine
leukocyte adhesion deficiency (CLAD) in the Irish Setter,
congenital stationary night blindness (CSNB) in the Briard,
von Willebrand disease in the Kooikerhondje and one type of
progressive retinal atrophy (prcd-PRA) in a number of breeds. All
results are published on the SKC web site for anyone to access
and genetic health programmes based on the DNA testing are
developed for each breed individually.
Internet based breeding statistics
The SKC has recently developed an internet based service
including breeding statistics for both individual dogs and for
each breed as a whole. The statistics are based on results from
genetic health programmes, the dog mentality assessment,
official competitions, and dog shows, as well as pedigree
information. For individual dogs, own records as well as statistics
for littermates, full-sibs and offspring are available. Also, the
pedigree and coefficient of inbreeding is shown for each dog.
The population-wide information for each breed includes
statistics on number of registrations, health traits, mental
status, breeding animals (regarding number of offspring and
grandchildren per sire or dam, litter size, and age at breeding)
and average levels of inbreeding by birth year. Furthermore, the
service contains an option to calculate the expected inbreeding
coefficient for offspring resulting from a planned mating.
This tool is available to anyone through the SKC web site and
is very useful to breeders for genetic evaluation and selection
of breeding animals. It also allows for breed clubs to assess the
overall situation in the breed.
NON-AFFECTED (%)
Figure 1. Distribution of Rottweilers and Bernese Mountain Dogs
not affected with hip dysplasia (HD), in relation to birth year.
76
Conclusion
LEPPÄNEN (M.), SALONIEMI (H.) - Controlling canine hip dysplasia in
Finland. Prev. Vet. Med. 1999, 42: 121-131.
LINGAAS (F.), HEIM (P.). - En genetisk undersøkelse av hofteleddsdyplasi
i norske hunderaser [Genetic investigation on hip dysplasia in
Norwegian dog breeds]. Norsk Veterinærtidsskrift, 1987, 99:
617-623.
MALM (S.), DANELL (B.), AUDELL (L.), STRANDBERG (E.), SWENSON
(L.), HEDHAMMAR, (Å.) - Impact of sedation method on the
diagnosis of hip and elbow dysplasia in Swedish dogs. Prev. Vet.
Med., 2006, In press.
MÄKI (K.), LIINAMO (A.E.), OJALA (M.) - Estimates of genetic
parameters for hip and elbow dysplasia in Finnish Rottweilers. J.
Anim. Sci., 2000, 78: 1141-1148.
SWENSON (L.), AUDELL (L.), HEDHAMMAR (Å.) - Prevalence and
inheritance of and selection for elbow arthrosis in Bernese
Mountain Dogs and Rottweilers in Sweden and benefit:cost
analysis of a screening and control program. J. Am. Vet. Med.
Assoc., 1997, 210: 215-221.
SWENSON (L.), AUDELL (L.), HEDHAMMAR (Å.) - Prevalence and
inheritance of and selection for hip dysplasia in seven breeds
of dogs in Sweden and benefit:cost analysis of a screening and
control program. J. Am. Vet. Med. Assoc., 1997, 210: 207-214.
WILLIS (M.B.) - A review of the progress in canine hip dysplasia control
in Britain. J. Am. Vet. Med. Assoc. 1997, 210: 1480-1482.
Dog breeding is of concern not only to individual breeders, but
also to breed clubs, kennel clubs, geneticists, veterinarians, and
authorities. Sustainable breeding of healthy dogs is facilitated
by cooperation between the different parties and agreement
about the breeding goals. In addition, genetic evaluation and
selection must be based on accurate information about the
individual animals and the breed as a whole. Recording of traits
considered to be of importance is therefore essential, as well
as pedigree information to enable evaluation of population
structure and studies of the mode of inheritance for different
traits. Consequently, the access to information and tools that
enhance genetic evaluation is of great value. The development
of breed-specific breeding strategies constitutes a solid basis for
a comprehensive and long-term breeding programme.
Relevant literature
DISTL (O.), GRUSSLER (W.), SCHWARZ(J.), KRAUSSLICH(H.) - Analysis
of Environmental and Genetic Influences on the Frequency of Hip
Dysplasia in German Shepherd Dogs. J. Vet. Med. A, 1991, 38:
460-471.
77
RADIOLOGY
FECAVA LECTURE
How to look at radiographs
C.R. Lamb(1)
SUMMARY
Errors in radiology may result from poor radiographic technique, failures of perception, lack of knowledge and
misjudgements. It is necessary to teach students how to interpret radiographs and teaching is likely to be most effective
when it enables students to see more clearly what a radiologist does by making their thought processes more explicit.
Compared to the traditional directed search method for examining radiographs, there are advantages in teaching a
hypothesis-driven search method in which students are encouraged to ask themselves simple questions about the
radiograph based on what they may know about the patient or their initial observations of the radiograph. The answers
to these questions may be used as a basis for forming hypotheses that influence the direction of further searches for
information, and help build up an understanding of what and what features fit together and what diagnosis is most
likely. This approach recognises the importance of using the clinical history when interpreting radiographs.
This paper is based on the FECAVA Lecture delivered
Avoiding errors in radiology depends on a variety of measures:
– false negative results may be minimised by making good
quality radiographs, by including all the relevant anatomy
and by looking carefully at the films.
– false positive results may be minimised by making good quality
radiographs and knowing about all the common anatomical
variations that occur between and within species.
at the 12th FECAVA/30th WSAVA Congress in Prague.*
What are the pitfalls?
In an ideal world, the results of diagnostic tests would always
be true. Ideal diagnostic tests would always give a positive
result in patients with the disease, and would always be
negative in unaffected patients. Unfortunately, the practice of
medicine is not perfect and false test results are encountered
frequently. Radiology is not immune from this problem. Errors in
radiology may result from poor radiographic technique, failures
of perception, lack of knowledge and misjudgements. [1-4]
Examples include:
– false negative results may occur when a lesion is not visualised
because it is subtle or superimposed on complex anatomical
features.
– false positive results may occur if a normal structure is
misinterpreted as abnormal, a film fault occurs that mimics
disease (figure 1) or if a measurement of a normal organ is
outside the reference range.
– true positive, but misclassified results occur when a lesion is
recognised but is interpreted incorrectly.
Studies have shown that final-year medical and veterinary
students tend to overinterpret normal radiographs. [5,6] This
tendency probably reflects a lack of knowledge of radiographic
anatomy, fear of missing an important abnormality, and an
unrealistically high expectation that radiographs are abnormal.
It is evident that it is necessary to help students learn how to look
at radiographs. This involves training the brain, not improving
vision. There is no need to have particularly good vision because
ability to extract information from radiographs is not based on
simple observation. The key point to recognise here is that there
is no observation without interpretation. Even interpretation
of the non-imaging clinical context in which the radiographs
were made is crucial to understanding what they mean. Expert
radiological ability principally requires skill in interpretation, but
an expert may take for granted aspects of their technique that
(1) Address correspondence: Mr. C.R. Lamb, Department of Veterinary Clinical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms,
Hertfordshire, GB-AL9 7TA. E-mail: [email protected]
* Hosted by CSAVA (Czech Republic) held in Prague 10 -14 October 2006
79
How to look at radiographs - C.R. Lamb
A
B
Figure 1. Example of poor radiographic technique contributing to a false positive diagnosis. A) Detail of a lateral abdominal radiograph of
a cat with renal insufficiency was interpreted as showing multiple small calculi in the ureters and bladder (arrows). B) Repeat radiograph
a few days later shows no signs of calculi, no crystals were found in the urine, and there were no signs of calculi or urinary obstruction on
ultrasonography. The initial erroneous diagnosis was probably the result of artifacts caused by damaged screens, debris in the cassette or a
processing fault.
a novice may not appreciate. Hence, one of the key aspects of
teaching that will make it more effective is helping students to
see more clearly what a radiologist does by making more explicit
the thought processes used by experts. [7]
radiograph with short excursions to examine in more detail
regions that they suspect might be abnormal. [8] Radiologists
routinely take steps to ensure optimal viewing conditions, such
as blacking out bright parts of the viewbox. Many radiologists
stand back from the viewbox to gain an overall impression of
the radiograph before moving closer to examine it in more detail
(figure 2).
Radiologists have generic visual abilities that enable them to
quickly recognise anomalies in images that are either radiological
or non-radiological in nature. [9] In radiologists, particularly
high levels of neuronal activity occur in parts of the brain used
to retrieve reference images from memory and for generation
of mental representations, which are used to construct a threedimensional mental version of the two-dimensional images.
[9] The neural activity involved in the interpretation of images
develops in response to training, usually over a period of several
years.
How do experts look at radiographs?
Even before looking at any radiographs of a patient, a radiologist
will have engaged in non-image based interpretation, considering
the answers to questions that help establish the context within
which diagnostic imaging will occur. [7] For example, what do
the patient’s signs suggest? What do the laboratory results
reveal? What kind of imaging will be most helpful? The answers
to these questions help the radiologist to form an opinion about
the probability that the radiographs will be abnormal.
Once radiographs have been obtained, it is necessary to search
them for signs of disease. Many radiologists scan the entire
Figure 2. Radiologists often stand back from the view box to gain an overall impression of the radiograph (A) before moving closer to
examine it in more detail (B).
A
B
80
Figure 3. Simplified example of a directed search pattern in a dog with suspected pulmonary disease. A) Initial search in which the observer
attempts to examine all the imaged anatomy by following a predetermined sequence unaffected by an obvious feature; B) subsequent
examination of obvious feature.
how to search films for abnormalities. Opinions tend to fall in
two categories:
– Look at structures according to a preconceived sequence.
This is known as a directed search pattern.
– Form a hypothesis about the possible diagnosis from the
patient’s history or from the initial observation of the film,
then use this to guide further examination of the radiograph.
This approach is known as a hypothesis-driven search.
When interpreting images, radiologists use non-image-based
information to invoke a diagnostic schema that controls their
radiographic interpretation by enabling possible interpretations to
be weighed against the probability of disease. [9,10] Recognition
of abnormalities involves observing image features and making
decisions about the probability that the features represent a
true positive finding with specific meaning. [11] It is thought
that examining a radiograph involves making decisions about
visual features at a rate of approximately one per second. [12]
Integration of non-image-based information and observations
of the radiographs result in a recognition of the radiographic
features most likely to be related to the patient’s condition.
The principle of the directed search pattern may be summarised
as follows:
– Examine the radiograph(s) in a predetermined sequence. For
example, start with the periphery of the film and gradually
move towards the middle, noting all structures along the
way (figure 3). This sequence is usually based on personal
preference; it does not rely on knowing the patient’s history.
– If you immediately spot an obvious lesion, try to ignore it until
you have completed your usual search sequence for all the
anatomy depicted on the radiograph. Part of the rationale
for a directed search pattern is that by avoiding concentrating
on a central or obvious abnormality, the chances of missing a
peripheral or unexpected lesion will be minimised.
– Examine the most obvious lesion last
– Collect up all signs and formulate a diagnosis
How should radiographic interpretation be taught?
Once good quality radiographs have been made, they must
be searched carefully for signs of disease. A principle that all
radiologists will agree about is the need to always examine the
entire radiograph. This need arises because we cannot always
predict the position of lesions based on the clinical signs.
Furthermore, some lesions may be suggested by the history, but
others may be unexpected because many common diseases,
such as trauma or neoplasia, have unpredictable patterns.
The next question that arises is in what order should the
various parts of the radiograph be examined? There are major
differences of opinion between teachers of radiology about
It is usual for undergraduates and radiology residents to be
taught a directed search pattern [13] and this approach is
81
Figure 4. Simplified example of a hypothesis driven search in a dog with suspected pulmonary disease. A) Initial observation of obvious
feature leads to the decision that it is probably a pulmonary mass; B) Need to assess if pulmonary mass is solitary or part of a multifocal
process prompts subsequent search of the remaining lung for additional lesions. Additional pulmonary lesions are found. Further searches
of the radiograph(s) will occur according to the updated interpretation of the possible significance of these findings.
Over many years spent in the company of students learning to
interpret radiographs, I have found that students who initially
fail to observe certain radiographic abnormalities can often
find them easily if prompted by an open-ended question about
the patient or the likely clinical scenario. To take a very simple
example, when discussing a radiograph of a dog with a partially
collapsed left lung, asking a question about how the dog was
positioned or restrained for radiography often prompts the
student to think of the possibility that the dog was anaesthetised
and, having thought of that possibility, they immediately observe
the tip of the endotracheal tube that had previously eluded their
gaze. The possibility that the dog has unilateral lung collapse
because of lateral recumbency under anaesthesia is then added
to the differential diagnosis, followed quickly by the notion that
this possibility could be tested by repeating the radiographs
after a few minutes of positive pressure ventilation. It seems
obvious that studying radiographs in context – and knowing
what questions to ask during the visual search – helps students
to recognise relevant features, and to think of appropriate
differential diagnoses and patient management.
Therefore, when teaching radiographic interpretation, my aims
are to enable students to ask themselves simple questions
about the radiograph based on what they may know about the
patient or their initial observations of the radiograph, to use the
answers to these questions as a basis for forming hypotheses
that influence the direction of further searches for information,
and to try to build up an understanding of what diagnosis is
most likely based on the features that fit together. This approach
described in various veterinary textbooks [14]; however, there
is no convincing evidence that this approach is effective. For
example, medical students taught a highly structured, step-wise
approach to examining radiographs perform no better than
uncoached students. [15]
There are various potential problems with use of a directed
search pattern. Personally, I think it is unnatural and it seems
doubtful that anyone could optimally examine the periphery
of a radiograph while attempting to ignore an obvious feature.
This suspicion is supported by the results of studies using vision
tracking in which radiologists did not necessarily follow a
directed search even when they thought they were doing so. [13]
Furthermore, attempted use of a directed search pattern does
not eliminate the tendency to miss an unexpected peripheral or
subtle abnormality in a patient with an obvious abnormality, the
error known as “satisfaction of search.” [16] This error occurs
because presence of an obvious abnormality inevitably captures
visual attention and decreases the observer’s vigilance for more
subtle abnormalities. [17] A tendency to miss abnormalities can
occur because of incomplete visual search, but simply fixating
a feature on a radiograph does not necessarily mean it is
recognised. [18] Missed nodules often receive prolonged visual
attention, implying an active decision not to perceive a nodule.
[19] It appears that the majority of false negative errors result
from faulty decision-making rather than poor visual search.
[12,18] Faulty decision-making can only be exacerbated by an
approach to the radiograph that minimises use of the clinical
history.
82
Figure 5. Radiographs exist alongside a larger clinical context that
influences their use and their interpretation.
has been likened to a dialogue between the radiologist and the
radiograph. [20]
The hypothesis-driven search may be summarised as follows:
– Form a hypothesis about possible diagnoses on the basis of
history, experience or initial observation of film
– Use your hypothesis to prompt examination of specific parts
of the film (figure 4)
– Think of possible links between abnormalities
– Remember to check remaining areas of film last
Figure 6. Plot of sensitivity versus specificity to illustrate the effect
of clinical history (arrow) on diagnostic accuracy of radiography.
Sensitivity and, to a lesser extent, specificity increase when a
pertinent clinical history is available[25]. The area under the curve
is a measure of overall diagnostic accuracy.
This approach recognises that radiographs exist alongside a
larger clinical context (figure 5). With increasing experience, we
become more familiar with the usual location and appearance of
all the common veterinary conditions, which means we are more
likely to check specific locations on the film, chosen because of
our suspicions about that patient, rather than use a traditional
“periphery first” directed search pattern. In cases in which no
convincing abnormalities are found using a hypothesis-driven
search, it then makes sense to revert to a more directed search
pattern as a last resort before moving on to the next case.
The hypothesis driven search resembles the non-analytical
reasoning processes used by experienced radiologists (and expert
diagnosticians in other fields of medicine). [21,22] Introducing
students at an earlier stage of their training to the methods used
by most experts fosters consistency and may accelerate their
development. There is evidence that the most capable students of
radiology tend to use a hypothesis-driven search. In a study of 48
chiropractic students participating in a film reading examination,
the students who gained the highest score were better able to
identify key radiographic signs because they correlated the history
with the radiographic findings and thought of possible diagnoses
early in their examination of the films [23] (Table 1). Students who
adopted a flexible search pattern had significantly higher scores
than those using a directed search. [23]
The role of clinical history
There are assessments that present candidates with radiographs
without any accompanying patient information or history, but
this is an artificial situation. In practice, I suggest that we should
always know why we have made radiographs for the following
reasons:
– Knowing the history helps to answer key questions, e.g.
Is the study adequate?
What is the prior probability (prevalence) of disease?
– It affects our level of vigilance
– It helps to interpret a negative result
– Accuracy is increased when the history is available
The accuracy of interpretation of a variety of diagnostic tests
– including radiographs –increases when pertinent clinical
information is available. [21,24,25] This occurs as a result of
increased sensitivity and, to a lesser extent, increased specificity
(figure 6). In other words, knowing the history makes it more
likely that a radiologist will correctly observe an abnormality,
and less likely that they will over interpret a normal feature
of the films. Other studies have shown that prior information
significantly increased radiologists’ confidence, facilitates
new observations, and allows more specific diagnoses. When
interpreting a new set of radiographs of a patient that has been
examined repeatedly, viewing prior radiographs is more useful
than reading the written report. [26,27]
Table 1. Successful strategies for radiographic
interpretation [23]
• Use all available prompts
• Think of possible diagnoses early in examination of
radiograph
• Try to find the relationship between multiple
abnormalities
• Take your time
Caveat
There will always be radiographic abnormalities that are difficult
to recognise because they are inconspicuous. The conspicuity of
a radiographic lesion is defined as a ratio between lesion contrast
83
and surround complexity. [28] Conspicuity correlates well with
the probability of detecting faint nodular lesions in chest
radiographs [28], and this concept helps us to understand why
some abnormalities are liable to be missed even by experienced
radiologists. All we can do is try to be vigilant.
20.
References
22.
1.
23.
2.
3.
4.
5.
6.
7.
8.
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How to contact the FECAVA Office and
Secretary
Our Secretary is Laureline Ziwny
You can contact Laureline:
By phone : +32 (0)2 533 70 26
By e-mail : [email protected]
The times which you can speak to Laureline direct are:
Mondays to Thursdays from 9.30 am to 3.30 pm
The office is open from 8.30 am to 4.30 pm Monday to Friday
but outside Laureline’s hours you may get a member of the FVE
Secretariat
84
GENERAL FEATURE
FECAVA LECTURE
Dealing with MRSA in
Companion Animal Practice
D. H. Lloyd(1), A. K. Boag(1), A. Loeffler(1)
SUMMARY
Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide problem in human medicine that is now
increasingly recognised as a cause of disease in small animal practice. Molecular studies indicate that the majority of
isolates from dogs and cats are human hospital strains and point towards links with human healthcare institutions.
Treatment of MRSA infections relies on the same principles as the treatment of methicillin-susceptible S. aureus
(MSSA) and fortunately most UK MRSA isolates infecting pets are sensitive to co-trimoxazole and tetracyclines,
and to topical antimicrobials, including fusidic acid. MRSA can be carried by and exchanged between owners,
veterinary surgeons and in-contact pets, and is able to survive for long periods in the environment. This poses risks
to susceptible individuals. Decolonisation of both humans and animals can be attempted to reduce such risks but the
key to control of this organism lies in prevention of transmission. There is a need for rigorous hygiene procedures to
be instituted in veterinary practice to achieve this objective.
Key words: dog, cat, antimicrobial, resistance, MRSA
The origin and significance of MRSA
Staphylococcus aureus is a major cause of infection in both animals
and man. The advent of large scale production of the penicillins
in the 1940s, enabled S. aureus infections to be readily treated
and greatly decreased both morbidity and mortality caused by
staphylococci. However, resistance developed rapidly. At the end
of the decade penicillin-resistant strains predominated in many
hospitals. By 1950, 40% of all hospital S. aureus isolates were
penicillin resistant; and by 1960, this had risen to 80% [1].
worldwide problem in healthcare facilities and in 1983 dominant
epidemic clones (EMRSA) capable of affecting large numbers of
individuals within such institutions were described [2]. In the UK
two clones, EMRSA-15 and EMRSA-16 are now responsible for
more than 95% of hospital infections [3].
Resistance to methicillin and other β-lactam antibiotics in MRSA
is conferred by the mecA gene, which is part of a 21- to 60kb mobile genetic element, the staphylococcal chromosome
cassette, mec (SCCmec). Expression of mecA yields PBP 2A
which has a low affinity for β-lactam rings, the primary activesite of β-lactam antibiotics [4-6]. MRSA associated with hospital
infections commonly possess resistance to a wide variety of
antimicrobials, extending beyond the β-lactams (cephalosporins
and penicillins) and, in the more resistant isolates, including all
antibiotics in normal clinical use [7].
A worrying development in the MRSA story has been the
Staphylococcal resistance to penicillins is primarily mediated by
the production of β-lactamase enzymes and the β-lactamaseresistant antibiotics were developed to counter such resistance.
Methicillin (meticillin), one of the earliest of these, was
introduced in 1956 but by 1961 strains of S. aureus resistant
to this antibiotic (methicillin-resistant S. aureus, MRSA) were
already being recognised in continental Europe and in the
UK. MRSA spread rapidly. By the 1980s it was recognised as a
(1)Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hertfordshire GB-AL9
7TA .Corresponding author: David H. Lloyd E-mail: [email protected]
85
Dealing with MRSA in Companion Animal Practice - D. H. Lloyd
emergence of community-associated strains (CA-MRSA) causing
infection amongst young, healthy patients without significant
contact with health care institutions. CA-MRSA do not display
the multi-resistance of the healthcare-associated strains and
generally induce skin and soft tissue infections. However, they
can carry potent virulence factors leading to rapid, severe and
lethal infections [8]. This is an important difference from the
hospital-associated MRSA strains which do not show virulence
greater than the methicillin-sensitive S. aureus (MSSA) [9].
Risk factors for MRSA acquisition
in people
S. aureus, irrespective of its antimicrobial resistance pattern,
is thought to colonise the human nose in 30-70% of the
population [10]. Such commensal isolates are often involved in
human staphylococcal infections but cross-contamination from
other humans, animals or from the environment can also occur.
Factors predisposing people to MRSA acquisition, as compared
to methicillin-susceptible S. aureus, are well documented
in human medicine and include contact with carriers, age,
antimicrobial therapy, immunosuppression, chronic disease
and visits to healthcare facilities or nursing homes. In addition
to personal carriage of MRSA, risk factors for MRSA infection
are, for example, antimicrobial treatment (cephalosporins and
fluoroquinolones in particular), surgery and other invasive
procedures, staying at hospitals in countries with a high MRSA
prevalence and hospitalisation in intensive care units [11].
Fig 1: Pie chart showing the clinical presentations of 12 cases of
MRSA infection seen in five cats and seven dogs at a small animal
referral hospital in the UK between November 2003 and March
2004 (data of Boag, Loeffler and Lloyd 2004)[28]
was associated with surgical treatment, especially orthopaedic
surgery, but infection following trauma and in cases of recurrent
pyoderma was also seen. In the British Isles, two reports in 2004,
provided warning that MRSA infection was becoming a problem
in small animal practice. Rich and Roberts (2004) reported
isolation of 95 MRSA from specimens submitted to a veterinary
diagnostic laboratory during 2003 [26]. In March 2004, Boag
et al. (2004) reported an increase in cases of MRSA infection
seen at a small animal referral hospital [27]; 12 cases had been
confirmed in dogs and cats over the previous 5-months. Five
(42%) of these cases involved wounds or suture infections (Fig
1). Nasal swabs taken in five of these cases revealed concurrent
MRSA colonisation of the nasopharynx.
The correlation between the use of antimicrobials and selection
for drug resistant S. aureus is well documented [12, 13], and
healthcare-associated risk factors have also been explored in
detail in many countries. However, the extent of the risk for
MRSA acquisition in the healthy human community remains
controversial, partly because little information exists on MRSA
carriage rates amongst healthy people. Two small studies from
the UK and an extrapolation study from the US suggest that less
than 2% of healthy people are MRSA carriers [14, 15]. However,
higher rates of up to 10% are reported in medical staff and,
more recently, 10 to 20% carriage rates were found in veterinary
staff in Canada, the UK and Ireland [16-21].
A review of MRSA infection in dogs and cats in 2004 described
it as an emerging problem [28] and since 2000 there have been
increasing numbers of reports of MRSA in domestic animals,
including more than 30 published articles from the US, Canada,
Netherlands, Germany, Switzerland, the UK, Korea and Japan.
Most of these have dealt with infection and or carriage by dogs
and cats, although there is now a substantial number of reports
of infection in horses and other veterinary species including a
rabbit and a seal [21], and birds [29].
MRSA in dogs and cats
MRSA was first described in nasal isolates from two dogs by
Ojo (1972) in Nigeria [22]. However it was not recognised in
companion animals in Europe until 1988, when carriage by
a ward cat was associated with recurrent MRSA infections
amongst patients in contact with it [23]. Subsequently, in 1994,
recurrent infection amongst two healthcare workers was linked
to carriage of MRSA by their pet dog [24]. These reports provided
the first links between animal carriage and human infection.
Little is known of the actual rates of carriage of MRSA by dogs
and cats. Feline carriage was reported from Brazil in 1998,
where MRSA was isolated from the skin of 3 (2%) of 148
normal cats but not from the saliva of 150 normal cats [30, 31].
In 2005, Loeffler et al. reported oral or nasal carriage in 9%
of 45 dogs admitted to a small animal referral hospital [20].
However, a recent study failed to isolate MRSA amongst 200
dogs in Slovenia [32]. More detailed studies are now required to
define the MRSA carriage status and the factors which influence
such carriage amongst healthy pets.
Clinical infections with MRSA in dogs and cats have tended to
be associated with wounds and surgical procedures, as in man,
but cannot be differentiated clinically from infections caused by
Missa and S. intermedius. MRSA infection was first reported in
dogs in 1999 by Tomlin et al. who made a retrospective analysis
of 11 cases in North America and in the UK [25]. Infection
86
How do animals acquire MRSA?
There are already indications that self carriage and contact with
human MRSA carriers favour MRSA infection in pets. A recent
study has demonstrated that staphylococcal carriage isolates
and infection isolates are related in a high percentage of cases
[49] and that horses colonised with MRSA on admission to
hospital are 39 times more likely to develop MRSA infection
than controls [50]. In addition, preliminary results from a casecontrol study investigating risk factors in animals showed that
contact with a human MRSA carrier increases the risk that an
animal will acquire MRSA rather than MSSA by at least 6-fold
(Loeffler, data presented at the 1st International Conference on
MRSA in Animals, Liverpool, 20th June 2006). These findings,
together with the high MRSA carriage rates amongst pet owners
and veterinary staff, indicate that cross-contamination with
staphylococci between humans and animals plays an important
role not only during the close contact between pets and their
owners but also in the veterinary setting.
While S. intermedius remains the predominant organism
in staphylococcal infections and at carrier sites in dogs and
cats, the perceived increase in MRSA infections in companion
animals and the zoonotic implications of staphylococcal disease
have prompted extensive investigation into the origin of MRSA
isolated from animals.
It is well documented that staphylococci, including S. intermedius
and S. aureus (both resistant and susceptible to methicillin) can
be transferred between humans and animals in both directions
[33-36]. Furthermore, typing studies from several countries
have shown that MRSA isolates from dogs and cats are identical
with or closely related to the human epidemic hospital-acquired
MRSA important in those countries [19-21, 25, 37-40]. This
strongly suggests that the principal source for MRSA infection
in pets is contact with humans infected with or carrying MRSA.
When to suspect MRSA infection?
On the other hand, a few reports have also identified MRSA
isolates from infected and healthy animals that are genetically
distinct from human epidemic clones [41, 42]. This raises concern
about animal-specific MRSA isolates developing, which may
be particularly well adapted to animals and constitute another
reservoir for human infection. As the mecA gene, which can
confer broad resistance to methicillin, has also been identified in
other staphylococcal species commonly found in animals, gene
transfer between staphylococci on animals may also occur [4346].
MRSA infections cannot be recognised from their clinical
presentations alone. They resemble those of infections with
methicillin-susceptible S. aureus and S. intermedius and helpful
MRSA specific features have not been identified for dogs and
cats (Loeffler, data presented at the 1st International Conference
on MRSA in Animals, Liverpool, 20th June 2006, [51]. In general
though, MRSA should be suspected 1) in post-operative and
traumatic wound infections, 2) in skin and soft-tissue infections
unresponsive to antimicrobial therapy and 3) in cases with a
previous history of MRSA infection or where a zoonotic risk of
MRSA infection has been identified. See Table 1.
As MRSA can survive on dry surfaces for many months,[47]indirect
transfer and acquisition of this organism from the pet’s
environment is also possible. Only a few studies have so far
investigated the presence of MRSA in the veterinary environment
revealing survival on up to 10% of sampled surfaces [20, 37,
48].
Thus, diagnosis of MRSA infection is based on clinical signs
consistent with bacterial infection, ideally supported by
cytological evidence of cocci and inflammatory cells from
material collected from the site of infection, together with
isolation of MRSA by microbiological tests on submitted clinical
material.
While the sources of animal infection have been studied
extensively, the circumstances which facilitate transmission
from humans to pets have not been investigated. It may be
hypothesised that risk factors for MRSA infection in animals
are similar to those known in humans such as contact with
human or animal MRSA carriers, self MRSA-carriage, previous
antimicrobial and immunosuppressive therapy, chronic disease
and invasive veterinary procedures (such as surgery and implants).
Sampling and laboratory submission
Sample collection for bacterial isolation will be aimed at
collecting material most likely to yield the relevant pathogen.
The sampling methods will depend on the site of infection
but will not differ from those performed to investigate other
bacterial infections. For example, a swab submitted in bacterial
transport medium can be taken from a pustule or an ulcerated
skin lesion while biopsy specimens in plain sample pots with a
few drops of sterile saline or blood collected in blood culture
vials may be required for deep tissue infections or in cases of
suspected bacteraemia, respectively. Antimicrobial therapy
should be discontinued prior to sampling to improve recovery
of bacterial organisms. In such cases, cytological examination of
material from infection sites may indicate whether bacteria are
likely to be grown from samples. In addition, the clinician must
assess whether discontinuation of therapy would be appropriate
for the individual patient in the face of possible bacterial coinfections.
Table 1: When to suspect MRSA infection in a pet.
When to suspect MRSA infection?
Post-operative and traumatic wound infections (non-healing
wounds)
Implant infections (e.g. catheters, orthopaedic implants)
Unresponsive skin and soft tissue infections
Previous history of MRSA infection
Known owner infection or carriage
Cluster of MRSA infections recently diagnosed in the clinic
87
Occasionally, sampling for MRSA carriage at mucosal sites is
indicated, for example to assess the risk for re-infection with
this organism in animals susceptible to recurrent infections.
Examples would be those suffering from allergic skin disease
or those receiving immunosuppressive therapy, where surgical
implants need to be kept in place or when owners raise concern
about zoonotic transfer [35, 36]. Mucosal sites such as the distal
part of the nares, the buccal mucosae and the perineum have
been shown to yield staphylococci readily in carrier animals, and
moistening the swab with sterile saline prior to sampling may
aid recovery of bacteria [20, 52].
In vitro susceptibility testing for antimicrobials for clinical
purposes is based either on disc diffusion tests with fixed cut
off values designed to predict resistance in vivo or by estimation
of minimum inhibitory concentrations of the antimicrobials by
manual or automated methods. Phenotypic methicillin resistance
can either be determined by disc diffusion tests using methicillin
or its representatives oxacillin and cefoxitin [63]. Alternatively,
the use of selective agar plates containing oxacillin and a colourindicator can shorten the time to identification of MRSA but at
additional expense. In a small proportion of S. aureus isolates
with phenotypic resistance to methicillin and other β-lactam
antibiotics, resistance has been due to an excessive production
of penicillinase, rather than an altered penicillin-binding protein
as in the epidemic MRSA isolates.
Sampling of environmental sites may sometimes be performed
for example to monitor implementation of infection control
measures or to identify problem areas in the clinic. To improve
the bacterial yield, swabs can again be moistened with sterile
saline prior to sampling [20].
In addition to species identification, the definition of S. aureus
isolates with phenotypic methicillin resistance as MRSA requires
demonstration of the mecA gene, most commonly by PCR
based methods. If expressed, this gene confers resistance to all
penicillins and cephalosporins [64].
Swabs, tissue or fluids are typically submitted to diagnostic
veterinary laboratories together with the signalment of the
animal, a brief summary of the suspected bacterial infection,
sampling site and a request for bacterial culture and antimicrobial
susceptibility testing. In an animal with known or suspected
MRSA infection or when specifically investigating MRSA carriage
or environmental contamination with MRSA, this should be
indicated on the submission form. It will enable the laboratory to
choose enrichment methods to increase the yield of staphylococci
and it may accelerate the bacteriological diagnosis as MRSAselective media can be used at an early stage.
S. aureus has been shown to be highly clonal and typing of
isolates of interest can provide valuable epidemiological data,
such as for example identification of related isolates within an
outbreak [65, 66]. Typing of clinical isolates, however, is unlikely
to be of benefit for the management of the individual case.
Treatment of infection
The clinical manifestations of MRSA infection in animals are
very variable; hence there is no treatment protocol which will
be suitable for all patients. In human medicine, MRSA infections
range from relatively benign superficial skin or wound infections
through to life threatening bacteraemia with the development
of septic shock [67]. Although the majority of reports in the
veterinary literature describe patients with skin or post-operative
infections [21, 25, 68], more serious systemic infections can
occur. As with all infections, the treatment must be tailored to
the individual patient.
Laboratory identification of MRSA
Staphylococci are initially identified by colony morphology as
white or yellow, round, shiny and smooth colonies on blood
agar. Additional criteria such as haemolysis, the ability to clot
plasma (coagulase tests) and a number of other biochemical
tests help to categorise them broadly into coagulase-negative
staphylococci and the more commonly pathogenic coagulasepositive staphylococci, and to distinguish staphylococcal species.
However, as morphological and biochemical characteristics
vary even within a species, no single test exists to differentiate
for example, S. intermedius and S. aureus, and a combination
of several test results is required for reliable identification.
While various molecular techniques are available to distinguish
staphylococcal species based on species-specific sequences in
highly preserved genomic regions [53-56], speciation in busy
diagnostic laboratories with a high throughput of clinical samples
is often based on results from automated bacterial speciation
systems (e.g. Vitek or Microscan Walkway). These can perform
a battery of biochemical tests in a short time [57]. Owing to
such difficulties in bacterial speciation, MRSA may occasionally
be misidentified as multi-resistant S. intermedius or the latter
may mimic MRSA [58]. For example, an isolate reported as S.
intermedius resistant to cefalexin is more likely to be S. aureus
and perhaps an MRSA as resistance to cephalosporins has been
extremely rare in S. intermedius so far [59-62]. In such cases,
a critical evaluation of the report by the clinician together with
the patient’s history should prompt liaison with the laboratory
to discuss unusual or unexpected results.
When deciding on a treatment plan, consideration should be
given to:
– the antibiotic sensitivity profile of the MRSA isolated from
that patient
– the severity of the infection and, particularly, whether the
patient exhibits any systemic signs (fever, leucocytosis)
– the patient’s underlying disease or any co-morbid
conditions.
In some cases of superficial wound infection in systemically
well animals, diligent local wound management according to
basic principles will result in resolution of infection without
the need for systemic antibiosis. If the infection is associated
with an implant (e.g. external skeletal fixator pin), removal of
the implant, at the earliest possible opportunity, will also aid
resolution.
However, in many patients antibiotic therapy is required. This
includes patients with systemic evidence of infection and patients
88
where MRSA infection has occurred secondary to a predisposing
condition (e.g. chronic urinary retention, chronic atopy). The
antibiotic used should be chosen based on culture and sensitivity
results; knowledge of the sensitivity pattern of the strain(s) of
MRSA that are prevalent in the geographical area can help with
empirical antibiotic choice whilst awaiting microbiological results.
Although MRSA generally shows resistance to commonly used
agents, most are sensitive to some classes of antimicrobial. In the
UK, most infections in companion animals have been with MRSA
sensitive to tetracycline and co-trimoxazole, with some showing
sensitivity to the fluoroquinolones. Sensitivity to the topical
antimicrobials, fusidic acid and mupirocin, is also commonly
demonstrated. Recent guidelines for treatment of MRSA in the
human population in the UK suggest that tetracyclines should
be considered for the treatment of human patients with skin,
soft tissue and urinary tract infections where there is a low risk
of bacteraemia [69]. Similar guidelines do not exist for veterinary
species but both tetracyclines and sulphonamides are licensed
for use in veterinary species and are often a first line choice.
Exposure to fluoroquinolones has been identified as a risk factor
for infection with multi drug resistant bacteria of several species
and they should be used with caution.
et al. (2006) conclude that there is sufficient evidence to
support the continuing use of such procedures although more
experimental evidence is required [71].
Rarely patients may develop MRSA sepsis. These critically ill
patients require intensive management with monitoring and
support of all vital organ systems. Antimicrobial therapy for
these patients is challenging as MRSA is generally not sensitive to
any of the intravenous bactericidal agents (e.g. aminoglycosides,
β-lactam derivatives, cephalosporins) that would usually be
chosen. Vancomycin is the current drug of choice in the human
field [69] and has been used experimentally in dogs [70]. Clinical
experience with vancomycin in small animal patients is however
scarce. The expense of the drug and the recognition in human
medicine of MRSA isolates with poor sensitivity to vancomycin
may limit its application in the field of companion animal
medicine.
Other than patients with sepsis, the prognosis for animals with
MRSA infection is generally good with appropriate treatment.
Dependent on the underlying condition, decolonisation may
also be considered as part of the treatment regime.
Limited clinical experience with decolonisation (Lloyd, personal
observations) suggests that treatment of canine mucosal sites
with 1% fucidic acid for two weeks coupled with the use of
antimicrobial shampoos and systemic antimicrobial therapy is
effective in removing MRSA but duration of decolonisation is
not known. In principal, treatment of carrier animals should
be started as soon as the chance of re-infection has reduced,
e.g. once a wound has healed, skin lesions have resolved and
implants, e.g. catheters, have been removed. Decolonisation
can also be applied to carriers that have not been infected but
present a risk to other animals or to humans in contact with
them.
No published data on decolonisation of MRSA carriers is
available for pets but studies on decolonisation of dogs with
S. intermedius was reported by Saijonmaa-Koulumies, Parsons
and Lloyd in 1998 [52]. In this study normal laboratory beagles
were treated at the nares, conjunctivae, anus and vulva with
topical 1% fusidic acid twice daily for seven days; skin and the
environment remained untreated. The frequency and populations
of pathogenic staphylococci decreased significantly after therapy
and were still reduced after three weeks. However populations
returned to their original levels after three weeks. The authors
concluded that the effect of mucosal treatment on cutaneous
populations of S. intermedius indicated the importance of the
mucosae as the carriage sites for these organisms. It might
be expected that such treatment would have a similar effect
on MRSA colonisation of dogs. In addition, as S. intermedius
adheres to canine keratinocytes more readily that S. aureus
[75] it is possible that, following decolonisation with S. aureus,
recolonisation with S. intermedius may occur.
Prevention of spread
Although the prevalence of MRSA carriage and infection appear
to be increasing in small animal patients, the level of infection
is much lower than that seen in the human healthcare system
in many European countries. The veterinary profession can
learn from experience in the human field with action at this
early stage to prevent MRSA becoming endemic within our
clinics and patient populations. Each practice should develop a
policy for dealing with MRSA positive patients. Rational control
measures should be based on the available evidence from the
human infection control field coupled with knowledge of MRSA
epidemiology as it relates specifically to veterinary patients.
Further information and up-to-date guidelines may be found
on the BSAVA website at www.bsava.com/resources/mrsa/
mrsaguidelines/mrsaguidelines.htm
Decolonisation
Decolonisation involves the use of antimicrobials to remove
MRSA from colonisation sites. In man, this generally involves
treatment of the nasal mucosa with a topical antimicrobial agent
to which the colonising strains are sensitive, such as mupirocin
ointment, together with the use of antimicrobial washes and,
in some cases, systemic antimicrobials [71] and environmental
cleansing. Higher success rates are achieved with patients in
a hospital setting when all these methods are combined [72].
Topical treatment of healthy healthcare workers with intranasal
mupirocin ointment twice daily for five days was associated
with a 91% reduction in the prevalence of S. aureus carriage.
However, recolonisation occurred in 26% of decolonized
healthcare workers within four weeks [73]. The feasibility of
routine MRSA decolonisation in humans is still in question [74]
but in a major review of interventions for the prevention and
control of methicillin-resistant Staphylococcus aureus, Loveday
Debate still exists within the human medical literature as to
the most appropriate control measures [72, 76]. Transmission
between patients on the hands of health care workers seems to
be the major mode of spread but the role of the environment
should not be overlooked [77]. In humans, prior colonisation
with MRSA is also recognised as a significant risk factor for
89
Fig 2a: Bank of kennels in a veterinary intensive care unit showing
alcohol hand rub bottles attached to each of the kennel doors.
Fig 2b: Close up of an alcohol hand rub bottle on a kennel door.
Convenient placing of the hand rub bottle promotes diligent hand
hygiene.
subsequent infection, with active surveillance cultures and
decolonisation being recommended in high risk human patients
[72, 76].
measures are most effective is lacking in the veterinary field.
Interpretation of evidence from the human literature is difficult
as multiple control measures are often used simultaneously [76].
However, barrier nursing procedures including use of gloves,
plastic aprons, shoe covers and face masks are recommended
whenever handling the patient to reduce the risk of contamination
of the veterinary staff (Fig. 3). Rigorous hand washing measures
should be enforced before and after every patient contact.
Procedures on MRSA positive patients should be performed
at the end of the working day whenever possible. Adequate
staffing should be provided; heavy nursing workload has been
identified as a consistent risk factor for MRSA transmission in
many human studies [81-83].
Currently it seems that most MRSA infections in veterinary
patients are with human epidemic strains of MRSA however the
immediate source of the infection is rarely identifiable. Veterinary
staff may be at higher risk of being colonised than the general
population (Hanselman, data presented at the 1st International
Conference on MRSA in animals, Liverpool, 20th June 2006) [20]
with the potential for transmission to their patients. However,
the infection could also originate from other in-contact humans
(especially owners who may have close physical contact with
their pets) or the environment. Owners of MRSA positive pets
should seek medical advice from their general practitioners if
they are concerned and especially if they have any chronic health
problems themselves. It is also unknown how many healthy dogs
and cats are colonised with MRSA with possible auto-infection
or transmission to other patients if they are hospitalised.
The role of screening of patients and veterinary staff in the
control of MRSA in the veterinary field is unclear. Identification
and subsequent decolonisation of MRSA colonised or carrier
animals may help to reduce the infection rate but screening of
all veterinary patients is unlikely to be practical or cost-effective.
Future recognition of risk factors for MRSA colonisation in pets
will help us to target screening to patients most at risk of being
colonised. Although veterinary staff may be at increased risk
of being colonised, identification of a colonised staff member
does not necessarily mean that that person has acted as a
source for infection. Screening of veterinary staff should be
undertaken with caution and careful thought must be given
to confidentiality and liability issues. Consideration should also
be given to the procedure for any staff members identified as
being MRSA positive. Routine screening of veterinary staff is not
recommended; in the face of an outbreak, staff screening may
be part of the control plan but advice should be sought from a
person experienced in infection control.
Considering the wide range of possible sources, broad based
and rigorous infection control measures should be used at all
times. Many of these measures will also be of benefit in the
control of other bacterial pathogens. Hands and equipment
should be cleaned between every patient contact. Evidence
from the human field suggests 100% compliance with hand
washing is unlikely to occur. Compliance rate may be improved
by the use of alcohol based hand rubs alongside traditional hand
washing (Figs. 2a and 2b) [78, 79]. The environment should be
cleaned with a focus on the critical “hand touch” sites; sites that
are in close proximity to the patient that are frequently touched
by staff between hand washing and patient contact (e.g. kennel
doors, infusion pumps). Regular audit of environmental cleaning
should be carried out [80].
The role of inappropriate antibiotic usage in the spread of
antimicrobial resistance must also be considered. Exposure
to broad spectrum antibiosis (notably third generation
cephalosporins and fluoroquinolones) has been associated with
an increased risk of MRSA infection in several studies [84, 85].
Practices should consider auditing antimicrobial usage and take
When a patient with MRSA is identified, contact with staff and
other patients should be minimised. Physical isolation of the
patient should be performed wherever possible to reduce the
risk of cross-transmission. Objective evidence as to which control
90
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91
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93
GENERAL FEATURE
COMMISSIONED PAPER
Pet Euthanasia helping clients through it
G. Gadd (1)
INTRODUCTION
For many of us in practice Euthanasia is a daily occurrence and a necessary part of our everyday work. For the owner
this procedure which we regard as routine may be the end of a relationship spanning many years with many shared
experiences and the loss of a treasured companion or an only friend.
Every euthanasia is unique. In order to support our clients through their bereavement we must show empathy and a
positive regard for their values and feelings.
It can be helpful to first gain an impression of the type and strength of the bond between client and pet in order to
prepare for the type of grief they may experience and plan the extent of the support they may need. However, we
must not be too quick to pre-judge and should always be open to a changing situation, led by the client.
– Keeping the pet alive is causing anguish to the owner, and
causing a stressful environment
– The owner is unable to afford treatment or special care
This paper was commissioned by FECAVA
for publication in EJCAP
In all these cases owners will be able to make balanced
judgements and will usually know when the right time for
euthanasia has come. The most important thing for a supporter
to do at this stage is reassure them that their reasons are
understandable and valid.
Euthanasia may be appropriate if the current situation is causing
extreme anguish as pets tend to be sensitive to their owner’s
state of mind. Permanent upset for the owner can also cause
constant stress for the pet.
Understanding the owner’s reasons
Bereavement support begins with the initial phone call to the
receptionist who should be sensitive and practical, ensuring
that clinical staff are prepared for a potential euthanasia. Most
cases involve pets in advanced old age where clients have been
anticipating, and often hoping for, a natural and peaceful end
but have come to realise the time is right to intervene.
Some of the most common reasons presented by owners for
their pet’s euthanasia include:
– Advanced old age
– Chronic, incurable disease
– Behavioural problems linked to senility
– Inability to exercise/feed
– Loss of toilet training/incontinence
– Pet not fit enough to cope with house move/emigration
– Animal shows severe aggression which cannot be controlled
Preparing clients
The responsibility of the veterinary profession when facing the
euthanasia of a pet is to balance the welfare of the animal and
the needs of the owner.
Although the responsibility of the decision ultimately rests with
the owner, the vet’s opinion obviously has great influence.
In order to make the decision of prolonging life or opting
for euthanasia the owner will be helped by considering the
following:
– The animal’s character and its will to live.
– Physically, is the pet able to:
• Move around unaided?
• Go outside to exercise and urinate/defecate?
Often the decision to euthanase is taken because the owner is
unable to continue caring for their pet for one of the following
reasons:
– The owners themselves are old or disabled and unable to care
for their pet
(1) Gill Gadd VN.MBVNA Castle Vets Healthcare Centre, I Tilehurst Road, Reading , Berks,
GB -RG1 7TW E-mail : [email protected]
The author is an experienced qualified Veterinary Nurse. She specialises in bereavement support work and has completed the Open College Network’s
accredited course “Offering Support in Pet Bereavement” at level 3. She also holds a certificate in counselling from CRUSE Bereavement Care and works
for them as a bereavement volunteer.
95
Pet Euthanasia - helping clients through it - G. Gadd
and act on it.
The bereaved client needs:
– Clear, succinct information and the freedom to make their
own choices/decisions
– Respect and empathy showing a true recognition of their
grief
– Time to say goodbye and time to work through the transitional
stages of grief
Each practice could well design a model to furnish those needs
through training, communication and the allocation of time for
bereavement situations.
The pre-euthanasia discussion
The pre-euthanasia discussion allows the client to take in relevant
information whilst in a relatively unemotional state. After the
event they can become overwhelmed by grief and have a feeling
of unreality, making it impossible to process details or make
important decisions.
In order to further help a client to decide on the best course
of action for their sick or injured pet, the following may be
discussed:
– Possible treatments/surgical options listing clear and real
chances of recovery/prolonging life/improving quality of life.
(It is very difficult to give an estimate of life expectancy and
this should not be attempted).
– Information about the process of euthanasia, what it will
mean for the pet and, more importantly, what it will mean to
the client - how their life will be affected and how stages of
grief may mean coping with strong emotions.
– Information on how other cases have worked out - what you
have seen in practice and a fair and truthful assessment of the
prognosis.
Gill Gadd with Chloe
– Rest peacefully without anxiety, distress or pain?
Also:
– Are bad days increasing and outnumbering the good ones
and is the animal suffering physically or mentally?
– Does the animal feel pain which cannot be satisfactorily
alleviated?
The owner also needs to consider their own ability to cope with
their animal however well intentioned they may be.
– Can they cope physically with the demands of nursing care?
– Is the financial cost of the care going to be, or become, a
problem?
– Are they able to cope emotionally with the pet’s demise whilst
they are undertaking the responsibility of its care, and do they
have the support of relatives, friends and practice staff?
Clients need careful handling and support at this time and an
interview in which they are encouraged to make plans and
prepare for dealing with the euthanasia can be very helpful in
the long term.
As a supporter we need to establish a history of the case and
the basis for the decision to euthanase. We can then offer advice
and information on the practical care needed, the animal’s
quality of life and the option of euthanasia and what it may
mean to the client.
Ultimately, it is the client who decides, for whatever reason, the
fate of their own animal. In most cases clients do have their
pet’s best interests at heart and, even if euthanasia must be
brought forward because of the owner’s inability to cope, that
animal will at least benefit from continuity at the end and will
not suffer distress.
We have at our disposal the means to deliver this “gentle death”
and need only the skill to help the clients through this difficult
and emotional time. They are better supported by a positive
attitude to their decision and it is up to us to understand their
reasons and not pre-judge or condemn them.
The client’s emotional needs
Owners and their pets are reassured when the staff involved are
familiar. Maintaining a continuity of care will be beneficial when
helping them to come to terms with the diagnosis, preparing
for the death and during the final moments, as well as during
stages of aftercare and support.
One to one support using basic counselling skills can be
performed effectively by nursing and ancillary staff who are
often without the same time constraints as veterinary surgeons.
Some members of staff will be better suited to a counselling
role. We can all however acquire and improve on the necessary
skills, not only of imparting information but also facilitating its
understanding and supporting the recipient while they accept
It should always be made clear to the client exactly what is going
to happen during the process of euthanasia. This allows the
client to remain in control of the situation so that they do not
feel that the vet has “taken over” or is likely to do something
unexpected. Feeling in control can lessen anxiety and help the
client to accept the responsibility and the consequences of the
final decision they have made on their pet’s behalf.
It is also useful to include a warning of possible problems, such
as failure to locate a viable vein, so that the owner does not
assume that the vet has been incompetent or that a situation
96
such as this, should it arise, is unforeseen.
The client should also be prepared for disturbing reflexes
which they may witness as these can lead to anxieties and
misunderstandings. Having some idea of the process and
possible problems can help ensure that any “surprises” are
avoided. Discussing options for the disposal of the pet’s body
before euthanasia is advisable as the owner is more likely to be
able to state their preference with some objectivity. If they have
not already decided on the option, it is much easier to discuss
this before the event whilst the owner can still think clearly.
times. Clients can be spared the upsetting trauma of being
seated with others in the waiting room if they are conducted
straight through to the consulting or farewell room on arrival.
It is also helpful to allow them to leave through a back door or
staff exit.
Longer appointments can be made with a nurse involved around
the vet’s consultation slot to offer clients more time and privacy
before and after the euthanasia. This eases time considerations
for the vet, provides extra care for the client and enhances job
satisfaction for the nurse.
Organising a practice protocol
With an animal of ill- temperament or one that is in a great deal of
pain and may resent appropriate restraint, it may be advisable to
give a sedative such as Medetomidine Hydrochloride (Domitor®Pfizer) prior to the final injection to ease the procedure.
Alternatively, Acepromazine in an oral form can be dispensed
for administration one hour before arrival at the surgery. Results
can however, be unreliable with excitable animals showing little
response.
The most important factors for managing euthanasia in the
surgery from a client’s point of view are a caring and helpful
approach and making time for them, their animals and the
procedure. It is important too, that everything behind the scenes
such as printing consent forms and the booking of appointments
goes smoothly. This shows the practice in a good professional
light and ensures that the veterinary team’s attention is not
distracted from the empathy and care they show the client.
In non-aggressive animals, the placement of an IV catheter prior
to the euthanasia allows the owner to hold and cuddle their pet
whilst the vet can inject unaided. Although this involves taking
the pet away from the owner for a short time on arrival, clients
rarely object and it can ease the whole procedure, making the
final moments less stressful for all involved.
Finally, allow the owners time to say goodbye to their pet and
offer to briefly leave the room. Don’t be afraid to encourage
them to talk about the life of their animal, and be prepared to
Pre-euthanasia clinics should be scheduled with owners to help
the final procedure to run more smoothly. A pre-euthanasia talk
with a VN can summarise the procedure and alert the client to
available options regarding disposal of the body.
For these clinics to have a chance of succeeding they must be
recommended to owners by the vets whilst in consult with
geriatric or terminally ill patients.
Another source of information can be provided in the form of
a practice leaflet, outlining the euthanasia procedure and the
available options.
The farewell room should be designed to create a more natural,
homely setting
Privacy and comfort will ease the stress of the situation and it is
worthwhile considering setting aside a room within the practice
designed to create a more natural, homely setting. Remove the
computer to ensure total focus on the individual. Avoid having
an examination table, which will serve to form a barrier; instead
arrange same level seating. To further create an atmosphere
of calm for animal and owners, the following features may be
included:
– Upholstered chairs (with removable covers) to provide more
comfortable seating
– A low wooden coffee table on which deceased pets can be
laid
– A standard lamp for ambient lighting (strip lighting still
functional when needed)
– A sideboard/cupboard to house the range of caskets available
for ashes
– A book of condolence which helps owners to feel their grief
is “normal”
– Framed pictures should replace posters and flowers/plants
help make the atmosphere less clinical
– A large floor rug which can be lifted for cleaning
– Leaflets, books and cards from clients
If your practice does not have the extra space for this luxury,
consider using the consulting room in the quietest location, or
schedule your euthanasia appointments outside busy consulting
97
Pet Euthanasia - helping clients through it - G. Gadd
themselves may have been too embarrassed to put forward. A
handout listing useful telephone numbers and advice on outside
support available can be immensely helpful.
There is a wealth of literature available from organisations and
charities to help clients come to terms with their grief and the
overpowering emotions they may be encountering.
The Blue Cross (www.bluecross.org.uk) run their own
telephone help-line for bereaved pet owners, staffed by trained
volunteers.
EASE, The Environmental Animal Sanctuary and Education
services and also run a Pet Bereavement Support Service are
on-line at www.ease-animals.org.uk
CRUSE Bereavement Care (www.crusebereavementcare.org.
uk) is a voluntarily run organisation and will help in cases of
complicated loss where grief involves previous bereavements.
A sideboard/cupboard to house the range of caskets available for ashes
The key to a successful euthanasia is forward planning. If we
can get the client to think about when, why and where, with an
idea of their option for body disposal when they know the time
is approaching, then all can be made ready and someone can
be on hand to be with them with support throughout. All this
planning can include the last thing anyone wants to think about,
the payment. Pre-payment can be arranged or it can be agreed
that an invoice be sent after the event. Either way, all concerned
know what to expect without having to talk it through at length
on the day.
Each case we see is different; how many clients, who could really
benefit from this close, personal service, are slipping through
the net; not having the chance to spend time with the support
of a nurse, hurried through an ordinary consultation and sent
home with an empty blanket wondering if there is someone
they could talk to?
Veterinary practices should be aiming to
achieve a working protocol to care for as
many clients, in the way that is right for
them, as possible.
listen to stories of the relationship, as this shows empathy and
understanding and is always much appreciated.
Many well-written leaflets are available from The Blue Cross and
other charities to help owners work through and understand
the grieving process and it can help to have these to hand as
the client leaves. The Pet Bereavement Support Service runs a
telephone helpline staffed by volunteers and this service can be
of great help.
Handwritten cards of condolence may be sent but always
make sure they go under separate cover from any invoice that
is due. A follow up telephone call shows the client that their
links with the practice have a genuine value. Your empathy with
and concern for them at this time will be truly appreciated and
remembered. Try to offer this continuing support by mentioning
at the euthanasia consultation that you or
members of your bereavement support
staff are willing to make or receive calls if it
is felt that the client would appreciate this.
Consider also using e-mail as another point
of contact for grieving clients.
Many people do not realise how deeply
BEREAVEMENT
the bereavement will affect them and the
influence it may have on aspects of their
everyday lives, and often have no one to
turn to when the loss becomes tangible.
Our continued concern may not directly
bring in revenue but has a positive long term
effect in engendering goodwill by word of
mouth. Clients are more likely to become
permanently bonded to the practice.
pet
External Sources of
Support
Staff should be aware of their limitations
and referral to trained counsellors or
medical professionals may be neccessary
in some cases. Suggesting to a deeply
distressed owner that it is possible for
them to speak with their doctor or with
the Samaritans will show you understand
their emotions and raise issues that they
S U P P O R T
Useful contacts and
further reading
Companion Animal Death Mary Stewart
(Butterworth Heinemann)
The Human-Animal Bond and Grief Lagoni
Butler Hetts (Saunders)
Counselling Skills for Health Professionals
Philip Burnard (Nelson Thornes)
Details of the study course Offering
Support in Pet Bereavement can be
obtained form The Blue Cross, Shilton
Road, Burford, Oxon. OX18 4PF or online
at www.bluecross.org.uk
L I N E
0800 096 6606
E M A I L
S U P P O R T
[email protected]
98
The Blue Cross run their own telephone
help-line for bereaved owners.
BOOK REVIEWS
Rapid Interpretation of heart
and lung sounds
A guide to cardiac and respiratory
auscultation on dogs and cats
Francis W.K. Smith, Bruce W. Keene and
Larry Patrick Tilley
Published by Published by Elsevier Saunders (http://intl.elsevierhealth.com/vet)
Hardback ISBN 07121604269
€ 44.99 £ 29.99
ferent auscultatory phenomena, making
the book very useful as a handbook to be
used in day-to-day practice. In summary,
this book and CD are excellent tools to
help learn the difficult art of auscultation
and is useful for the veterinary student as
well as the experienced clinician.
Anna Tidholm, DVM, PhD, Dipl. ECVIM (S)
Small Animal Dermatology
A Colour Atlas and Therapeutic
Guide – Second Edition
Linda Medleau, Keith A. Hnilica
Published by Published by Elsevier Saunders (http://intl.elsevierhealth.com/vet)
544 pages 1364 illustrations Hardback
ISBN 0721628257€115 £ 76 99
This book of approximately 100 pages,
together with a audio CD, is an excellent
guide to heart and lung sounds. The book
is very thorough and complete and at the
same time small enough to fit into a (fairly
large) pocket. It is written by three experts
in the field of cardiac and respiratory auscultation. The book provides step-by-step
instructions on how to identify, interpret
and differentiate normal heart and lung
sounds, abnormal heart and lung sounds,
murmurs and arrhythmias. Complete with
pre as well as post reading ‘test’, the book
and CD will tell you how much of different
heart and lung sounds you already knew
before entering the “course” and how
much you have learned from reading the
book and listening to the CD. The book is
divided into four chapters as follows: Heart
sounds, Murmurs, Arrhythmias, and Lung
sounds. Each chapter begins with clearly
stated objectives followed by a pre-test to
evaluate your level of knowledge beforehand. After reading the text and listening
to the CD there is an appropriate post-test
to evaluate what you have learned. Both
simulated sounds and natural sounds
from clinical cases are presented on the
CD. Simulated sounds allow the listener
to focus on heart sounds without the distraction of breathing sounds and artifacts.
Natural sounds of murmurs and abnormal
respiration are included to represent the
clinical situation. Graphic presentations of
ECG’s and phonocardiograms accompany
the heart sounds for clarity. This appears
to be a very efficient way of conveying
knowledge to the reader. Each chapter
is also equipped with tables for a quick
reference of differential diagnoses for dif-
Not having been aware of the First Edition of this book, I have been delighted to
find such a useful addition to the library of
Dermatology texts. The authors declared
intent with the first edition was to create
a colour atlas to complement Muller &
Kirk’s Small Animal Dermatology. This volume, however, far exceeds this aspiration.
The book provides an excellent diagnostic
reference for all veterinarians dealing with
the multitude of small animal skin cases
presenting daily in first opinion clinics. The
authors’ logical approach in providing an
initial listing of differential diagnoses that
should be considered from the presenting symptoms is accompanied by useful
diagnostic algorithms for both canine and
feline pruritus. Unfortunately, similar algorithms are not provided for non-pruritic
conditions and these would have been a
welcome addition. The second chapter
provides clear, well illustrated instructions
for diagnostic techniques which are often
under used by first opinion clinicians.
Chapters 3-12 cover the various clinical
entities met in small animal dermatology, from the very common; abscesses,
pyoderma and atopy, to the more rare
presentations such as cryptococcosis,
toxic epidermal necrolysis and hepatocutaneous syndrome. Each condition is
well described and its differentials listed
99
along with guides to diagnostic confirmation, treatment options and prognoses. A
greater emphasis on the incidence of each
condition may be helpful to the less experienced clinician. This is a minor point
however and will vary from country to
country. Common synonyms are given for
each condition and tables of treatment
options are helpfully provided in those
conditions such as Pemphigus, where alternative or combination treatments are
often required. Chapters 13-16 cover miscellaneous conditions, an excellent piece
on tumours and the specific conditions related to Eyes, Claws, Anal Sacs and Ears. A
final chapter showing pre- and post-treatment images is interesting, if a little less
informative, and, as the pre treatment images are taken from the individual specific
disease sections, cross references from
these sections to the post-treatment images would have been welcome.
Four appendices provide a useful listing of
available topical shampoos, topical therapeutics, otic preparations and systemic
therapeutic drugs, though all references
are, of necessity, to products available on
the American market. The detail of how
products are supplied is also only applicable to the home market. Each chapter
relating to a disease group is closed by listing suggested current readings with references. These often refer to narrow areas
of specialist interest rather than directing
readers to broader subject summaries,
which may be more helpful to practitioners.
The outstanding feature of this book is
the wonderful clinical photographs and
their impressive reproduction. The authors
are to be congratulated on their comprehensive coverage and superb clarity, often
showing multiple views of lesions. The
colour reproduction is rarely less than
excellent throughout all of the 1200+ images provided.
I would highly recommend this book to
every clinician working in small animal
practice as an excellent reference on all
aspects of veterinary dermatology. It is a
work of significant value, either as a stand
alone reference text or, as originally intended, as the perfect companion to the
standard dermatology texts. I’m sure it
will be in constant use by all who buy it.
Craig Harrison BVM&S, Cert SAD,
MRCVS (UK)
BOOK REVIEWS
Diagnostic Ultrasound in Small
Animal Practice
Edited by Paddy Mannion
Blackwell Publishing Ltd.,(www.blackwellpublishing.com)338 pages, 339 Illustrations Paperback. ISBN 9780632053872
( € 56 approx) £39 99
EDITED BY
Paddy Mannion
This book is described in its introduction
as a replacement for Diagnostic Ultrasound in the Dog and Cat which in its
time was an extremely useful and accessible reference for anyone who had just
begun to work with diagnostic ultrasound
in these species. In the time since that
book was first published, the role, availability and capability of ultrasound has
widened dramatically to an extent that in
many practices ultrasonography is used
almost as frequently as radiography.
This replacement book manages to keep
the feel of accessibility of the earlier book.
It is multi author with contributions from
individuals who are well known in their
subject area. After three chapters on principles, artefacts and techniques the following five are devoted to the abdomen,
two on cardiac ultrasound and Doppler
and single chapters covering non-cardiac
thoracic ultrasound, the neck, eye and
orbit, musculoskeletal system and exotic
species. This division of the subject is natural and fits the manner in which clinical
patients are imaged. The arrangement of
each chapter follows a strict format and
although multi author there is a uniformity in layout, language style and depth of
coverage across the chapters. For each
organ or region, information is given under the heading technique and then normal appearance followed by abnormal
appearance. In describing abnormalities
the authors use two approaches; either a
description of abnormal appearance that
includes a suggested differential diagnosis
or mentioning specific diseases and giving
descriptions of ultrasonographic findings. Both approaches have merit. The
former because specific alterations in appearance are common to many diseases
and the latter because some (few) disease
process have specific changes or are com-
monly encountered in practice. Common
diseases present in a great variety of overlapping appearances and this is stressed
throughout the text. Almost every page
has clearly written text, a useful and informative ultrasound image paired with
a clear and simple explanatory line drawing. It makes for a book that is easy to
read. The wide use of text rather than
tables or bullet points allows the authors
to describe the significance and frequency
of findings and to generally engage the
reader. Each chapter concludes with a
short list of suggested further reading,
which typically comprises well chosen key
articles or textbook chapters.
There are few points to criticise in this
book. An area that is a little inconsistent
is seen in the figure legends. Many legends describe the scanning plain clearly in
the opening line. This is helpful and the
legends that do not have this information
are poorer as a result, especially to readers who are less familiar with ultrasound
100
and as a result will not immediately recognise the image orientation. The adrenal glands can be difficult to identify on
ultrasound and they are so in this book.
They appear to have been overlooked,
lost between the various chapters. This
is an unfortunate oversight as they are important and do cause a lot of frustration
for sonographers, first in finding them
and when found, in interpreting what
changes mean.
Notwithstanding any criticism, this book
has managed to achieve a difficult task.
It looks simple and is immediately useful
to anyone starting out with ultrasound
imaging. The depth of knowledge of the
various authors is such that the book is
not superficial and so makes stimulating
and interesting reading for individuals
who have many years ultrasound imaging
experience.
Fintan McEvoy MVB PhD DVR DipECVDI
MRCVS.(DK)
Calendar of main European National Meetings
and other continuing education opportunities
WSAVA & FECAVA Congresses (Red)
Principal annual meetings (blue)
A list of the addresses and telephone numbers of the Secretariat or person holding information is attached.
2007
11 April
ESFM
Birmingham
Feline Symposium, pre-BSAVA Congress
English
13-17 April
BSAVA
Birmingham
Annual Congress
English*
14 April
VÖK
Gmunden
CE Case Reports
German
14 April
CSAVA
Hradec Kralove
CE SA Anaesthesia
+ Nurses Dermatology
Czech
18-22 April
VÖK
Oberlech
CE Neurology Seminar
German
27-29 April
NACAM
Amsterdam
Voorjaarsdagen
Dutch/ English and others
28 April
VÖK
Steyr
CE Sonography Workshop
German
3-5 May
SVK/ASMPA
Montreux
Annual Congress
German/ French/English
4 May
BSAVA
Cambridge
CE All you need to know about Controlling
seizures
English
5 May
VÖK
Steyr
German
6 May
AIVPA-AVIEC
Sarzana SP
CE Clinical approach to Liver Pathology in the
dog
Italian
11-13 May
GSAVA
Goettingen
CE Soft tissue surgery
German /English
12-13 May
PSAVA
Warszawa
Annual Congress -Neurology
Polish/English
19-20 May
AIVPAFE
Parma-Facolta
Feline Ultrasonograpy and Ultrasound
Italian
19-20 May
BSAVA
Northampton
CE Medicine and imaging of the urinary tract
English
19-20 May
VÖK
Vienna
“Clinical Updates for Veterinarians”
German
21-25 May
ESAVS
Halmstad (S)
Dentistry III
English
26-27 May
SAVAB
Antwerp
Obesity Seminar
English/ Dutch
2-3 June
ESAVA
Tallinn
CE Dentistry - FECAVA sponsored
English
15 June
BSAVA
Basingstoke
CE Lameness – A practical approach
English
17-20 June
ESVCE
Riccione (I)
Annual Meeting + International Veterinary
Behaviour Meeting
English
25th June-6 July
ESAVS
Toulouse(F)
Ophthalmology II
English
28-30 June
ECVS
Dublin (IRL)
Annual Scientific Meeting
English
9-20 July
Date TBA
ESAVS
Vienna(A)
Berne (CH)
Dermatology II
Diagnostic Ultrasound II
English
6-17 August
ESAVS
Vienna(A)
Dermatology III
English
20-24 August
ESAVS
Berne (CH)
Emergency and Critical Care II
English
26-29 August
WSAVA
Sydney (Aust)
World Congress
English and others
29 August-1 Sept
EAVDI Contact:
patsikm@vet.
auth.gr
Thessaloniki (GR)
Annual Meeting of the European Association
of Veterinary Diagnostic Imaging
www.symvoli.gr/eavdi 2007
English
30 August- 3
September
ESAVS
Vienna(A)
Soft tissue surgery
English
1 September
VÖK
Steyr
German
3-7 September
ESAVS
Zurich (CH)
Feline Medicine and Surgery III
English
3-7 September
ESAVS
Luxembourg
Cardiology I
English
5 September
BSAVA
BSAVA HQ Gloucester
CE Farm animal emergencies for Vets
English
6-10 September
ESAVS
Berne (CH)
Neurology II
English
7-9 September
ESVOT
Munich (D)
Wetlabs
English
13-15 September
ECVIM-CA
Budapest (H)
Annual Congress
English
13-15 September
ESVD/ECVD
Mainz (D)
Annual Congress
English
13-15 seprember
EVDS
Th Hague (NL)
Annual Congress
English
English
Italian
13-17 September
ESAVS
Berne (CH)
Neurology III /Neurosurgery
16 September
AIVPA/ SITOV
Mestre-Venice
Joint and soft tissue peri-articular surgery
21 September
BSAVA
York
CE Essentials in Ophthalmology
English
22 September
BSAVA
York
CE Latest Development in Ophthalmology
English
17-21 September
ESAVS
Brno (CS)
Exotic Pets Medicine and Surgery
English
17-21 September
ESAVS
Berne (CH)
Neuropathology Intensive course
English
20-24 September
ESAVS
Berne (CH)
Neurology I
English
101
21st-23rd
September
GSAVA
Duisburg
CE The Asthenic dog
German /English
21-23 September
ESFM
Progve (CS)
Annual Feline Congress
English
22-23 September
VÖK
Salzburg
Annual Congress
German/English
27-29 September
ESVN
Berne (CH)
20th Anniversary Annual Congress
English
29 September
VÖK
Steyr
German
1-5 October
ESAVS
Giessen (D)
Endoscopy Intensive Course
English
3-5 October
ESAVS
Halmstad (S)
Dentistry 1
English
12 – 14 October
SASAP
Belgrade
National Symposium – SIVEMAP 2007
English/Serbian
13-14 October
AIVPA
Modena
National Congress-Neurology Note: on the
12th PRECONGRESS DAY, IVDAO (Alternative
medicine), SITOV (Orthopaedics),and AIVPAFE
(Feline Medicine) will hold meetings
Italian
16 October
BSAVA
Gloucester BSAVA HQ
CE Liver Disease – not always bad news
English
English
19 October
BSAVA
Prestbury Cheshire
CE Is it infectious, immune or neoplastic
19-20 October
AVEPA
Barcelona
National Congress
Spanish/English
20 October
VÖK
Vienna
CE Patella Seminar
German
20-21 October
AIVPA/AIVPAFE
Perugia-Facolta
Ematology and cytology in the dog and cat
Italian
27-28th October
CSAVA
Hradec Kralove
Annual congress
English/Czech
1-3 November
TSAVA
Istanbul
Annual Congress
Turkish/English
8 November
BSAVA
Bristol
CE Pain and Anaesthesia Workshop
English
10-11 November
DSAVA
Aarhus
Annual Meeting
Danish/English
10-11November
VÖK
Baden
CE Oncology Seminar
German/English
11 November
AIVPA-SITOV
Torino
Tibial Wedge Osteotomy (TWO)
Italian
13 November
BSAVA
Knutsford
CE Getting off the fence, decision making in
Cardiology
English
15 November
BSAVA
Basingstoke
CE Getting off the fence, decision making in
Cardiology
English
15-18 November
GSAVA
Berlin
53rd Annual Congress
German/English
German
17-18 November
VÖK
Steyr
CE Sonography Seminar
19-30 November
ESAVS
Utrecht (NL)
Internal Medicine |||
English
6-9 December
AFVAC
Paris
Annual Congress
French
18 November
AIVPAFE
Lecce
Unknown fever in the cat
Italian
23 November
BSAVA
Gloucester BSAVA HQ
CE The Lab results say your pain is anaemic
– What next?
English
24-25 November
VÖK
Krems
CE Radiology Seminar
German
24-25 November
AIVPA/AIVPAFE
Torino
Radiology in the dog and cat
Italian
1 December
VÖK
Vienna
CE Emergency Cases
German
2 December
AIVPA/ISVRA
Caserta
Anaesthesiology
Italian
2008
3-6 April
BSAVA
Birmingham
Annual Congress
English*
24-26 April
NACAM
Amsterdam
Voorjaarsdagen
Dutch/ English and others
22-24 May
SVK/ASMPA
Interlaken
Annual Congress
German/French/English
10-12 July
ECVS
Basel (CH)
Annual Scientific Meeting
English
17th July
ECVS
Basel (CH)
Annual Scientific Meeting,
English
20-24 August
FECAVA/WSAVA/
VICAS
Dublin
14th FECAVA /32nd WSAVA/ SVK Congress
English/ and others
(26?) 2730November
AFVAC
Strasbourg
Anual Congress
French
* 60 Veterinary surgeons or 70 Nurse registrations required for simultaneous translation to be provided
ADVANCE NOTICE
2009
Voorjaarsdagen 23-25 April
2010
FECAVA/WSAVA/SVK Geneva 2-5 June
FECAVA/AFVAC/SAVAB/LAK 26-29 November Lille
BSAVA 2-5 April
102
Secretariat or address to contact for information
(Full Association names are given at the front of the Journal)
Contact Address for Information
Secretariat: 40 rue de Berri – F-75008 Paris
Segretariat: AIVPA - Viale dei Mille 140 - I-43100 Parma, Italy
Tel/Fax
Tel: (33) 1 53 83 91 60 – Fax: (33) 1 53 83 91 69
Tel: (39) 0521-290191 - Fax: (39) 0521-291314
Tel: +351 218 404 179 – Fax: +351 218 404 180
PSAVA
RSAVA
SAVAB
SkSAVA
Director: Dr. José H. Duarte Correia/ Secretariat: Rua Américo Durão,
18D, 1900-064 Lisboa, PORTUGAL
Secretariat: Paseo San Gervasio 46-48, E7E-08022 Barcelona
Director: Dr. Boyko Georgiev, Institute of Biology and Immunology
of Reproduction, Sofia 1113, Bulgaria
Contact: Dr. Josip, Krasni-Alipasina St. 37 7100 Sarajeva – Bosnia and
Herzegovina
Secretariat: Woodrow House 1 Telford Way, Waterwells Business Park
Quedgeley, Gloucester GB-GL2 AB
Director: Dr. Jiri Beranek, University of Veterinary and Pharmaceutical
Sciences – Palackého 1/3 – 612 Brno Czech Republic
Director: Dr. Davorin Lukman, Specijalizirana Ambulanta Varazdin
Trnovecka 6, 42000 Varazdin, Croatia
Secretariat: Emdrupvej 28 A, DK 2100 Copenhagen
Director: Dr. Tiina Toomet, Vabriku 45 4A Tallinn, EE- 10 41.Estonia
Director: Dr. Kaj Sittnikow, Ykskoivuntie 32, FIN-23500 Uusikaupunki
Secretariat: Dr. Birgit Leopold-Temmler, Gneisenaustr. 10, D- 30175
Hannover
Director: Fereac Biró, Isvan u. 2 Budapest H-1078
Director: Dr. Katerina Loukaki, Protopapa 29, Helioupolis, GR- 163 43
Athens
Secretary: Tom Angel, 28, rue de Syren – L-5870 Alzingen
Director: Dr. Lita Konopore, Zvaigznáju Gatve 2 Riga, LV-1082
Contact: Dr. Saulius Laurusevicius, Tilzes 18, LT-47181 Kaunas
Director: Marin Velicovski, Ul. Lazar Ppo Trajkov 5-7 Skopje, Fyrom
Director: Dr. C.L. Vella, Blue Cross Veterinary Clinic Msida Road,
Birkirkera, Malta
Secretariat: NACAM, PO box 421, 3990 GE, Houten, The Netherlands
Secretariat: SVF v/Dr. Ellef Blakstad, PO Box 6781 St. Olavs Plass N-0130
Oslo
Director: Dr Jerzy Gawor, Secretariat PSAVA 20-934, Lublin
Contact: Dr. A. Tkachov-Kuzmin, V-Kojinoi, 23 – 121096 Moscow, Russia
Director: Dr. J van Tilburg, Ernest Claeslaan 14 B-2500 Lier
Director: Dr. Igor Krampl, Sibirska 41, 83102 Bratislava, Slovak republic
SASAP
Director: Denis Novak, Dr Ivana Ribara 186/30, 11070 Belgrade, Serbia
Tel/fax: (381) 11 2851 923; (381) 11 382 17 12;
AFVAC
AIVPA
APMVEAC
AVEPA
BASAV
BHSAVA
BSAVA
CSAVA
CSAVS
DSAVA
ESAVA
FAVP
GSAVA
HSAVA
HVMS
LAK
LSAPS
LSAVA
MSAVA
MVA
NACAM
NSAVA
SSAVA
Director: Dr. Alexandra Vilén, Jönköping Small Animal Hospital
Oskarshallsgatan 6 – 8-553 03 Jönköping
SVK/ASMPA Director: Dr. Peter Sterchi, Mühlegrund – CH-3807 Iseltwald
SZVMZ
Director: Dr. Zorko Bojan, Veterinary Faculty, Gerbiceva 60, SLO-1000
Ljubljana, Slovenija
TSAVA
Director: Dr. Mustafa Aktas, University of Istanbul- Faculty of Veterinary
Medecine, Dept. of surgery. Avcilar Campus. 34320-Avcilar/IstanbulTurkey
USAVA
Director: Dr. Vladimir Charkin, 8 Filatova str., Apartement 24, Odessa
65000, Ukraine
Tel: (34) 93 2531522 – Fax: (34) 93 4183979
Tel: (359) 888 272529 – Fax: (359) 2 866 44 50
E-mail/Website
www.afvac.com
[email protected]
www.aivpa.it
[email protected]
www.apmveac.pt
www. avepa.es
[email protected]
[email protected]
Tel: (44) 1452 726700 – Fax: (44) 1452 726701
Tel: (420) 603 272 796 – Fax: (420) 549246974
[email protected]
www.bsava.com
[email protected]
Tel/Fax: (385) 42 331 895
[email protected]
Tel: (45) 38 71 08 88 – Fax: (45) 38 71 03 22
Tel: (372) 6413 11 – Fax: (372) 641 3110
Tel: (358) 2 844 2580 Fax: (358) 2 844 2589
Tel: (49)511-85 80 60 0r 99 Fax : (49)511-85 80 45
[email protected]
[email protected]
[email protected] *
[email protected]
Tel: (36) 305950750
Tel/Fax: (30) 2109932295
[email protected]
[email protected]
Tel: (352) 36 9807– Fax: (352) 36 9807
Tel: (371) 7546 366 – Fax: (371) 7606 202
Tel: (370) 698 45876 - Fax: (370) 373 63490
Tel: (389) 91 115 125 – Fax: (389) 91 114 619
Tel: (356) 225 363 – Fax: (356) 238 105
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
Tel : (31) 18 23 07 489 or Tel : (31) 6 20 89 44 71
Tel: (47) 22 994600 – Fax: (47) 22 994601
[email protected]
[email protected]
Tel: (81) 44 56 158
Tel/Fax: (7) 095 921 6376
Tel: (32) 3 489 2309 – Fax: (32) 3 480 1942
Tel: ( 421) 905 511971
Tel: (46) 36 34 18 80 Fax: (46) 36 34 18 85
www.pslwmz.org.pl
[email protected]
[email protected]
[email protected]
www.savlmz.org
[email protected]
www.smasap.org.yu
[email protected]
Tel: (41) 33 845 11 45
Tel: (386) 14779277 – Fax: (386) 647007111
[email protected]
[email protected]
Tel: 0212-4737070/17297 – Fax: 0212-4737240
[email protected]
www.tsava.org
v.charkin.hotmail.com or
[email protected]
www.usava.org.va
VICAS
Director: Dr. Peter A. Murphy, Summerhill Veterinary Hospital, Wexford,
Tel: (353) 5391 43185 – Fax: (353) 5391 43185
[email protected]
Co. Wexford Ireland
by request
www.veterinary-ireland.org
VÖK
Director: Dr. Silvia Leugner, Schönbrunnerstraße 291/1/1/3, A-1120 Wien Tel. (43) 664/8212318 or (43) 1 8791669 - 18 or (43) [email protected]
1 8132983 - Fax (43) 1 8791669 - 33
[email protected] www.voek.at
Associate members
ESAVS
Contact: ESAVS Office Birkenfeld, Schadtengasse 2, D-55765 Birkenfeld Tel: (49) 6782 980650 – Fax: (49) 6782 4314
[email protected]
www.esavs.org
ECVD
Contact: Dr. Dominique Héripret, Clinique Vétérinaire Frégis 43, avenue
Tel: (33) 149 85 83 00 – Fax: (33) 149 85 83 01
[email protected]
Aristide-Briand F-94110 Arcueil
ECVS
Contact: Executive Secretary – ECVS Office Vetsuisse Faculty University
Tel: (41) 44 635 84 08 – Fax: (41) 44 313 03 8
[email protected]
Zürich Winterthurerstrasse 260, CH-8057 Zürich
www.ecvs.org
ESFM
Contact: Claire Bessant, Taeselbury, Highstreet, Tisbury, Wiltshire, GB
Tel: (44) 1747 871872 - Fax: (44) 1747 871873
[email protected] or
- SP3 6LD, UK
[email protected]
ESVC
Contact: Dr. Chris Amberger, 96, rue de la Servette CH-1202, Geneve
Tel: (41) 22 734.42.48 - Fax: (41) 22 733.97.06
[email protected]
www.esvc.ch
ESVCE
Contact: Dr. Sarah Heath, 10 Rushton, Upton, Chester GB-CH2 1RE
Tel: (44) 1244 377365 – Fax: (44) 1244 399288
[email protected].
co.uk or:
[email protected]
ESVD
ESVD Secretary, Dr Aiden P. Foster, VLA Shrewsbury, Kendal Road,
Tel +44 (0) 1743 467621 – Fax +44 (0)1743 441060 [email protected]
Harlescott, Shrewsbury, Shropshire, SY1 4HD
www. esvd.org
ESVIM
Tel: (+44) 141 330 5848 - Fax: +44 141 330 3663
Contact: Dr. Rory Bell, Department of Veterinary Clinical Studies
[email protected]
University of Glasgow, Bearsden, Glasgow, GB- G61 1QH
ECVIM-CA
For Congress: Sharon Green Avenue du Guéret 1 B-1300 Limal
Tel: (+32) 10 400 603 - Fax: +32 10 400 703
www.ecvimcongress.org
[email protected]
ESVN
Tel: (44 )141 330 5738 - Fax: (44) 141 330 3663
Contact: Dr. Jacques Penderis, Division of Companion Animal Sciences,
[email protected]
Faculty of Veterinary Medicine, University of Glasgow, Bearsden,
www.esvn.org
Glasgow,GB- G61 1QH
ESVOT
Contact: Dr. Aldo Vezzoni, via Massarotti 60/A, I-26100 Cremona
Tel: (39) 0 372 23451 - Fax: (39) 0 372 20074
www.esvot.org
EVDS
Tel: +33 2 40 68 78 09 (76 72) –
President: Olivier Gauthier – Unite de Chirurgie Anesthesie – Ecole
[email protected]
Nationale Veterinaire de Nantes – Atlanpole La Chantrerie – BP 40706
Fax: +33 2 40 68 77 73
– F-44307 Nantes cedex 3
EVSSAR
Contact: Dr Alain Fontbonne, Dept of Animal Reproduction The National
[email protected].
Veterinary College7, Avenue Général de Gaulle F-94700 Maisons-Alfort
104
Tel.: (380) 503369810 - Fax: (380) 482 606726

journal

Transcription

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